PRODUCTION OF GIBBERELLINS IN RECOMBINANT HOSTS
20190071474 ยท 2019-03-07
Inventors
- Esben Halkjaer Hansen (Frederiksberg, DK)
- Nina Nicoline Rasmussen (Hvidovre, DK)
- Michael Naesby (Basel, CH)
- Jane Dannow Dyekjaer (Copenhagen, DK)
- Simon Carlsen (Copenhagen, DK)
- Adam Matthew Takos (Valby, DK)
- Nicholas Ohler (Reinach, CH)
Cpc classification
C12N9/0071
CHEMISTRY; METALLURGY
C12N9/0073
CHEMISTRY; METALLURGY
International classification
Abstract
The invention relates to recombinant microorganisms and methods for producing gibberellin compounds and gibberellin precursors.
Claims
1. A recombinant host cell, comprising: (a) a recombinant gene encoding a first cytochrome P450 (P450) polypeptide; and/or (b) a recombinant gene encoding a 2-oxoglutarate-dependent dioxygenase (2-ODD) polypeptide and/or a second cytochrome P450 (P450) polypeptide; wherein the recombinant host cell is capable of producing a gibberellin precursor and/or a gibberellin compound.
2. The recombinant host cell of claim 1, wherein the gene encoding the first P450 polypeptide encodes a kaurenoic acid oxidase (KAO) polypeptide or a cytochrome P450 monooxygenase-1 (P450-1) polypeptide.
3. The recombinant host cell of claim 1 or 2, wherein the gene encoding the first P450 polypeptide comprises: (a) a gene encoding a kaurenoic acid oxidase (KAO1) polypeptide; (b) a gene encoding a kaurenoic acid oxidase (KAO2) polypeptide; (c) a gene encoding a kaurenoic acid oxidase (KAO3) polypeptide; (d) a gene encoding a kaurenoic acid oxidase (KAO4) polypeptide; (e) a gene encoding a kaurenoic acid oxidase (KAO5) polypeptide; (f) a gene encoding a kaurenoic acid oxidase (KAO6) polypeptide; (g) a gene encoding a kaurenoic acid oxidase (KAO9) polypeptide; (h) a gene encoding a kaurenoic acid oxidase (KAO10) polypeptide; (i) a gene encoding a kaurenoic acid oxidase (KAO11) polypeptide; (j) a gene encoding a cytochrome P450 monooxygenase-2 (P450-2) polypeptide; (k) a gene encoding a cytochrome P450 monooxygenase-3 (P450-3) polypeptide; (l) a gene encoding a cytochrome P-450 BJ-1 (CYP112) polypeptide; and/or (m) a gene encoding a gibberellin A13-oxidase (GA.sub.13ox) polypeptide.
4. The recombinant host cell of claim 3, wherein: (a) the KAO1 polypeptide comprises a KAO1 polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:90; (b) the KAO2 polypeptide comprises a KAO2 polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:88; (c) the KAO3 polypeptide comprises a KAO3 polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:146; (d) the KAO4 polypeptide comprises a KAO4 polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:74; (e) the KAO5 polypeptide comprises a KAO5 polypeptide having at least 60% sequence identity to the amino acid sequence set forth in SEQ ID NO:62; (f) the KAO6 polypeptide comprises a KAO6 polypeptide having at least 60% sequence identity to the amino acid sequence set forth in SEQ ID NO:60; (g) the KAO9 polypeptide comprises a KAO9 polypeptide having at least 70% sequence identity to the amino acid sequence set forth in SEQ ID NO:68; (h) the KAO10 polypeptide comprises a KAO10 polypeptide having at least 70% sequence identity to the amino acid sequence set forth in SEQ ID NO:58; (i) the KAO11 polypeptide comprises a KAO11 polypeptide having at least 65% sequence identity to the amino acid sequence set forth in SEQ ID NO:64; (j) the P450-2 polypeptide comprises a P450-2 polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:80; (k) the P450-3 polypeptide comprises a P450-3 polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:186; (l) the CYP112 polypeptide comprises a CYP112 polypeptide having at least 70% sequence identity to the amino acid sequence set forth in SEQ ID NOs: 4, 6, 8, 10, 124, or 128; or (m) the GA.sub.13ox polypeptide comprises a GA.sub.13ox polypeptide having at least 70% sequence identity to the amino acid sequence set forth in SEQ ID NO:98.
5. The recombinant host cell of claim 1, wherein the gene encoding the second P450 polypeptide comprises: (a) a P450-2 polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:80; (b) a P450-2 polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:233; (c) a P450-2 polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO 235; (d) a P450-2 polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:237; (e) a P450-2 polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:18; or (f) a CYP112 polypeptide having at least 70% sequence identity to the amino acid sequence set forth in SEQ ID NO:124.
6. The recombinant host cell of any one of claims 1-5 wherein the gene encoding the 2-ODD polypeptide comprises: (a) a gene encoding a desaturase (DES) polypeptide; (b) a gene encoding a gibberellin A7-oxidase (GA.sub.7ox) polypeptide; (c) a gene encoding a gibberellin A3-oxidase (GA.sub.3ox) polypeptide; or (d) a gene encoding a gibberellin A20-oxidase (GA.sub.20ox) polypeptide.
7. The recombinant host cell of claim 6, wherein: (a) the DES polypeptide comprises a DES polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:26; (b) the GA.sub.7ox polypeptide comprises a GA.sub.7ox polypeptide having 60% or greater sequence identity to the amino acid sequence set forth in SEQ ID NO:152; (c) the GA.sub.3ox polypeptide comprises a GA.sub.3ox polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:36, or SEQ ID NO:44; or (d) the GA.sub.20ox polypeptide comprises a GA.sub.20ox polypeptide having at least 70% sequence identity to the amino acid sequence set forth in SEQ ID NO:40 or SEQ ID NO:42.
8. A recombinant host cell, comprising: (a) a gene encoding a kaurenoic acid oxidase (KAO4) polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:74; (b) a gene encoding a desaturase (DES) polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:26; (c) a gene encoding a cytochrome P450 monooxygenase-2 (P450-2) polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:80; and (d) a gene encoding a cytochrome P450 monooxygenase-3 (P450-3) polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:186; wherein the recombinant host cell is capable of producing a gibberellin precursor and/or a gibberellin compound.
9. A recombinant host cell, comprising: (a) a gene encoding a kaurenoic acid oxidase (KAO4) polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:74; (b) a gene encoding a gibberellin A20-oxidase (GA.sub.20ox) polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:42; (c) a gene encoding a cytochrome P450 monooxygenase-3 (P450-3) polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO: 186; and (d) a gene encoding a desaturase (DES) polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:26; wherein the recombinant host cell is capable of producing a gibberellin precursor and/or a gibberellin compound.
10. A recombinant host cell, comprising a gene encoding a kaurenoic acid oxidase (KAO) polypeptide having at least 60% sequence identity to the amino acid sequence set forth in SEQ ID NO:62, SEQ ID NO:60, or SEQ ID NO:152, at least 70% sequence identity to the amino acid sequence set forth in SEQ ID NO:58 or SEQ ID NO:68, at least 65% sequence identity to the amino acid sequence set forth in SEQ ID NO:64, or at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:74; wherein the recombinant host cell is capable of producing gibberellin precursor and/or a gibberellin compound.
11. The recombinant host cell of claim 10, further comprising: (a) a gene encoding a gibberellin A20-oxidase (GA.sub.20ox) polypeptide having at least 70% sequence identity to the amino acid sequence set forth in SEQ ID NO:40; and (b) a gene encoding a gibberellin A13-oxidase (GA.sub.13ox) polypeptide having at least 70% sequence identity to the amino acid sequence set forth in SEQ ID NO:98.
12. A recombinant host cell, comprising: (a) a gene encoding a kaurenoic acid oxidase (KAO11) polypeptide having at least 65% sequence identity to the amino acid sequence set forth in SEQ ID NO:64; and (b) a gene encoding a cytochrome P-450 BJ-1 (CYP112) polypeptide having at least 70% sequence identity to the amino acid sequence set forth in SEQ ID NO:124; wherein the recombinant host cell is capable of producing a gibberellin precursor and/or a gibberellin compound.
13. A recombinant host cell, comprising: (a) a gene encoding a kaurenoic acid oxidase (KAO4) polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:74; and (b) a gene encoding a cytochrome P-450 BJ-1 (CYP112) polypeptide having at least 70% sequence identity to the amino acid sequence set forth in SEQ ID NO:124; wherein the recombinant host cell is capable of producing a gibberellin precursor and/or a gibberellin compound.
14. The recombinant host cell of any one of claims 1-13, further comprising: (a) a gene encoding a polypeptide capable of synthesizing geranylgeranyl pyrophosphate (GGPP) from farnesyl diphosphate (FPP) and isopentenyl diphosphate (IPP); (b) a gene encoding a polypeptide capable of synthesizing ent-copalyl diphosphate from GGPP; (c) a gene encoding a polypeptide capable of synthesizing ent-kaurene from ent-copalyl pyrophosphate; (d) a gene encoding a bifunctional polypeptide capable of synthesizing ent-copalyl diphosphate from GGPP and synthesizing ent-kaurene from ent-copalyl pyrophosphate; (e) a gene encoding a polypeptide capable of synthesizing ent-kaurenoic acid from ent-kaurene; (f) a gene encoding a cytochrome B5 polypeptide; (g) a gene encoding a polypeptide capable of reducing cytochrome B5 polypeptide; (h) a gene encoding a polypeptide capable of reducing cytochrome P450 complex; (i) a gene encoding a ferredoxin polypeptide; (j) a gene encoding a ferredoxin reductase polypeptide; and/or (k) an alcohol dehydrogenase (ADH) polypeptide capable of reducing a gibberellin intermediate.
15. The recombinant host cell of claim 14, wherein: (a) the polypeptide capable of synthesizing geranylgeranyl pyrophosphate (GGPP) from farnesyl diphosphate (FPP) and isopentenyl diphosphate (IPP) comprises a polypeptide having at least 70% sequence identity to the amino acid sequence set forth in SEQ ID NO:50, SEQ ID NO:134, or SEQ ID NO:178; (b) the polypeptide capable of synthesizing ent-copalyl diphosphate from GGPP comprises a polypeptide having at least 70% sequence identity to the amino acid sequence set forth in SEQ ID NO:38, SEQ ID NO:102, SEQ ID NO:104, SEQ ID NO:106, SEQ ID NO:108, or SEQ ID NO:180; (c) the polypeptide capable of synthesizing ent-kaurene from ent-copalyl pyrophosphate comprises a polypeptide having at least 70% sequence identity to the amino acid sequence set forth in SEQ ID NO:102 or SEQ ID NO:106; (d) the bifunctional polypeptide capable of synthesizing ent-copalyl diphosphate from GGPP and synthesizing ent-kaurene from ent-copalyl pyrophosphate comprises a CDPS-KS polypeptide having at least 70% sequence identity to the amino acid sequence set forth in SEQ ID NO:104; (e) the polypeptide capable of synthesizing ent-kaurenoic acid from ent-kaurene comprises a polypeptide having at least 70% sequence identity to the amino acid sequence set forth in SEQ ID NO:82, SEQ ID NO:164, SEQ ID NO:170, or SEQ ID NO:172; (f) the cytochrome B5 polypeptide comprises a cytochrome B5 polypeptide having at least 60% sequence identity to the amino acid sequence set forth in SEQ ID NO:160 or SEQ ID NO:239; (g) the cytochrome B5 reductase polypeptide comprises a cytochrome B5 reductase polypeptide having at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:2 or SEQ ID NO:241; (h) the polypeptide capable of reducing cytochrome P450 complex comprises a CPR reductase polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:48, SEQ ID NO:100, SEQ ID NO:140, SEQ ID NO:158, SEQ ID NO:168, SEQ ID NO:192 or SEQ ID NO:194; (i) the ferredoxin polypeptide comprises a ferredoxin polypeptide having at least 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:148; (j) the ferredoxin reductase polypeptide comprises a ferredoxin reductase polypeptide having at least 70% sequence identity to the amino acid sequence set forth in SEQ ID NO:150; and/or (k) the ADH polypeptide comprises an ADH polypeptide having at least 70% sequence identity to the amino acid sequence set forth in SEQ ID NO:116.
16. The recombinant host cell of any one of claims 1-15, further comprising: (a) a gene encoding an open reading frame (ORF) polypeptide; (b) a gene encoding an aldehyde dehydrogenase (AIdDH) polypeptide; (c) a gene encoding a myo-inositol transport protein ITR1 (smt) polypeptide; (d) a gene encoding an endoplasmic reticulum (ER) membrane polypeptide; and/or (e) a gene encoding a damage resistance protein 1 (DAP) polypeptide.
17. The recombinant host cell of claim 16, wherein: (a) the ORF polypeptide comprises an ORF polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:154 or SEQ ID NO:156; (b) the AIdDH polypeptide comprises an AIdDH polypeptide having at least 60% sequence identity to the amino acid sequence set forth in SEQ ID NO:202; (c) the smt polypeptide comprises an smt polypeptide having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:209; (d) the ER membrane polypeptide comprises an inheritance of cortical ER protein 2 (ICE2) polypeptide having at least 60% sequence identity to the amino acid sequence set forth in SEQ ID NO:206; and/or (e) the DAP polypeptide comprises a DAP polypeptide having at least 70% sequence identity to the amino acid sequence set forth in SEQ ID NO:213, SEQ ID NO:215, SEQ ID NO:217, or SEQ ID NO:224.
18. The recombinant host cell of any one of claims 1-17, wherein expression of the genes increases the portion of the gibberellin precursor and/or the gibberellin compound produced by the recombinant host cell by at least about 10%, 25%, 50%, 75%, 80%, 90%, 95%, 100% or more.
19. The recombinant host cell of any one of claims 1-18, wherein the gibberellin compound comprises GA.sub.1, GA.sub.3, GA.sub.4, GA.sub.5, GA.sub.7, GA.sub.9, GA.sub.12, GA.sub.13, GA.sub.14, GA.sub.15, GA.sub.19, GA.sub.20, GA.sub.24, GA.sub.25, GA.sub.36, GA.sub.37, GA.sub.44, GA.sub.53, or GA.sub.110.
20. The recombinant host cell of any one of claims 1-19, wherein the recombinant host comprises a plant cell, a mammalian cell, an insect cell, a fungal cell, an algal cell or a bacterial cell.
21. A method of producing a gibberellin precursor and/or a gibberellin compound in a cell culture, comprising growing the recombinant host cell of any one of claims 1-20 in a cell culture, under conditions in which the genes are expressed; wherein the gibberellin precursor and/or the gibberellin compound is produced by the recombinant host cell.
22. The method of claim 21, further comprising isolating the gibberellin precursor and/or the gibberellin compound from the cell culture.
23. The method of claim 22, wherein the isolating step comprises: (a) contacting the cell culture comprising the gibberellin precursor and/or the gibberellin compound with: (i) one or more adsorbent resins in order to bind at least a portion of the gibberellin precursor and/or the gibberellin compound to the resin, thereby isolating the gibberellin precursor and/or the gibberellin compound; or (ii) one or more ion exchange or reversed-phase chromatography columns in order to bind at least a portion of the gibberellin precursor and/or the gibberellin compound in the column, thereby isolating the gibberellin precursor and/or the gibberellin compound; or (b) crystallizing and/or extracting the gibberellin precursor and/or the gibberellin compound from the cell culture, thereby isolating the gibberellin precursor and/or the gibberellin compound; or (c) separating the cell culture into a solid phase and a liquid phase, wherein the liquid phase comprises the gibberellin precursor and/or the gibberellin compound; and (i) contacting the liquid phase with one or more adsorbent resins in order to bind at least a portion of the gibberellin precursor and/or the gibberellin compound to the resin, thereby isolating the gibberellin precursor and/or the gibberellin compound; (ii) contacting the liquid phase with one or more ion exchange or reversed-phase chromatography columns in order to bind at least a portion of the gibberellin precursor and/or the gibberellin compound in the column, thereby isolating the gibberellin precursor and/or the gibberellin compound; or (iii) crystallizing and/or extracting the gibberellin precursor and/or the gibberellin compound from the liquid phase, thereby isolating the gibberellin precursor and/or the gibberellin compound.
24. The method of any one of claims 21-23, further comprising recovering the gibberellin precursor and/or the gibberellin compound.
25. The method of any one of claims 21-23, further comprising: (a) one or more steps of converting kaurenoic acid to GA.sub.12 and GA.sub.14 catalyzed by a first P450 polypeptide; and (b) a step of converting GA.sub.14 to GA.sub.4 catalyzed by a second P450 polypeptide.
26. The method of claim 25, wherein: (a) the first P450 polypeptide comprises: (i) a KAO4 polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:74; (ii) a KAO1 polypeptide having at least 50% sequence identity to the amino acid sequence set for in SEQ ID NO:90; or (iii) a KAO3 polypeptide having at least 50% sequence identity to the amino acid sequence set for in SEQ ID NO:146; and (b) the second P450 polypeptide comprises: (i) a P450-2 polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:80; (ii) a P450-2 polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:233; (iii) a P450-2 polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO 235; (iv) a P450-2 polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:237; (v) a P450-2 polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:18; or (vi) a CYP112 polypeptide having at least 70% sequence identity to the amino acid sequence set forth in SEQ ID NO:124.
27. The method of claim 25 or 26, further comprising a step of converting GA.sub.4 to GA.sub.1 catalyzed by a third P450 polypeptide.
28. The method of claim 27, wherein the third P450 polypeptide comprises: (a) a P450-3 polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:186; or (b) a GA.sub.13ox-1 polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:98.
29. The method of any one of claims 25-28, further comprising: (a) a step of converting GA.sub.4 to GA.sub.7 catalyzed by a 2-ODD polypeptide; and (b) a step of converting GA.sub.7 to GA.sub.3 catalyzed by a fourth P450 polypeptide.
30. The method of claim 29, wherein: (a) the 2-ODD polypeptide comprises a DES polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ IN NO:26; and (b) the fourth P450 polypeptide comprises: (i) a P450-3 polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:186; or (ii) a GA.sub.13ox-1 polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:98.
31. The method of any one of claims 20-26, further comprising: (a) one or more steps of converting kaurenoic acid to GA.sub.12 and/or GA.sub.14 catalyzed by a first P450 polypeptide; and (b) a step of converting GA.sub.14 to GA.sub.4 catalyzed by a 2-ODD polypeptide.
32. The method of claim 31, wherein: (a) the first P450 polypeptide comprises a KAO4 polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:74; and (b) the 2-ODD polypeptide comprises a GA.sub.20ox polypeptide having at least 70% sequence identity to the amino acid sequence set forth in SEQ ID NO:40 or SEQ ID NO:42.
33. The method of claim 31 or 32, further comprising a step of converting GA.sub.4 to GA.sub.1 catalyzed by a second P450 polypeptide.
34. The method of claim 33, wherein the second P450 polypeptide comprises: (a) a P450-3 polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:186; or (b) a GA.sub.13ox-1 polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:98.
35. The method of claim 31 or 32, further comprising: (a) a step of converting GA.sub.4 to GA.sub.7 catalyzed by a second 2-ODD polypeptide; and (b) a step of converting GA.sub.7 to GA.sub.3 catalyzed by a second P450 polypeptide.
36. The method of claim 35, wherein: (a) the second 2-ODD polypeptide comprises a DES polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:26; and (b) the second P450 polypeptide comprises: (i) a P450-3 polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:186; or (ii) a GA.sub.13ox-1 polypeptide having at least 50% sequence identity to the amino acid sequence set forth in SEQ ID NO:98.
37. The method of any one of claims 21-36, wherein the recombinant host cell is grown in a fermentor at a temperature for a period of time, wherein the temperature and period of time facilitate the production of the gibberellin precursor and/or the gibberellin compound.
38. The method of any one of claims 21-37, wherein the gibberellin compound comprises GA.sub.3 and its precursors, metabolites, or related compounds, including: GA.sub.1, GA.sub.4, GA.sub.5, GA.sub.7, GA.sub.9, GA.sub.12, GA.sub.13, GA.sub.14, GA.sub.15, GA.sub.19, GA.sub.20, GA.sub.24, GA.sub.25, GA.sub.36, GA.sub.37, GA.sub.44, GA.sub.53, or GA.sub.110.
39. The method of any one of claims 21-38, wherein the recombinant host comprises a plant cell, a mammalian cell, an insect cell, a fungal cell, an algal cell or a bacterial cell.
40. A cell culture, comprising the recombinant host cell of any one of claims 1-20, the cell culture further comprising: (a) the gibberellin precursor and/or the gibberellin compound produced by the recombinant host cell; (b) a carbon source; and (c) supplemental nutrients comprising trace metals, vitamins, salts, YNB, a nitrogen source, and/or amino acids; wherein one or more gibberellin precursors and/or the gibberellin compounds are present at a concentration of at least 100 mg/liter of the cell culture.
41. A cell lysate from the recombinant host cell of any one of claims 1-20 grown in the cell culture, comprising: (a) the gibberellin precursor and/or the gibberellin compound produced by the recombinant host cell; (b) a carbon source; and (c) supplemental nutrients comprising trace metals, vitamins, salts, YNB, a nitrogen source, and/or amino acids; wherein one or more gibberellin precursors and/or the gibberellin compounds are present at a concentration of at least 100 mg/liter of the cell culture.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0187] The following detailed description of the embodiments of the present invention can be best understood when read in conjunction with the following drawings, where like structure is indicated with like reference numerals and in which:
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DETAILED DESCRIPTION OF THE INVENTION
[0216] Before describing the present invention in detail, a number of terms will be defined. As used herein, the singular forms a, an, and the include plural referents unless the context clearly dictates otherwise. For example, reference to a nucleic acid means one or more nucleic acids.
[0217] It is noted that terms like preferably, commonly, and typically are not utilized herein to limit the scope of the claimed invention or to imply that certain features are critical, essential, or even important to the structure or function of the claimed invention. Rather, these terms are merely intended to highlight alternative or additional features that can or cannot be utilized in a particular embodiment of the present invention.
[0218] For the purposes of describing and defining the present invention it is noted that the term substantially is utilized herein to represent the inherent degree of uncertainty that can be attributed to any quantitative comparison, value, measurement, or other representation. The term substantially is also utilized herein to represent the degree by which a quantitative representation can vary from a stated reference without resulting in a change in the basic function of the subject matter at issue.
[0219] Methods well known to those skilled in the art can be used to construct genetic expression constructs and recombinant cells according to this invention. These methods include in vitro recombinant DNA techniques, synthetic techniques, in vivo recombination techniques, and polymerase chain reaction (PCR) techniques. See, for example, techniques as described in Green & Sambrook, 2012, MOLECULAR CLONING: A LABORATORY MANUAL, Fourth Edition, Cold Spring Harbor Laboratory, New York; Ausubel et al., 1989, CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, Greene Publishing Associates and Wiley Interscience, New York, and PCR Protocols: A Guide to Methods and Applications (Innis et al., 1990, Academic Press, San Diego, Calif.).
[0220] As used herein, the terms polynucleotide, nucleotide, oligonucleotide, and nucleic acid can be used interchangeably to refer to nucleic acid comprising DNA, RNA, derivatives thereof, or combinations thereof, in either single-stranded or double-stranded embodiments depending on context as understood by the skilled worker.
[0221] As used herein, the terms microorganism, microorganism host, microorganism host cell, recombinant host, and recombinant host cell can be used interchangeably. As used herein, the term recombinant host is intended to refer to a host, the genome of which has been augmented by at least one DNA sequence. The term transformant(s) is intended to refer a host to which at least one DNA sequence has been introduced. Such DNA sequences for recombinant host and transformant(s) include but are not limited to genes that are not naturally present, DNA sequences that are not normally transcribed into RNA or translated into a protein (expressed), and other genes or DNA sequences which one desires to introduce into a host. It will be appreciated that typically the genome of a recombinant host described herein is augmented through stable introduction of one or more recombinant genes. Generally, introduced DNA is not originally resident in the host that is the recipient of the DNA, but it is within the scope of this disclosure to isolate a DNA segment from a given host, and to subsequently introduce one or more additional copies of that DNA into the same host, e.g., to enhance production of the product of a gene or alter the expression pattern of a gene. In some instances, the introduced DNA will modify or even replace an endogenous gene or DNA sequence by, e.g., homologous recombination or site-directed mutagenesis. Suitable recombinant hosts include microorganisms, for example bacteria, fungi or yeast.
[0222] As used herein, the term recombinant gene refers to a gene or DNA sequence that is introduced into a recipient host, regardless of whether the same or a similar gene or DNA sequence may already be present in such a host. Introduced, or augmented in this context, is known in the art to mean introduced or augmented by the hand of man. Thus, a recombinant gene can be a DNA sequence from another species or can be a DNA sequence that originated from or is present in the same species but has been incorporated into a host by recombinant methods to form a recombinant host. It will be appreciated that a recombinant gene that is introduced into a host can be identical to a DNA sequence that is normally present in the host being transformed, and is introduced to provide one or more additional copies of the DNA to thereby permit overexpression or modified expression of the gene product of that DNA. In some aspects, said recombinant genes are encoded by cDNA. In other embodiments, recombinant genes are synthetic and/or codon-optimized for expression in Saccharomyces cerevisiae (S. cerevisiae).
[0223] As used herein, the term engineered biosynthetic pathway refers to a biosynthetic pathway that occurs in a recombinant host, as described herein. In some aspects, one or more steps of the biosynthetic pathway do not naturally occur in an unmodified host. In some embodiments, a heterologous version of a gene is introduced into a host that comprises an endogenous version of the gene.
[0224] As used herein, the term endogenous gene refers to a gene that originates from and is produced or synthesized within a particular organism, tissue, or cell. In some embodiments, the endogenous gene is a yeast gene. In some embodiments, the gene is endogenous to S. cerevisiae, including, but not limited to S. cerevisiae strain S288C. In some embodiments, an endogenous yeast gene is overexpressed. As used herein, the term overexpress is used to refer to the expression of a gene in an organism at levels higher than the level of gene expression in a wild type organism. In some embodiments, an endogenous yeast gene, for example ADH, is deleted. As used herein, the terms deletion, deleted, knockout, and knocked out can be used interchangeably to refer to an endogenous gene that has been manipulated to no longer be expressed in an organism, including, but not limited to, S. cerevisiae.
[0225] As used herein, the terms heterologous sequence and heterologous coding sequence are used to describe a sequence derived from a species other than the recombinant host. In some embodiments, the recombinant host is an S. cerevisiae cell, and a heterologous sequence is derived from an organism other than S. cerevisiae. A heterologous coding sequence, for example, can be from a prokaryotic microorganism, a eukaryotic microorganism, a plant, an animal, an insect, or a fungus different than the recombinant host expressing the heterologous sequence. In some embodiments, a coding sequence is a sequence that is native to the host.
[0226] A selectable marker can be one of any number of genes that complement host cell auxotrophy, provide antibiotic resistance, or result in a color change. Non-limiting examples of a selectable marker can include a URA3 marker and a NatMx maker. Linearized DNA fragments of the gene replacement vector then are introduced into the cells using methods well known in the art. Integration of the linear fragments into the genome and the disruption of the gene can be determined based on the selection marker and can be verified by, for example, PCR or Southern blot analysis. Subsequent to its use in selection, a selectable marker can be removed from the genome of the host cell by, e.g., Cre-LoxP systems (see e.g., U.S. 2006/0014264). Alternatively, a gene replacement vector can be constructed in such a way as to include a portion of the gene to be disrupted, where the portion is devoid of any endogenous gene promoter sequence and encodes none, or an inactive fragment of, the coding sequence of the gene.
[0227] As used herein, the terms variant and mutant are used to describe a protein sequence that has been modified at one or more amino acids, compared to the wild-type sequence of a particular protein.
[0228] As used herein, the term inactive fragment is a fragment of the gene that encodes a protein having, e.g., less than about 10% (e.g., less than about 9%, less than about 8%, less than about 7%, less than about 6%, less than about 5%, less than about 4%, less than about 3%, less than about 2%, less than about 1%, or 0%) of the activity of the protein produced from the full-length coding sequence of the gene. Such a portion of a gene is inserted in a vector in such a way that no known promoter sequence is operably linked to the gene sequence, but that a stop codon and a transcription termination sequence are operably linked to the portion of the gene sequence. This vector can be subsequently linearized in the portion of the gene sequence and transformed into a cell. By way of single homologous recombination, this linearized vector is then integrated in the endogenous counterpart of the gene with inactivation thereof.
[0229] As used herein, the term gibberellin refers to a diterpene plant hormone having the structure of the molecule shown in Formula I and
##STR00001##
TABLE-US-00001 TABLE 1 Gibberellin structure. R.sup.1 R.sup.2 R.sup.3 R.sup.4 R.sup.10 R.sup.8 GA.sub.1 -OH OC10 OC19 OH GA.sub.3 C2 C1 -OH OC10 OC19 OH GA.sub.4 -OH OC10 OC19 GA.sub.5 C3 C2 OC10 OC19 OH GA.sub.7 C2 C1 -OH OC10 OC19 GA.sub.9 OC10 OC19 GA.sub.12 OH CH.sub.3 GA.sub.14 -OH OH CH.sub.3 GA.sub.15 OH CH.sub.2OH open lactone GA.sub.15 OCH.sub.2C10 CH.sub.2OC19 GA.sub.19 OH CHO OH GA.sub.20 OC10 OC19 OH GA.sub.24 OH CHO GA.sub.44 OCH.sub.2C10 CH.sub.2OC19 OH GA.sub.53 OH CH.sub.3 OH R.sup.5 = OH, R.sup.12 = CH.sub.3, all other R = H
[0230] As used herein, the term gibberellin precursor refers to intermediate compounds in a gibberellin biosynthetic pathway. Gibberellin precursors include, but are not limited to, GGPP, ent-copalyl-diphosphate, ent-kaurene, ent-kaurenoic acid, and ent-kaurenoic acid-7--OH kaurenoic acid. See, e.g.,
[0231] In some aspects, gibberellins and gibberellin precursors are accumulated in an ent-kaurenoic acid-producing host. Recombinant ent-kaurenoic acid-producing and terpene-producing Saccharomyces cerevisiae (S. cerevisiae) strains are described in WO 2011/153378, WO 2013/022989, WO 2014/122227, and WO 2014/122328, each of which has been incorporated by reference herein in its entirety. Methods of producing terpenes in recombinant hosts, by whole cell bio-conversion, and in vitro are also described in WO 2011/153378, WO 2013/022989, WO 2014/122227, and WO 2014/122328.
[0232] In some embodiments, gibberellins and/or gibberellin precursors are produced in vivo through expression of one or more enzymes involved in a gibberellin biosynthetic pathway in a recombinant host. For example, an ent-kaurenoic acid-producing recombinant host expressing one or more of a gene encoding a cytochrome P450 (P450) monooxygenase polypeptide, a gene encoding a cytochrome P450 reductase (CPR) polypeptide, and a gene a 2-ODD polypeptide can accumulate a gibberellin or gibberellin precursor in vivo. See, e.g.,
[0233] In some embodiments, gibberellins and/or gibberellin precursors are produced through contact of a gibberellin precursor with one or more enzymes involved in the gibberellin pathway in vitro. For example, contacting GA.sub.7 with a cytochrome P450 polypeptide can result in production of GA.sub.3 in vitro. In some embodiments, a gibberellin is produced through contact of a gibberellin precursor with one or more enzymes involved in the gibberellin pathway in vitro. For example, contacting ent-kaurene with a KO enzyme can result in production of ent-kaurenoic acid in vitro.
[0234] In some embodiments, a gibberellin or gibberellin precursor is produced by whole cell bioconversion. For whole cell bioconversion to occur, a host cell expressing one or more enzymes involved in the gibberellin pathway takes up and modifies a gibberellin precursor in the cell; following modification (e.g., addition of a double bond or oxidation) in vivo, a gibberellin remains in the cell and/or diffuses or is excreted into the culture medium. For example, a host cell expressing a gene encoding a cytochrome P450 monooxygenase polypeptide can take up GA.sub.7 and oxidize C13 of GA.sub.7 in the cell; following such a modification in vivo, GA.sub.3 can be excreted into the culture medium. In some embodiments, the cell can be permeabilized to take up a substrate to be modified or to excrete a modified product.
[0235] In some embodiments, one or more gibberellin precursors and/or one or more gibberellins are produced by co-culturing of two or more hosts. In some embodiments, one or more hosts, each expressing one or more enzymes involved in the gibberellin pathway, produce one or more gibberellin precursors and/or one or more gibberellins. For example, a host comprising a GGPPS, an CDPS, and/or a KO and a host comprising a cytochrome P450 monooxygenase, a cytochrome P450 reductase, and/or a 2-ODD produce one or more gibberellins.
[0236] In some aspects, a host comprises a heterologous gene encoding a GGPPS polypeptide. In some embodiments, the GGPPS polypeptide is a GGPPS polypeptide having the amino acid sequence set forth in SEQ ID NO:50, SEQ ID NO:134, or SEQ ID NO:178. The GGPPS polypeptide can catalyze conversion of farnesyl diphosphate (FPP) to GGPP.
[0237] In some aspects, a host comprises a heterologous gene encoding a CDPS polypeptide. In some embodiments, the CDPS polypeptide is a CDPS polypeptide having the amino acid sequence set forth in SEQ ID NO:102, SEQ ID NO:106, SEQ ID NO:108, or SEQ ID NO:180 or a bi-functional a CDPS polypeptide having the amino acid sequence set forth in SEQ ID NO:104, SEQ ID NO:227 or SEQ ID NO:229. The CDPS polypeptide can catalyze conversion of GGPP to ent-copalyl pyrophosphate. In some embodiments, the bi-functional CDPS polypeptide of SEQ ID NO:104 further comprises a P571S and/or L654P substitution. In some embodiments, a host comprising the mutant CDPS polypeptide accumulates greater levels of gibberellins, as compared to a host that does not comprise a gene encoding a mutant CDPS polypeptide.
[0238] In some aspects, a host comprises a heterologous gene encoding a KS polypeptide. In some embodiments, the KS polypeptide is a KS polypeptide having the amino acid sequence set forth in SEQ ID NO:102 or SEQ ID NO:106. The KS polypeptide can catalyze conversion of ent-copalyl pyrophosphate to ent-kaurene.
[0239] In some aspects, a host comprises a heterologous gene encoding a KO polypeptide. In some embodiments, the KO polypeptide is a KO polypeptide having the amino acid sequence set forth in SEQ ID NO:82, SEQ ID NO:164, SEQ ID NO:170, or SEQ ID NO:172. The KO polypeptide can catalyze conversion of ent-kaurene to ent-kaurenoic acid.
[0240] In some aspects, a host comprises a gene encoding a KAO polypeptide. The KAO polypeptide can be a plant-derived KAO polypeptide. In some embodiments, the KAO polypeptide is a KAO polypeptide having the amino acid sequence set forth in SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:74, SEQ ID NO:88, SEQ ID NO:90, or SEQ ID NO:146. The KAO polypeptide can catalyze, for example, conversion of ent-kaurenoic acid to ent-7-OH kaurenoic acid, ent-7-OH kaurenoic acid to GA.sub.12 aldehyde, GA.sub.12 aldehyde to GA.sub.12, and GA.sub.12 aldehyde to GA.sub.14 aldehyde. See, e.g.,
[0241] In some embodiments, a cytochrome B5 polypeptide (i.e., a cytochrome B5 polypeptide of SEQ ID NO:160) and/or a cytochrome B5 reductase polypeptide (i.e., a cytochrome B5 reductase polypeptide of SEQ ID NO:2) increases activity of a KAO polypeptide and/or a cytochrome P450 polypeptide. In some aspects, increased activity of a KAO polypeptide is evidenced by increased levels of GA.sub.14 and GA.sub.3 in an S. cerevisiae strain comprising a gene encoding a cytochrome B5 polypeptide and a gene encoding a cytochrome b5 reductase polypeptide. See Example 2 and
[0242] In some aspects, a host comprises a gene encoding a P450-1 polypeptide. The P450-1 polypeptide can be a fungus-derived P450-1 polypeptide. In some embodiments, the P450-1 polypeptide is a P450-1 polypeptide having the amino acid sequence set forth in SEQ ID NO:74, SEQ ID NO:88, SEQ ID NO:90, or SEQ ID NO:146. The P450-1 polypeptide can catalyze conversion of ent-kaurenoic acid to ent-7-OH kaurenoic acid, ent-7-OH kaurenoic acid to GA.sub.12 aldehyde, and GA.sub.12 aldehyde to GA.sub.14 aldehyde. In some aspects, a P450-1 polypeptide can have KAO and GA.sub.3ox activity. See Example 8. The fungal KAO enzymes (e.g., S. manihoticola KAO4 polypeptide (SEQ ID NO:73, SEQ ID NO:74) and G. fujikuroi KAO1 polypeptide (SEQ ID NO:89, SEQ ID NO:90) also have GA.sub.3ox activity.
[0243] In some aspects, a host comprises a gene encoding a GA 20-oxidase (GA.sub.20ox) polypeptide. The GA.sub.20ox polypeptide can be a plant-derived GA.sub.20ox polypeptide. In some embodiments, the GA.sub.20ox polypeptide comprises a GA.sub.20ox polypeptide having the amino acid sequence set forth in SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:40, or SEQ ID NO:42. The GA.sub.20ox polypeptide is a 2-ODD polypeptide and can catalyze conversion of GA.sub.14 to GA.sub.4, GA.sub.12 to GA.sub.15, GA.sub.24 to GA.sub.9, GA.sub.53 to GA.sub.44, and GA.sub.44 to GA.sub.19. See
[0244] In other embodiments, a host comprises a GA 7-oxidase (GA.sub.7ox) and/or a GA 3-oxidase (GA.sub.3ox). GA.sub.7ox and GA.sub.3ox polypeptides can be plant-derived 2-ODD polypeptides. In some embodiments, the GA.sub.7ox polypeptide comprises a GA.sub.7ox polypeptide having the amino acid sequence set forth in SEQ ID NO:16 or SEQ ID NO:162. In some embodiments, the GA.sub.3ox polypeptide comprises a GA.sub.3ox polypeptide having the amino acid sequence set forth in SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:36, or SEQ ID NO:44.
[0245] In some embodiments, a host comprises a GA 13-oxidase (GA.sub.13ox). A GA.sub.13ox polypeptide can be a plant-derived GA.sub.13ox polypeptide. In some embodiments, the GA.sub.13ox polypeptide comprises a GA.sub.13ox polypeptide having the amino acid sequence set forth in SEQ ID NO:72, SEQ ID NO:78, or SEQ ID NO:98. In some embodiments, a cytochrome B5 polypeptide (i.e., a cytochrome B5 polypeptide of SEQ ID NO:160) and/or a cytochrome B5 reductase polypeptide (i.e., a cytochrome B5 reductase polypeptide of SEQ ID NO:2) increases activity of a GA.sub.13ox polypeptide. In some embodiments, the GA.sub.13ox polypeptide can catalyze conversion of GA.sub.9 to GA.sub.20. See
[0246] In some aspects, a host comprises a gene encoding a P450-2 polypeptide. The P450-2 polypeptide can be a fungus-derived P450-2 polypeptide. In some embodiments, the P450-2 polypeptide comprises a P450-2 polypeptide having the amino acid sequence set forth in SEQ ID NO:14, SEQ ID NO:18, SEQ ID NO:70, SEQ ID NO:80, SEQ ID NO:94, SEQ ID NO:142, SEQ ID NO:233, SEQ ID NO:235, or SEQ ID NO:237. The P450-2 polypeptide can catalyze conversion of GA.sub.14 to GA.sub.4 and conversion of GA.sub.12 to GA.sub.9. See
[0247] In some aspects, a host comprises a gene encoding a P450-3 polypeptide. The P450-3 polypeptide can be a fungus-derived P450-3 polypeptide. In some embodiments, the P450-3 polypeptide comprises a P450-3 polypeptide having the amino acid sequence set forth in SEQ ID NO:46, SEQ ID NO:144, SEQ ID NO:184, or SEQ ID NO:186. The P450-3 polypeptide can catalyze conversion of GA.sub.4 to GA.sub.1 or GA.sub.7 to GA.sub.3. See
[0248] In some embodiments, a host comprises a gene encoding a GA.sub.4 desaturase (DES) polypeptide. The DES polypeptide can be a fungus-derived DES polypeptide. In some embodiments, the DES polypeptide comprises a DES polypeptide having the amino acid sequence set forth in SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, or SEQ ID NO:26. In some aspects, the DES polypeptide of SEQ ID NO:22 and/or the DES polypeptide of SEQ ID NO:26 comprises an L233P substitution. The DES polypeptide is a 2-ODD polypeptide and can catalyze conversion of GA.sub.4 to GA.sub.7. See
[0249] In some embodiments, a host comprises a gene encoding a cytochrome B5 polypeptide and/or a gene encoding a cytochrome B5 reductase polypeptide. In some aspects, a cytochrome B5 reductase provides electrons to a P450 monooxygenase through cytochrome B5. In some aspects, the cytochrome B5 electron transport system assists a cytochrome P450 reductase by supplying an electron of the catalytic cycle or by acting as an allosteric activator. See, e.g., Troncoso et al., 2008, Phytochemistry 69(3):672-83. In some embodiments, the cytochrome B5 polypeptide comprises a cytochrome B5 polypeptide having the amino acid sequence set forth in SEQ ID NO:160. In some embodiments, the cytochrome B5 reductase polypeptide comprises a cytochrome B5 polypeptide having the amino acid sequence set forth in SEQ ID NO:2. See Example 2.
[0250] In some embodiments, a host comprises a CYP112 polypeptide. In some embodiments, the CYP112 polypeptide comprises a CYP112 polypeptide having the amino acid sequence set forth in SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:124, or SEQ ID NO:128. The CYP112 polypeptide can catalyze conversion of GA.sub.12 to GA.sub.15, GA.sub.15 to GA.sub.24, GA.sub.24 to GA.sub.9, and GA.sub.14 to GA.sub.4. See
[0251] In some embodiments, a host comprises one or more heterologous genes encoding one or more alcohol dehydrogenase (ADH) polypeptides. The ADH polypeptide can be an ADH polypeptide having the amino acid sequence set forth in SEQ ID NO:112, SEQ ID NO:116, or SEQ ID NO:118. See
[0252] In some embodiments, a host comprising CDPS-KS bifunctional polypeptides can be comparatively tested in a host inserted with CytB5-1 and CytB5red-1. The host may then be transformed with CPR12 (SEQ ID NO:167 which encodes SEQ ID NO:168), RsKO_GA (SEQ ID NO:169 which encodes SEQ ID NO:170), GGPPS7 (SEQ ID NO:176 and SEQ ID NO:178), KO1 (SEQ ID NO:171 which encodes SEQ ID NO:172), and either CDPS-KS6+KS5 (SEQ ID NO:101 which encodes SEQ ID NO:102; and SEQ ID NO:181 which encodes SEQ ID NO:182), CDPS-KS6 (SEQ ID NO:101 which encodes SEQ ID NO:102), CDPS-KS4 (SEQ ID NO:226 which encodes SEQ ID NO:227), or CDPS-KS9 (SEQ ID NO 228 which encodes SEQ ID NO:229). See Example 3 and Table 6. In some aspects, the CDPS-KS activity converts GGPPS to kaurenoic acid.
[0253] In some embodiments, a host may comprise KO1 (SEQ ID NO:171 (nt) and SEQ ID NO:172 (aa) and CPR19 (SEQ ID NO:193 (nt) and SEQ ID NO:194 (aa)) and may be transformed with CDPS-KS6 (SEQ ID NO:101), KS5 (SEQ ID NO:181), GGPPS7 (SEQ ID NO:177), KO1 (SEQ ID NO:171), KAO and CPR genes using USER based DNA assembler vectors and NatMx marker. The host may co-express KAO-3/CPR19 polypeptides (SEQ ID NO:230 and SEQ ID NO:193), KAO-4/CPR17 (SEQ ID NO:73 and SEQ ID NO:187) or CPR19 (SEQ ID NO:193) polypeptides, or KAO-5/CPR12 (SEQ ID NO:61 and SEQ ID NO:167) or CPR19 polypeptides (for example, SEQ ID NO:193). See Example 4,
[0254] In some embodiments, a host may comprise FfCytB5-1 (SEQ ID NO:159 (nt) and SEQ ID NO:160 (aa)), FfCytB5red-1 (SEQ ID NO:01 (nt) and SEQ ID NO:02 (aa)), CPR19 (SEQ ID NO:193 (nt) and SEQ ID NO:194 (aa)), RsKO-GA (SEQ ID NO:169 (nt) and SEQ ID NO:170 (aa)), KS5 (SEQ ID NO:181 (nt) and SEQ ID NO:182 (aa)), tCDPS5 (SEQ ID NO:179 (nt) and SEQ ID NO:180 (aa)), GGPPS-7 (SEQ ID NO:177 (nt) and SEQ ID NO:178 (aa)), and KO1 (SEQ ID NO:171 (nt) and SEQ ID NO:172 (aa)) and be transformed with P450-3-1 (SEQ ID NO:45), P450-2-4 (SEQ ID NO:141), P450-3-4 (SEQ ID NO:185), DES-1 (SEQ ID NO:25), and either KAO1 (SEQ ID NO:89), KAO3 (SEQ ID NO:145), KAO4 (SEQ ID NO:73) or KAO5 (SEQ ID NO:61). See Example 4,
[0255] In some embodiments, a host may be inserted with P450-3-4 (SEQ ID NO:141(nt) and SEQ ID NO:142 (aa)), KO1 (SEQ ID NO:170 (nt) and SEQ ID NO:171 (aa)), GGPPS-7 (SEQ ID NO:177 (nt) and SEQ ID NO:178 (aa)), CDPS-KS6 (SEQ ID NO:101 (nt) and SEQ ID NO:102 (aa)), KAO4 (SEQ ID NO:73 (nt) and SEQ ID NO:74 (aa)), FfCytB5-1 (SEQ ID NO:159 (nt) and SEQ ID NO:160 (aa)), CPR1 (SEQ ID NO:165 (nt) and SEQ ID NO:166 (aa)), CPR19 (SEQ ID NO:193 (nt) and SEQ ID NO:194 (aa)), and various P450-2 genes: P450-2-1 (SEQ ID NO:79 (nt) and SEQ ID NO:80 (aa)), P450-2-8 (SEQ ID NO:232 (nt) and SEQ ID NO:233 (aa)), P450-2-9 (SEQ ID NO:234 (nt) and SEQ ID NO:235 (aa)), and P450-2-10 (SEQ ID NO:236 (nt) and SEQ ID NO:237 (aa)). See Example 5, Table 9, and
[0256] In some embodiments, P450-2 genes may be introduced by integration into a host using a USER cloning based vector system using the URA3 selection marker. P450-2 genes integrated may be selected from SEQ ID NO:13, SEQ ID NO:17, SEQ ID NO:80, and SEQ ID NO:141. See Example 5, Table 10, and
[0257] In some embodiments, an S. cerevisiae strain (strain N) comprising a gene encoding a truncated CDPS polypeptide (SEQ ID NO:179, SEQ ID NO:180), a gene encoding a KS polypeptide (SEQ ID NO:181, SEQ ID NO:182), a first gene encoding a KO polypeptide (SEQ ID NO:171, SEQ ID NO:172), a second gene encoding a KO polypeptide (SEQ ID NO:169, SEQ ID NO:170), a gene encoding a CPR polypeptide (SEQ ID NO:167, SEQ ID NO:168), a gene encoding an ERG20-GGPPS7 polypeptide (SEQ ID NO:195, SEQ ID NO:196), a gene encoding a Gibberellin fujikuroi P450-2-1 polypeptide (SEQ ID NO:79, SEQ ID NO:80), a gene encoding a Gibberellin fujikuroi P450-3-4 polypeptide (SEQ ID NO:185, SEQ ID NO:186), a gene encoding an S. manihoticola KAO4 polypeptide (SEQ ID NO:73, SEQ ID NO:74), a gene encoding a G. fujikuroi DES-1 polypeptide (SEQ ID NO:25, SEQ ID NO:26), a gene encoding a G. fujikuroi cytochrome B5 polypeptide (SEQ ID NO:159, SEQ ID NO:160), and a gene encoding a G. fujikuroi cytochrome B5 reductase polypeptide (SEQ ID NO:1, SEQ ID NO:2) accumulate gibberellins, including, but not limited to, GA.sub.3, GA.sub.4, GA.sub.12, GA.sub.14, and GA.sub.17. See Example 2; Tables 2 and 4; and
[0258] In some embodiments, an S. cerevisiae strain (strain A) comprising a gene encoding a truncated CDPS polypeptide (SEQ ID NO:179, SEQ ID NO:180), a gene encoding a KS polypeptide (SEQ ID NO:181, SEQ ID NO:182), a first gene encoding a KO polypeptide (SEQ ID NO:171, SEQ ID NO:172), a second gene encoding a KO polypeptide (SEQ ID NO:169, SEQ ID NO:170), a gene encoding a CPR polypeptide (SEQ ID NO:167, SEQ ID NO:168), a gene encoding an ERG20-GGPPS7 polypeptide (SEQ ID NO:195, SEQ ID NO:196), a gene encoding a Gibberellin fujikuroi P450-2-1 polypeptide (SEQ ID NO:79, SEQ ID NO:80), a gene encoding a Gibberellin fujikuroi P450-3-4 polypeptide (SEQ ID NO:185, SEQ ID NO:186), a gene encoding an S. manihoticola KAO4 polypeptide (SEQ ID NO:73, SEQ ID NO:74), a gene encoding a G. fujikuroi DES-1 polypeptide (SEQ ID NO:25, SEQ ID NO:26), and a gene encoding an A. niger CPR12 polypeptide (SEQ ID NO:157, SEQ ID NO:158) accumulates gibberellins, including, but not limited to, GA.sub.3, GA.sub.4, GA.sub.12, GA.sub.13, GA.sub.14, GA.sub.25. See Example 2; Tables 3 and 4; and
[0259] In some embodiments, expression of ORF1 (SEQ ID NO:153, SEQ ID NO:154), ORF2 (SEQ ID NO:155, SEQ ID NO:156), AIdDH (SEQ ID NO:201, SEQ ID NO:202), ADH (SEQ ID NO:109, SEQ ID NO:110), ANK (SEQ ID NO:210, SEQ ID NO:225) and/or smt (SEQ ID NO:222, SEQ ID NO:209), which are clustered with various gibberellin pathway genes in G. fujikuroi, can improve turnover of gibberellin-producing S. cerevisiae strains described herein. See e.g., Bmke et al., 2009, Phytochemistry, 70(15-16):1876-93.
[0260] In some embodiments, an S. cerevisiae strain (strain F) comprising a gene encoding a truncated CDPS polypeptide (SEQ ID NO:179, SEQ ID NO:180), a gene encoding a KS polypeptide (SEQ ID NO:181, SEQ ID NO:182), a first gene encoding a KO polypeptide (SEQ ID NO:171, SEQ ID NO:172), a second gene encoding a KO polypeptide (SEQ ID NO:169, SEQ ID NO:170), a gene encoding a CPR polypeptide (SEQ ID NO:167, SEQ ID NO:168), a gene encoding an ERG20-GGPPS7 polypeptide (SEQ ID NO:195, SEQ ID NO:196), a gene encoding an A. thaliana GA.sub.20ox-4 polypeptide (SEQ ID NO:39, SEQ ID NO:40), a gene encoding a G. fujikuroi P450-3-4 polypeptide (SEQ ID NO:185, SEQ ID NO:186), a gene encoding an S. manihoticola KAO4 polypeptide (SEQ ID NO:73, SEQ ID NO:74), a gene encoding a G. fujikuroi DES-1 polypeptide (SEQ ID NO:25, SEQ ID NO:26), and a gene encoding an A. niger CPR16 polypeptide (SEQ ID NO:157, SEQ ID NO:158) accumulates gibberellins, including, but not limited to, GA.sub.3, GA.sub.4, GA.sub.12, and GA.sub.14. See Example 2,
[0261] In some embodiments, an S. cerevisiae strain comprising a gene encoding a truncated CDPS polypeptide (SEQ ID NO:179, SEQ ID NO:180), a gene encoding a KS polypeptide (SEQ ID NO:181, SEQ ID NO:182), a first gene encoding a KO polypeptide (SEQ ID NO:171, SEQ ID NO:172), a second gene encoding a KO polypeptide (SEQ ID NO:169, SEQ ID NO:170), a gene encoding a CPR polypeptide (SEQ ID NO:167, SEQ ID NO:168), a gene encoding an ERG20-GGPPS7 polypeptide (SEQ ID NO:195, SEQ ID NO:196), a gene encoding a C. maxima GA.sub.20ox-1 polypeptide (SEQ ID NO:39, SEQ ID NO:40), a gene encoding a G. fujikuroi P450-3-4 polypeptide (SEQ ID NO:185, SEQ ID NO:186), a gene encoding a G. fujikuroi DES-1 polypeptide (SEQ ID NO:25, SEQ ID NO:26), and a gene encoding an A. niger CPR16 polypeptide (SEQ ID NO:157, SEQ ID NO:158) accumulates gibberellins. See
[0262] In some embodiments, expression of a gene encoding a KAO polypeptide (such as, but not limited to, a KAO11 polypeptide having the amino acid sequence SEQ ID NO:64) in an ent-kaurenoic acid-producing S. cerevisiae strain that further coexpresses C. maxima GA.sub.20ox (SEQ ID NO:39, SEQ ID NO:40) and Oryza sativa GA.sub.13ox (SEQ ID NO:97, SEQ ID NO:98) results in accumulation of GA.sub.9 and GA.sub.20. See
[0263] In some embodiments, an S. cerevisiae strain (strain P) comprising a gene encoding a truncated CDPS polypeptide (SEQ ID NO:179, SEQ ID NO:180), a gene encoding a KS polypeptide (SEQ ID NO:181, SEQ ID NO:182), a first gene encoding a KO polypeptide (SEQ ID NO:171, SEQ ID NO:172), a second gene encoding a KO polypeptide (SEQ ID NO:169, SEQ ID NO:170), a gene encoding a CPR polypeptide (SEQ ID NO:167, SEQ ID NO:168), a gene encoding an ERG20-GGPPS7 polypeptide (SEQ ID NO:195, SEQ ID NO:196), a gene encoding a P. sativum KAO11 polypeptide (SEQ ID NO:63, SEQ ID NO:64), a gene encoding a C. maxima GA.sub.7ox polypeptide (SEQ ID NO:151, SEQ ID NO:152), a gene encoding a B. diazoefficiens ADH polypeptide (SEQ ID NO:115, SEQ ID NO:116), a gene encoding a B. diazoefficiens CYP112 polypeptide (SEQ ID NO:123, SEQ ID NO:124), a gene encoding a P. putida ferredoxin polypeptide (SEQ ID NO:147, SEQ ID NO:148), and a gene encoding a P. putida ferredoxin reductase polypeptide (SEQ ID NO:149, SEQ ID NO:150) accumulates GA.sub.9. See Example 7,
[0264] In some embodiments, an S. cerevisiae strain (strain U) comprising a gene encoding a truncated CDPS polypeptide (SEQ ID NO:179, SEQ ID NO:180), a gene encoding a KS polypeptide (SEQ ID NO:181, SEQ ID NO:182), a first gene encoding a KO polypeptide (SEQ ID NO:171, SEQ ID NO:172), a second gene encoding a KO polypeptide (SEQ ID NO:169, SEQ ID NO:170), a gene encoding a CPR polypeptide (SEQ ID NO:167, SEQ ID NO:168), a gene encoding an ERG20-GGPPS7 polypeptide (SEQ ID NO:195, SEQ ID NO:196), a gene encoding an S. manihoticola KAO4 polypeptide (SEQ ID NO:73, SEQ ID NO:74), a gene encoding a KO polypeptide (SEQ ID NO:169, SEQ ID NO:170), a gene encoding a B. diazoefficiens ADH polypeptide (SEQ ID NO:115, SEQ ID NO:116), a gene encoding a B. diazoefficiens CYP112 polypeptide (SEQ ID NO:123, SEQ ID NO:124), a gene encoding a P. putida ferredoxin polypeptide (SEQ ID NO:147, SEQ ID NO:148), and a gene encoding a P. putida ferredoxin reductase polypeptide (SEQ ID NO:149, SEQ ID NO:150) accumulates GA.sub.4. See Example 7,
[0265] In some embodiments, an S. cerevisiae strain comprising a gene encoding a DAP1-2 polypeptide (SEQ ID NO:212, SEQ ID NO:213), a gene encoding a CytB5-2 polypeptide (SEQ ID NO:238, SEQ ID NO:239), a gene encoding a CytB5red-4 polypeptide (SEQ ID NO:240, SEQ ID NO:241), a gene encoding a FfCytB5-1 polypeptide (SEQ ID NO:159, SEQ ID NO:160), a gene encoding a FfCytB5red-1 polypeptide (SEQ ID NO:01, SEQ ID NO:02), a gene encoding an KAO11 polypeptide (SEQ ID NO:63, SEQ ID NO:64), a gene encoding CPR12 polypeptide (SEQ ID NO:167, SEQ ID NO:168), a gene encoding a CDPS-KS6 polypeptide (SEQ ID NO:101, SEQ ID NO:102), a gene encoding a KS5 polypeptide (SEQ ID NO:181, SEQ ID NO:182), a gene encoding a GGPPS-7 polypeptide (SEQ ID NO:177, SEQ ID NO:178), a gene encoding a KO1 polypeptide (SEQ ID NO:171, SEQ ID NO:172), a gene encoding a O. sativa GA.sub.13ox-1 polypeptide (SEQ ID NO:97, SEQ ID NO:98) a gene encoding a C. maxima GA.sub.20ox-4 polypeptide (SEQ ID NO:39, SEQ ID NO:40), and a gene encoding a M. macrocarpus GA.sub.3ox-1 polypeptide (SEQ ID NO:27, SEQ ID NO:28). The strain produces GA.sub.4 and other gibberellin intermediates. See Example 12,
[0266] In some embodiments, an S. cerevisiae strain comprising a gene encoding a DAP1-2 polypeptide (SEQ ID NO:212, SEQ ID NO:213), a gene encoding an ICE2-2 polypeptide (SEQ ID NO:206, SEQ ID NO:206), a gene encoding a CDPS-KS6 polypeptide (SEQ ID NO:101, SEQ ID NO:102), a gene encoding a KS5 polypeptide (SEQ ID NO:181, SEQ ID NO:182), a gene encoding a FfCytB5-1 polypeptide (SEQ ID NO:159, SEQ ID NO:160) a gene encoding a FfCytB5red-1 polypeptide (SEQ ID NO:01, SEQ ID NO:02), a gene encoding an KAO3 polypeptide (SEQ ID NO:145, SEQ ID NO:146), a gene encoding a CPR19 polypeptide (SEQ ID NO:193, SEQ ID NO:194), a gene encoding CPR12 polypeptide (SEQ ID NO:167, SEQ ID NO:168), a gene encoding a RsKO polypeptide (SEQ ID NO:169, SEQ ID NO:170), a gene encoding a GGPPS-7 polypeptide (SEQ ID NO:177, SEQ ID NO:178), a gene encoding a KO1 polypeptide (SEQ ID NO:171, SEQ ID NO:172), a gene encoding a P450-2-1 polypeptide (SEQ ID NO:79, SEQ ID NO:80) a gene encoding a KAO4 polypeptide (SEQ ID NO:73, SEQ ID NO:74), and a gene encoding a DES-1 polypeptide (SEQ ID NO:25, SEQ ID NO:26). The strain produces GA.sub.3 and other gibberellin intermediates. See Example 11 and Tables 19 and 20.
[0267] In some aspects, a gibberellin-producing host or gibberellin precursor-producing host comprises a damage resistance protein 1 (DAP1) polypeptide. In some embodiments, the DAP1 polypeptide is a DAP1 polypeptide as set forth in GenBank Accession No. YPL170W (SEQ ID NO:223, SEQ ID NO:224). In some aspects, the DAP1 enzyme is a G. fujikuroi DAP1 polypeptide is a polypeptide having the amino acid sequence set forth in SEQ ID NO:215, SEQ ID NO:217, or SEQ ID NO:219 (encoded by a nucleotide sequence set forth in SEQ ID NO:214, SEQ ID NO:216, or SEQ ID NO:217, respectively). In some aspects, expression of a DAP polypeptide increases cytochrome P450 activity.
[0268] In some aspects, a gibberellin-producing host or gibberellin precursor-producing host comprises inheritance of cortical ER protein 2 (ICE2) polypeptide. In some aspects, the ICE2 polypeptide can be a G. fujikuroi ICE2 (SEQ ID NO:205, SEQ ID NO:206). In some aspects, ICE2 is overexpressed.
[0269] In some embodiments, one or more endogenous genes encoding one or more alcohol dehydrogenase polypeptides are disrupted in a host. In some aspects, an alcohol dehydrogenase is knocked out or disrupted individually or in combination with one or more additional alcohol dehydrogenases. In some aspects, disruption of an endogenous alcohol dehydrogenase prevents reduction of aldehyde pathway intermediates to their corresponding alcohols. For example, disruption of one or more alcohol dehydrogeases can prevent reduction of GA.sub.12-aldehyde, GA.sub.14-aldehyde, kaurenal, GA.sub.24, and/or GA.sub.36. In some aspects, disruption of an endogenous alcohol dehydrogenase results in an increased accumulation of gibberellins.
[0270] Gibberellin production can be detected and/or analyzed by techniques generally available to one skilled in the art, for example, but not limited to, LC-MS, thin layer chromatography (TLC), high-performance liquid chromatography (HPLC), ultraviolet visible spectroscopy/spectrophotometry (UV-Vis), mass spectrometry (MS), and nuclear magnetic resonance spectroscopy (NMR). In some aspects, GA.sub.3 accumulates at least 100 mg/liter in fed batch fermentation methods.
Functional Homologs
[0271] Functional homologs of the polypeptides described above are also suitable for use in producing gibberellins in a recombinant host. A functional homolog is a polypeptide that has sequence similarity to a reference polypeptide, and that carries out one or more of the biochemical or physiological function(s) of the reference polypeptide. A functional homolog and the reference polypeptide can be a natural occurring polypeptide, and the sequence similarity can be due to convergent or divergent evolutionary events. As such, functional homologs are sometimes designated in the literature as homologs, or orthologs, or paralogs. Variants of a naturally occurring functional homolog, such as polypeptides encoded by mutants of a wild type coding sequence, can themselves be functional homologs. Functional homologs can also be created via site-directed mutagenesis of the coding sequence for a polypeptide, or by combining domains from the coding sequences for different naturally-occurring polypeptides (domain swapping). Techniques for modifying genes encoding functional polypeptides described herein are known and include, inter alia, directed evolution techniques, site-directed mutagenesis techniques and random mutagenesis techniques, and can be useful to increase specific activity of a polypeptide, alter substrate specificity, alter expression levels, alter subcellular location, or modify polypeptide-polypeptide interactions in a desired manner. Such modified polypeptides are considered functional homologs. The term functional homolog is sometimes applied to the nucleic acid that encodes a functionally homologous polypeptide.
[0272] Functional homologs can be identified by analysis of nucleotide and polypeptide sequence alignments. For example, performing a query on a database of nucleotide or polypeptide sequences can identify homologs of gibberellin biosynthesis polypeptides. Sequence analysis can involve BLAST, Reciprocal BLAST, or PSI-BLAST analysis of non-redundant databases using a cytochrome P450 monooxygenase, cytochrome P450 reductase, and/or 2-ODD amino acid sequence as the reference sequence. Amino acid sequence is, in some instances, deduced from the nucleotide sequence. Those polypeptides in the database that have greater than 40% sequence identity are candidates for further evaluation for suitability as a gibberellin biosynthesis polypeptide. Amino acid sequence similarity allows for conservative amino acid substitutions, such as substitution of one hydrophobic residue for another or substitution of one polar residue for another. If desired, manual inspection of such candidates can be carried out in order to narrow the number of candidates to be further evaluated. Manual inspection can be performed by selecting those candidates that appear to have domains present in gibberellin biosynthesis polypeptides, e.g., conserved functional domains. In some embodiments, nucleic acids and polypeptides are identified from transcriptome data based on expression levels rather than by using BLAST analysis.
[0273] Conserved regions can be identified by locating a region within the primary amino acid sequence of a gibberellin biosynthesis polypeptide that is a repeated sequence, forms some secondary structure (e.g., helices and beta sheets), establishes positively or negatively charged domains, or represents a protein motif or domain. See, e.g., the Pfam web site describing consensus sequences for a variety of protein motifs and domains on the World Wide Web at sanger.ac.uk/Software/Pfam/ and pfam.janelia.org/. Conserved regions also can be determined by aligning sequences of the same or related polypeptides from closely related species. Closely related species preferably are from the same family. In some embodiments, alignment of sequences from two different species is adequate to identify such homologs.
[0274] Typically, polypeptides that exhibit at least about 40% amino acid sequence identity are useful to identify conserved regions. Conserved regions of related polypeptides exhibit at least 45% amino acid sequence identity (e.g., at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% amino acid sequence identity). In some embodiments, a conserved region exhibits at least 92%, 94%, 96%, 98%, or 99% amino acid sequence identity.
[0275] For example, polypeptides suitable for producing gibberellins in a recombinant host include functional homologs of cytochrome P450 monooxygenase, cytochrome P450 reductase, and/or 2-ODD. Methods to modify the substrate specificity of, for example, cytochrome P450 monooxygenase, cytochrome P450 reductase, and/or 2-ODD, are known to those skilled in the art, and include without limitation site-directed/rational mutagenesis approaches, random directed evolution approaches and combinations in which random mutagenesis/saturation techniques are performed near the active site of the enzyme. For example, see Osmani et al., 2009, Phytochemistry 70: 325-47.
[0276] A candidate sequence typically has a length that is from 80% to 200% of the length of the reference sequence, e.g., 82, 85, 87, 89, 90, 93, 95, 97, 99, 100, 105, 110, 115, 120, 130, 140, 150, 160, 170, 180, 190, or 200% of the length of the reference sequence. A functional homolog polypeptide typically has a length that is from 95% to 105% of the length of the reference sequence, e.g., 90, 93, 95, 97, 99, 100, 105, 110, 115, or 120% of the length of the reference sequence, or any range between. A percent (%) identity for any candidate nucleic acid or polypeptide relative to a reference nucleic acid or polypeptide can be determined as follows. A reference sequence (e.g., a nucleic acid sequence or the amino acid sequence described herein) is aligned to one or more candidate sequences using the computer program ClustalW (version 1.83, default parameters), which allows alignments of nucleic acid or polypeptide sequences to be carried out across their entire length (global alignment).
[0277] ClustalW calculates the best match between a reference and one or more candidate sequences, and aligns them so that identities, similarities and differences can be determined. Gaps of one or more residues can be inserted into a reference sequence, a candidate sequence, or both, to maximize sequence alignments. For fast pairwise alignment of nucleic acid sequences, the following default parameters are used: word size: 2; window size: 4; scoring method: % age; number of top diagonals: 4; and gap penalty: 5. For multiple alignment of nucleic acid sequences, the following parameters are used: gap opening penalty: 10.0; gap extension penalty: 5.0; and weight transitions: yes. For fast pairwise alignment of protein sequences, the following parameters are used: word size: 1; window size: 5; scoring method: % age; number of top diagonals: 5; gap penalty: 3. For multiple alignment of protein sequences, the following parameters are used: weight matrix: blosum; gap opening penalty: 10.0; gap extension penalty: 0.05; hydrophilic gaps: on; hydrophilic residues: Gly, Pro, Ser, Asn, Asp, Gin, Glu, Arg, and Lys; residue-specific gap penalties: on. The ClustalW output is a sequence alignment that reflects the relationship between sequences. ClustalW can be run, for example, at the Baylor College of Medicine Search Launcher site on the World Wide Web (searchlauncher.bcm.tmc.edu/multi-align/multi-align.html) and at the European Bioinformatics Institute site on the World Wide Web (ebi.ac.uk/clustalw).
[0278] To determine percent (%) identity of a candidate nucleic acid or amino acid sequence to a reference sequence, the sequences are aligned using ClustalW, the number of identical matches in the alignment is divided by the length of the reference sequence, and the result is multiplied by 100. It is noted that the % identity value can be rounded to the nearest tenth. For example, 78.11, 78.12, 78.13, and 78.14 are rounded down to 78.1, while 78.15, 78.16, 78.17, 78.18, and 78.19 are rounded up to 78.2.
[0279] The term % identity as used herein about amino acid sequences means the degree of identity in percent between two amino acid sequences obtained when using the Needleman-Wunsch algorithm as implemented in the Needle program of the EMBOSS package (EMBOSS: The European Molecular Biology Open Software Suite), preferably version 5.0.0 or later. The parameters used are gap open penalty of 10, gap extension penalty of 0.5, and the EBLOSUM62 (EMBOSS version of BLOSUM62) substitution matrix. The output of Needle labeled longest identity (obtained using the nobrief option) is used as the percent identity and is calculated as follows:
[(identical amino acid residues)/(Length of alignmenttotal number of gaps in alignment)]100
[0280] The protein sequences of the present invention can further be used as a query sequence to perform a search against sequence databases, for example to identify other family members or related sequences. Such searches can be performed using the BLAST programs. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information. BLASTP is used for amino acid sequences and BLASTN for nucleotide sequences. The BLAST program uses as defaults: [0281] Cost to open gap: default=5 for nucleotides/11 for proteins [0282] Cost to extend gap: default=2 for nucleotides/1 for proteins [0283] Penalty for nucleotide mismatch: default=3 [0284] Reward for nucleotide match: default=1 [0285] Expect value: default=10 [0286] Wordsize: default=11 for nucleotides/28 for megablast/3 for proteins
[0287] Furthermore the degree of local identity between the amino acid sequence query or nucleic acid sequence query and the retrieved homologous sequences is determined by the BLAST program. However only those sequence segments are compared that give a match above a certain threshold. Accordingly the program calculates the identity only for these matching segments. Therefore the identity calculated in this way is referred to as local identity.
[0288] It will be appreciated that functional cytochrome P450, cytochrome P450 monooxygenase, cytochrome P450 reductase, and/or 2-ODD proteins can include additional amino acids that are not involved in the enzymatic activities carried out by the enzymes. In some embodiments, cytochrome P450, cytochrome P450 monooxygenase, cytochrome P450 reductase, and/or 2-ODD proteins are fusion proteins. The terms chimera, fusion polypeptide, fusion protein, fusion enzyme, fusion construct, chimeric protein, chimeric polypeptide, chimeric construct, and chimeric enzyme can be used interchangeably herein to refer to polypeptides engineered through the joining of two or more genes that code for different polypeptides (i.e., a polypeptide operatively-linked to a different polypeptide). For example, a polypeptide encoded by a nucleic acid sequence containing a coding sequence from one nucleic acid molecule and the coding sequence from another nucleic acid molecule in which the coding sequences are in the same reading frame such that when the fusion construct is transcribed and translated in a host cell, the protein is produced containing the two proteins. The two molecules can be adjacent in the construct or separated by a linker polypeptide that contains, 1, 2, 3, or more, but typically fewer than 10, 9, 8, 7, or 6 amino acids. The protein product encoded by a fusion construct is referred to as a fusion polypeptide. A chimeric or fusion protein provided herein can include one or more For example, a non-limiting example of a fusion protein can include a CDPS gene fused to a KS gene to generate a CDPS-KS fusion protein when expressed. In some embodiments, a nucleic acid sequence encoding a cytochrome P450, cytochrome P450 monooxygenase, cytochrome P450 reductase, and/or 2-ODD polypeptide can include a tag sequence that encodes a tag designed to facilitate subsequent manipulation (e.g., to facilitate purification or detection), secretion, or localization of the encoded polypeptide. Tag sequences can be inserted in the nucleic acid sequence encoding the polypeptide such that the encoded tag is located at either the carboxyl or amino terminus of the polypeptide. Non-limiting examples of encoded tags include green fluorescent protein (GFP), human influenza hemagglutinin (HA), glutathione S transferase (GST), polyhistidine-tag (HIS tag), and Flag tag (Kodak, New Haven, Conn.). Other examples of tags include a chloroplast transit peptide, a mitochondrial transit peptide, an amyloplast peptide, signal peptide, or a secretion tag.
[0289] In some embodiments, a fusion protein is a protein altered by domain swapping. As used herein, the term domain swapping is used to describe the process of replacing a domain of a first protein with a domain of a second protein. In some embodiments, the domain of the first protein and the domain of the second protein are functionally identical or functionally similar. In some embodiments, the structure and/or sequence of the domain of the second protein differs from the structure and/or sequence of the domain of the first protein.
[0290] In some embodiments, a protein is a protein altered by circular permutation, which consists in the covalent attachment of the ends of a protein that would be opened elsewhere afterwards. Thus, the order of the sequence is altered without causing changes in the amino acids of the protein. In some embodiments, a targeted circular permutation can be produced, for example but not limited to, by designing a spacer to join the ends of the original protein. Once the spacer has been defined, there are several possibilities to generate permutations through generally accepted molecular biology techniques, for example but not limited to, by producing concatemers by means of PCR and subsequent amplification of specific permutations inside the concatemer or by amplifying discrete fragments of the protein to exchange to join them in a different order. The step of generating permutations can be followed by creating a circular gene by binding the fragment ends and cutting back at random, thus forming collections of permutations from a unique construct. In some embodiments, a polypeptide disclosed herein is altered by circular permutation.
Gibberellin Biosynthesis Nucleic Acids
[0291] A recombinant gene encoding a polypeptide described herein comprises the coding sequence for that polypeptide, operably linked in sense orientation to one or more regulatory regions suitable for expressing the polypeptide. Because many microorganisms are capable of expressing multiple gene products from a polycistronic mRNA, multiple polypeptides can be expressed under the control of a single regulatory region for those microorganisms, if desired. A coding sequence and a regulatory region are considered to be operably linked when the regulatory region and coding sequence are positioned so that the regulatory region is effective for regulating transcription or translation of the sequence. Typically, the translation initiation site of the translational reading frame of the coding sequence is positioned between one and about fifty nucleotides downstream of the regulatory region for a monocistronic gene.
[0292] In many cases, the coding sequence for a polypeptide described herein is identified in a species other than the recombinant host, i.e., is a heterologous nucleic acid. Thus, if the recombinant host is a microorganism, the coding sequence can be from other prokaryotic or eukaryotic microorganisms, from plants or from animals. In some case, however, the coding sequence is a sequence that is native to the host and is being reintroduced into that organism. A native sequence can often be distinguished from the naturally occurring sequence by the presence of non-natural sequences linked to the exogenous nucleic acid, e.g., non-native regulatory sequences flanking a native sequence in a recombinant nucleic acid construct. In addition, stably transformed exogenous nucleic acids may be introduced at positions other than the position where the native sequence is found or kept extrachromosomally in episomes.
[0293] As used herein, the term regulatory region refers to a nucleic acid having nucleotide sequences that influence transcription or translation initiation and rate, and stability and/or mobility of a transcription or translation product. Regulatory regions include, without limitation, promoter sequences, enhancer sequences, response elements, protein recognition sites, inducible elements, protein binding sequences, 5 and 3 untranslated regions (UTRs), transcriptional start sites, termination sequences, polyadenylation sequences, introns, and combinations thereof. A regulatory region typically comprises at least a core (basal) promoter. A regulatory region also may include at least one control element, such as an enhancer sequence, an upstream element or an upstream activation region (UAR). A regulatory region is operably linked to a coding sequence by positioning the regulatory region and the coding sequence so that the regulatory region is effective for regulating transcription or translation of the sequence. For example, to operably link a coding sequence and a promoter sequence, the translation initiation site of the translational reading frame of the coding sequence is typically positioned between one and about fifty nucleotides downstream of the promoter. A regulatory region can, however, be positioned as much as about 5,000 nucleotides upstream of the translation initiation site, or about 2,000 nucleotides upstream of the transcription start site.
[0294] The choice of regulatory regions to be included depends upon several factors, including, but not limited to, efficiency, selectability, inducibility, desired expression level, and preferential expression during certain culture stages. It is a routine matter for one of skill in the art to modulate the expression of a coding sequence by appropriately selecting and positioning regulatory regions relative to the coding sequence. It will be understood that more than one regulatory region may be present, e.g., introns, enhancers, upstream activation regions, transcription terminators, and inducible elements.
[0295] One or more genes can be combined in a recombinant nucleic acid construct in modules useful for a discrete aspect of gibberellin precursor and/or gibberellin production. Combining a plurality of genes in a module, particularly a polycistronic module, facilitates the use of the module in a variety of species. For example, a gibberellin biosynthesis gene cluster, or a UGT gene cluster, can be combined in a polycistronic module such that, after insertion of a suitable regulatory region, the module can be introduced into a wide variety of species. As another example, a UGT gene cluster can be combined such that each UGT coding sequence is operably linked to a separate regulatory region, to form a UGT module. Such a module can be used in those species for which monocistronic expression is necessary or desirable. In addition to genes useful for gibberellin precursor or gibberellin production, a recombinant construct typically also contains an origin of replication, and one or more selectable markers for maintenance of the construct in appropriate species.
[0296] It will be appreciated that because of the degeneracy of the genetic code, a number of nucleic acids can encode a particular polypeptide; i.e., for many amino acids, there is more than one nucleotide triplet that serves as the codon for the amino acid. Thus, codons in the coding sequence for a given polypeptide can be modified such that optimal expression in a particular host is obtained, using appropriate codon bias tables for that host (e.g., microorganism). As isolated nucleic acids, these modified sequences can exist as purified molecules and can be incorporated into a vector or a virus for use in constructing modules for recombinant nucleic acid constructs.
[0297] In some cases, it is desirable to inhibit one or more functions of an endogenous polypeptide in order to divert metabolic intermediates towards gibberellin precursor or gibberellin biosynthesis. For example, it may be desirable to downregulate synthesis of sterols in a yeast strain in order to further increase gibberellin precursor or gibberellin production, e.g., by downregulating squalene epoxidase. As another example, it may be desirable to inhibit degradative functions of certain endogenous gene products, e.g., glycohydrolases that remove glucose moieties from secondary metabolites or phosphatases as discussed herein. In such cases, a nucleic acid that overexpresses the polypeptide or gene product may be included in a recombinant construct that is transformed into the strain. Alternatively, mutagenesis can be used to generate mutants in genes for which it is desired to increase or enhance function.
Host Microorganisms
[0298] Recombinant hosts can be used to express polypeptides for the producing gibberellins, including mammalian, insect, plant, and algal cells. A number of prokaryotes and eukaryotes are also suitable for use in constructing the recombinant microorganisms described herein, e.g., gram-negative bacteria, yeast, and fungi. A species and strain selected for use as a gibberellin production strain is first analyzed to determine which production genes are endogenous to the strain and which genes are not present. Genes for which an endogenous counterpart is not present in the strain are advantageously assembled in one or more recombinant constructs, which are then transformed into the strain in order to supply the missing function(s).
[0299] In some embodiments, the bacterial cell comprises Escherichia cells, Lactobacillus cells, Lactococcus cells, Corynebacterium cells, Acetobacter cells, Acinetobacter cells, Pseudomonas cells, or Streptomyces cells.
[0300] In some embodiments, the fungal cell comprises a yeast cell. For example, the yeast cell can be a Saccharomycete. The yeast cell can comprise a cell from Saccharomyces cerevisiae, Schizosaccharomyces pombe, Yarrowia lipolytica, Candida glabrata, Ashbya gossypii, Cyberlindnera jadinii, Pichia pastoris, Kluyveromyces lactis, Hansenula polymorpha, Candida boidinii, Arxula adeninivorans, Xanthophyllomyces dendrorhous, or Candida albicans species. In an embodiment, the yeast cell is a cell from the Saccharomyces cerevisiae species. In another embodiment, the fungal cell of the fungal cell comprises a filamentous fungal cell.
[0301] Typically, the recombinant microorganism is grown in a fermenter at a temperature(s) for a period of time, wherein the temperature and period of time facilitate the production of a gibberellin precursor and/or gibberellin compound. For example, the period of time can be approximately 120 hours. Growth in a fermenter can be performed with agitation. The constructed and genetically engineered microorganisms provided by the invention can be cultivated using conventional fermentation processes, including, inter alia, chemostat, batch, fed-batch cultivations, semi-continuous fermentations such as draw and fill, continuous perfusion fermentation, and continuous perfusion cell culture. Depending on the particular microorganism used in the method, other recombinant genes such as isopentenyl biosynthesis genes and terpene synthase and cyclase genes may also be present and expressed. Levels of substrates and intermediates, e.g., isopentenyl diphosphate, dimethylallyl diphosphate, GGPP, ent-kaurene and ent-kaurenoic acid, can be determined by extracting samples from culture media for analysis according to published methods.
[0302] As used herein a carbon source or carbon sources can include any molecule that can be metabolized by a recombinant host cell to facilitate growth and/or production of the gibberellins. Examples of suitable carbon sources include, but are not limited to, sucrose (e.g., as found in molasses), fructose, xylose, ethanol, glycerol, glucose, cellulose, starch, cellobiose, maltodextrin, mannitol, other sugars or other glucose-comprising polymer. In embodiments employing yeast as a host, for example, carbons sources such as sucrose, fructose, xylose, ethanol, glycerol, and glucose are suitable. The carbon source can be provided to the host organism throughout the cultivation period or alternatively, the organism can be grown for a period of time in the presence of another energy source, e.g., protein, and then provided with a source of carbon only during the fed-batch phase.
[0303] After the recombinant microorganism has been grown in culture for the period of time, wherein the temperature and period of time facilitate the production of a gibberellin precursor and/or gibberellin compound, the gibberellin precursor and/or gibberellin compound can then be recovered from the culture using various techniques known in the art. In some embodiments, a permeabilizing agent can be added to aid the feedstock entering into the host and product getting out. For example, a crude lysate of the cultured microorganism can be centrifuged to obtain a supernatant. The resulting supernatant can then be applied to a chromatography column, e.g., a C-18 column, and washed with water to remove hydrophilic compounds, followed by elution of the compound(s) of interest with a solvent such as methanol. The compound(s) can then be further purified by preparative HPLC. See for example, WO 2009/140394.
[0304] It will be appreciated that the various genes and modules discussed herein can be present in two or more recombinant hosts rather than a single host. When a plurality of recombinant hosts is used, they can be grown in a mixed culture to accumulate gibberellin precursors and/or gibberellins.
[0305] Alternatively, the two or more hosts each can be grown in a separate culture medium and the product of the first culture medium, e.g., ent-kaurenoic acid, can be introduced into second culture medium to be converted into a subsequent intermediate, or into an end product such as, for example, GA.sub.3. The product produced by the second, or final host is then recovered. It will also be appreciated that in some embodiments, a recombinant host is grown using nutrient sources other than a culture medium and utilizing a system other than a fermenter.
[0306] Exemplary prokaryotic and eukaryotic species are described in more detail below. However, it will be appreciated that other species can be suitable. For example, suitable species can be in a genus such as Agaricus, Bacillus, Candida, Corynebacterium, Eremothecium, Escherichia, Bradyrhizobium, Rhizobium, Fusarium/Gibberella, Kluyveromyces, Laetiporus, Lentinus, Phaffia, Phanerochaete, Pichia, Physcomitrella, Rhodoturula, Saccharomyces, Schizosaccharomyces, Sphaceloma, Xanthophyllomyces or Yarrowia. Exemplary species from such genera include Lentinus tigrinus, Laetiporus sulphureus, Phanerochaete chrysosporium, Pichia pastoris, Cyberlindnera jadinii, Physcomitrella patens, Rhodoturula glutinis, Rhodoturula mucilaginosa, Phaffia rhodozyma, Bradyrhizobium japonicum, Xanthophyllomyces dendrorhous, F. fujikuroi/G. fujikuroi, Candida utilis, Candida glabrata, Candida albicans, and Yarrowia lipolytica.
[0307] In some embodiments, a microorganism can be a prokaryote such as Escherichia bacteria cells, for example, Escherichia coli cells; Lactobacillus bacteria cells; Lactococcus bacteria cells; Corynebacterium bacteria cells; Acetobacter bacteria cells; Acinetobacter bacteria cells; or Pseudomonas bacterial cells.
[0308] In some embodiments, a microorganism can be an Ascomycete such as G. fujikuroi, Kluyveromyces lactis, Schizosaccharomyces pombe, A. niger, Yarrowia lipolytica, Ashbya gossypii, or S. cerevisiae.
[0309] In some embodiments, a microorganism can be an algal cell such as Blakeslea trispora, Dunaliella salina, Haematococcus pluvialis, Chlorella sp., Undaria pinnatifida, Sargassum, Laminaria japonica, Scenedesmus almeriensis species.
[0310] In some embodiments, a microorganism can be a cyanobacterial cell such as Blakeslea trispora, Dunaliella salina, Haematococcus pluvialis, Chlorella sp., Undaria pinnatifida, Sargassum, Laminaria japonica, Scenedesmus almeriensis.
Saccharomyces spp.
[0311] Saccharomyces is a widely used organism in synthetic biology, and can be used as the recombinant microorganism platform. For example, there are libraries of mutants, plasmids, detailed computer models of metabolism and other information available for S. cerevisiae, allowing for rational design of various modules to enhance product yield. Methods are known for making recombinant microorganisms.
Aspergillus spp.
[0312] Aspergillus species such as A. oryzae, A. niger and A. sojae are widely used microorganisms in food production and can also be used as the recombinant microorganism platform. Nucleotide sequences are available for genomes of A. nidulans, A. fumigatus, A. oryzae, A. clavatus, A. flavus, A. niger, and A. terreus, allowing rational design and modification of endogenous pathways to enhance flux and increase product yield. Metabolic models have been developed for Aspergillus, as well as transcriptomic studies and proteomics studies. A. niger is cultured for the industrial production of a number of food ingredients such as citric acid and gluconic acid, and thus species such as A. niger are generally suitable for producing gibberellins. E. coli
[0313] E. coli, another widely-used organism in synthetic biology, can also be used as the recombinant microorganism platform. Similar to Saccharomyces, there are libraries of mutants, plasmids, detailed computer models of metabolism and other information available for E. coli, allowing for rational design of various modules to enhance product yield. Methods similar to those described above for Saccharomyces can be used to make recombinant E. coli microorganisms.
Agaricus, Gibberella, and Phanerochaete spp.
[0314] Agaricus, Gibberella, and Phanerochaete spp. can be useful because they are known to produce large amounts of isoprenoids in culture. Thus, the terpene precursors for producing large amounts of gibberellins are already produced by endogenous genes. Thus, modules comprising recombinant genes for gibberellin biosynthesis polypeptides can be introduced into species from such genera without the necessity of introducing mevalonate or MEP pathway genes.
Arxula adeninivorans (Blastobotrys adeninivorans)
[0315] Arxula adeninivorans is dimorphic yeast (it grows as budding yeast like the baker's yeast up to a temperature of 42 C., above this threshold it grows in a filamentous form) with unusual biochemical characteristics. It can grow on a wide range of substrates and can assimilate nitrate. It has successfully been applied to the generation of strains that can produce natural plastics or the development of a biosensor for estrogens in environmental samples.
Yarrowia lipolytica
[0316] Yarrowia lipolytica is dimorphic yeast (see Arxula adeninivorans) and belongs to the family Hemiascomycetes. The entire genome of Yarrowia lipolytica is known. Yarrowia species is aerobic and considered to be non-pathogenic. Yarrowia is efficient in using hydrophobic substrates (e.g. alkanes, fatty acids, oils) and can grow on sugars. It has a high potential for industrial applications and is an oleaginous microorganism. Yarrowia lipolyptica can accumulate lipid content to approximately 40% of its dry cell weight and is a model organism for lipid accumulation and remobilization. See e.g., Nicaud, 2012, Yeast 29(10):409-18; Beopoulos et al., 2009, Biochimie 91(6):692-6; Bankar et al., 2009, Appl Microbiol Biotechnol. 84(5):847-65.
Rhodotorula sp.
[0317] Rhodotorula is unicellular, pigmented yeast. The oleaginous red yeast, Rhodotorula glutinis, has been shown to produce lipids and carotenoids from crude glycerol (Saenge et al., 2011, Process Biochemistry 46(1):210-8). Rhodotorula toruloides strains have been shown to be an efficient fed-batch fermentation system for improved biomass and lipid productivity (Li et al., 2007, Enzyme and Microbial Technology 41:312-7).
Rhodosporidium toruloides
[0318] Rhodosporidium toruloides is oleaginous yeast and useful for engineering lipid-production pathways. See, e.g., Zhu et al., 2013, Nature Commun. 3:1112; Ageitos et al., 2011, Applied Microbiology and Biotechnology 90(4):1219-27).
Candida boidinii
[0319] Candida boidinii is methylotrophic yeast (it can grow on methanol). Like other methylotrophic species such as Hansenula polymorpha and Pichia pastoris, it provides an excellent platform for producing heterologous proteins. Yields in a multigram range of a secreted foreign protein have been reported. A computational method, IPRO, recently predicted mutations that experimentally switched the cofactor specificity of Candida boidinii xylose reductase from NADPH to NADH. See, e.g., Mattanovich et al., 2012, Methods Mol Biol. 824:329-58; Khoury et al., 2009, Protein Sci. 18(10):2125-38.
Hansenula polymorpha (Pichia angusta)
[0320] Hansenula polymorpha is methylotrophic yeast (see Candida boidinii). It can furthermore grow on a wide range of other substrates; it is thermo-tolerant and can assimilate nitrate (see also Kluyveromyces lactis). It has been applied to producing hepatitis B vaccines, insulin and interferon alpha-2a for the treatment of hepatitis C, furthermore to a range of technical enzymes. See, e.g., Xu et al., 2014, Virol Sin. 29(6):403-9.
Kluyveromyces lactis
[0321] Kluyveromyces lactis is yeast regularly applied to the production of kefir. It can grow on several sugars, most importantly on lactose which is present in milk and whey. It has successfully been applied among others for producing chymosin (an enzyme that is usually present in the stomach of calves) for producing cheese. Production takes place in fermenters on a 40,000 L scale. See, e.g., van Ooyen et al., 2006, FEMS Yeast Res. 6(3):381-92.
Pichia pastoris
[0322] Pichia pastoris is methylotrophic yeast (see Candida boidinii and Hansenula polymorpha). It provides an efficient platform for producing foreign proteins. Platform elements are available as a kit and it is worldwide used in academia for producing proteins. Strains have been engineered that can produce complex human N-glycan (yeast glycans are similar but not identical to those found in humans). See, e.g., Piirainen et al., 2014, N Biotechnol. 31(6):532-7.
Physcomitrella spp.
[0323] Physcomitrella mosses, when grown in suspension culture, have characteristics similar to yeast or other fungal cultures. This genera can be used for producing plant secondary metabolites, which can be difficult to produce in other types of cells.
[0324] It can be appreciated that the recombinant host cell disclosed herein can comprise a plant cell, a mammalian cell, an insect cell, a fungal cell, comprising a yeast cell, wherein the yeast cell is a cell from Saccharomyces cerevisiae, Schizosaccharomyces pombe, Yarrowia lipolytica, Candida glabrata, Ashbya gossypii, Cyberlindnera jadinii, Pichia pastoris, Kluyveromyces lactis, Hansenula polymorpha, Candida boidinii, Arxula adeninivorans, Xanthophyllomyces dendrorhous, or Candida albicans species or is a Saccharomycete or is a Saccharomyces cerevisiae cell, an algal cell or a bacterial cell, comprising Escherichia cells, Lactobacillus cells, Lactococcus cells, Cornebacterium cells, Acetobacter cells, Acinetobacter cells, or Pseudomonas cells.
Plants
[0325] Various plants can be used as recombinant host cells (e.g., plant cells, both monocotyledenous and dicotyledenous). In an embodiment, the plants or host cells used in the methods can be derived from monocots, particularly the members of the taxonomic family known as the Gramineae. This includes all members of the grass family of which the edible varieties are known as cereals. The cereals include a wide variety of species such as wheat (Triticum sps.), rice (Oryza sps.) barley (Hordeum sps.) oats, (Avena sps.) rye (Secale sps.), corn (maize) [Zea sps.) and millet (Pennisettum sps.). In another embodiment, the plants or host cells used can be derived from dicots (e.g., soybean (Glycine spp.)). In order to produce transgenic plants that produce gibberellins, plant cells or tissues derived from them are transformed or integrated with genes coding for various enzymes the result in the production of gibberellins. The transgenic plant cells are cultured in medium containing the appropriate selection agent to identify and select for plant cells which express the heterologous nucleic acid sequence. After plant cells that express the heterologous nucleic acid sequence are selected, whole plants can be regenerated from the selected transgenic plant cells. Techniques for regenerating whole plants from transformed plant cells are generally known in the art.
[0326] Plant cells or tissues can be transformed with expression constructs (i.e., heterologous nucleic acid constructs) using a variety of standard techniques. In some embodiments, the heterologous nucleic acid sequences can be stably integrated into the host cell genome so that the integrated nucleic acid sequences are passed onto successive plant generations. The skilled artisan will recognize that a wide variety of transformation techniques exist in the art. Any technique that is suitable for the target host plant may be employed. For example, the nucleic acid sequences can be introduced in a variety of forms including, but not limited to, as a strand of DNA, in a plasmid, or in an artificial chromosome. The introduction of the constructs into the target plant cells can be accomplished by a variety of techniques, including, but not limited to calcium-phosphate-DNA co-precipitation, electroporation, microinjection, Agrobacterium-mediated transformation, liposome-mediated transformation, protoplast fusion or microprojectile bombardment. When Agrobacterium is used for plant cell transformation, a vector is introduced into the Agrobacterium host for homologous recombination with T-DNA or the Ti- or Ri-plasmid present in the Agrobacterium host. The Ti- or Ri-plasmid containing the T-DNA for recombination may be armed (capable of causing gall formation) or disarmed (incapable of causing gall formation), the latter being permissible, so long as the vir genes are present in the transformed Agrobacterium host. The armed plasmid can give a mixture of normal plant cells and gall. In some embodiments, Agrobacterium can be used as the vehicle for transforming host plant cells. The expression or transcription construct bordered by the T-DNA border region(s) is inserted into a broad host range vector capable of replication in E. coli and Agrobacterium, for example pRK2 or derivatives thereof. Alternatively, one may insert the sequences to be expressed in plant cells into a vector containing separate replication sequences, one of which stabilizes the vector in E. coli, and the other in Agrobacterium. A number of markers have been developed for use with plant cells, such as resistance to chloramphenicol, kanamycin, the aminoglycoside G418, hygromycin, or the like.
[0327] It will be appreciated that the various genes and modules discussed herein can be present in two or more recombinant microorganisms rather than a single microorganism. When a plurality of recombinant microorganisms is used, they can be grown in a mixed culture to produce gibberellin precursors and/or gibberellins. For example, a first microorganism can comprise one or more biosynthesis genes for producing a gibberellin precursor, while a second microorganism comprises gibberellin biosynthesis genes. The product produced by the second, or final microorganism is then recovered. It will also be appreciated that in some embodiments, a recombinant microorganism is grown using nutrient sources other than a culture medium and utilizing a system other than a fermenter.
[0328] Alternatively, the two or more microorganisms each can be grown in a separate culture medium and the product of the first culture medium, e.g., ent-kaurenoic acid, can be introduced into second culture medium to be converted into a subsequent intermediate, or into an end product such as GA.sub.3. The product produced by the second, or final microorganism is then recovered.
Down Stream Processing
[0329] A number of different methods can be used to isolate and purify the gibberellin precursors and/or gibberellin compounds produced by the methods and host cells disclosed herein. For example, the isolating steps may comprise: (a) contacting the cell culture comprising the gibberellin precursor and/or the gibberellin compound with: (i) one or more adsorbent resins in a packed column in order to bind at least a portion of the gibberellin precursor and/or the gibberellin compound to the resin, thereby isolating the gibberellin precursor and/or the gibberellin compound; or (ii) one or more ion exchange or reversed-phase chromatography columns in order to bind at least a portion of the gibberellin precursor and/or the gibberellin compound in the column, thereby isolating the gibberellin precursor and/or the gibberellin compound; or (b) crystallizing and/or extracting the gibberellin precursor and/or the gibberellin compound from the cell culture, thereby isolating the gibberellin precursor and/or the gibberellin compound; or (c) separating the cell culture into a solid phase and a liquid phase, wherein the liquid phase comprises the gibberellin precursor and/or the gibberellin compound; and (i) contacting the liquid phase with one or more adsorbent resins in order to bind at least a portion of the gibberellin precursor and/or the gibberellin compound to the resin, thereby isolating the gibberellin precursor and/or the gibberellin compound; (ii) contacting the liquid phase with one or more ion exchange or reversed-phase chromatography columns in order to bind at least a portion of the gibberellin precursor and/or the gibberellin compound in the column, thereby isolating the gibberellin precursor and/or the gibberellin compound; or (iii) crystallizing and/or extracting the gibberellin precursor and/or the gibberellin compound from the liquid phase, thereby isolating the gibberellin precursor and/or the gibberellin compound.
[0330] In an embodiment, the isolating step can comprise, separating the solid phase from the liquid phase using a process comprising tangential flow filtration with diafiltration membranes to generate a permeate stream comprising the gibberellin precursor and/or the gibberellin compound, wherein the membranes used in the tangential flow filtration are ultrafiltration or nanofiltration membranes. In an embodiment, the permeate stream is extracted by an organic solvent which phase-separates from the aqueous phase to generate an extracted gibberellin product in the organic solvent
[0331] Optionally the permeate stream containing the gibberellin product could be concentrated by some combination of reverse osmosis, nanofiltration, and evaporation to produce a crystallized gibberellin precursor and/or the gibberellin compound.
[0332] The aqueous gibberellin-containing permeate or the concentrate can be extracted by an organic solvent which phase-separates from the aqueous phase. The pH of the aqueous phase is adjusted to less than 4.0, or less than 3.0, in order to protonate the gibberellin molecules and ensure they partition into the organic phase to a high degree. The solvent extraction could be performed in a counter-current extraction centrifuge such as a Podbelniak extractor, or in a counter-current extraction column such as a Karr or Scheibel column. This yields the gibberellin product in an organic solvent suitable for subsequent purification processing.
[0333] It will be understood that organic solvent extraction can be replaced with a series of process operations which yield a similar organic solution of gibberellins. The series of process operations would include (a) precipitation of gibberellins from the aqueous concentrate produced by addition of acid until pH is less than 4.0 or less than 3.0; (b) filtration and optionally water-washing of the resulting gibberellins-containing solids; and (c) dissolution of the filtered gibberellins-containing solids into an organic solvent suitable for purification processing.
[0334] Optionally the organic extract can be contacted with carbon to adsorb impurities and color bodies. Optionally the carbon contacting can be done by mixing carbon in the organic extract and filtering the carbon out of the resulting suspension, or by feeding the organic extract to a column or filter containing a fixed bed of carbon and collecting a purified effluent stream. The organic extract can be crystallized by concentrating the solution evaporatively. The resulting gibberellins product crystals can be filtered, washed, and dried to yield a high-purity gibberellins product.
[0335] The invention will be further described in the following examples, which do not limit the scope of the invention described in the claims.
EXAMPLES
[0336] The Examples that follow are illustrative of specific embodiments of the invention, and various uses thereof. They are set forth for explanatory purposes only, and are not to be taken as limiting the invention.
Example 1. LC-MS Analytical Procedures
[0337] Liquid chromatography-mass spectrometry (LC-MS) analyses were performed on Waters ACQUITY UPLC (Waters Corporation) with a Waters ACQUITY UPLC BEH C18 column (2.150 mm, 1.7 m particles, 130 pore size) equipped with a pre-column (2.15 mm, 1.7 m particles, 130 pore size) coupled to a Waters ACQUITY TQD triple quadropole mass spectrometer with electrospray ionization (ESI) operated in negative ionization mode. Compound separation was achieved using a gradient of the two mobile phases: phase A (water with 0.1% formic acid) and phase B (MeCN with 0.1% formic acid) were separated by increasing from 20% to 50% B between 0.3 to 2.0 minutes, increasing to 100% B at 2.01 minutes and holding 100% B for 0.6 minutes, and re-equilibrating for 0.6 minutes. The flow rate was 0.6 mL/min, and the column temperature was set at 55 C. Gibberellins were monitored using SIM (Single Ion Monitoring) and quantified by comparing against authentic standards.
Example 2. Engineering of Gibberellin-Producing S. Cerevisiae Strain
[0338] An ent-kaurenoic acid-producing S. cerevisiae strain comprising genes encoding a truncated copalyl diphosphate synthase (CDPS) polypeptide (SEQ ID NO:179 (nt), SEQ ID NO:180 (aa)), a kaurene synthase (KS) polypeptide (SEQ ID NO:181 (nt), SEQ ID NO:182 (aa)), a first KO polypeptide (SEQ ID NO:171 (nt), SEQ ID NO:172 (aa)), a second KO polypeptide (SEQ ID NO:169 (nt), SEQ ID NO:170 (aa)), a CPR polypeptide (SEQ ID NO:167 (nt), SEQ ID NO:168 (aa)), and an ERG20-GGPPS7 polypeptide (SEQ ID NO:195 (nt), SEQ ID NO:196 (aa)) was engineered to accumulate gibberellins. Strains A, N, and F were transformed into this ent-kaurenoic acid-producing strain background; the genes of Table 2 or Table 3 were introduced into the strain using the USER based yeast integration vector system. See, e.g., Mikkelsen et al., 2012, Metabolic Engineering 14:104-11. See also, the pathway described in
TABLE-US-00002 TABLE 2 Genes expressed in S. cerevisiae strain N. Gene 1 Gene 2 Gene 1 SEQ ID NOs Gene 2 SEQ ID NOs G. fujikuroi SEQ ID NO: G. fujikuroi SEQ ID NO: P450-2-1 79 (nt) P450-3-4 185 (nt) SEQ ID NO: SEQ ID NO: 80 (aa) 186 (aa) S. manihoticola SEQ ID NO: G. fujikuroi SEQ ID NO: KAO4 73 (nt) DES-1 25 (nt) SEQ ID NO: SEQ ID NO: 74 (aa) 26 (aa) G. fujikuroi SEQ ID NO: G. fujikuroi SEQ ID NO: Cytochrome B5 159 (nt) Cytochrome B5 1 (nt) SEQ ID NO: reductase SEQ ID NO: 160 (aa) 2 (aa)
TABLE-US-00003 TABLE 3 Genes expressed in S. cerevisiae strain A. Gene 1 Gene 2 Gene 1 SEQ ID NOs Gene 2 SEQ ID NOs G. fujikuroi SEQ ID NO: G. fujikuroi SEQ ID NO: P450-2-1 79 (nt) P450-3-4 185 (nt) SEQ ID NO: SEQ ID NO: 80 (aa) 186 (aa) S. manihoticola SEQ ID NO: G. fujikuroi SEQ ID NO: KAO4 73 (nt) DES-1 25 (nt) SEQ ID NO: SEQ ID NO: 74 (aa) 26 (aa) A. niger SEQ ID NO: CPR16 157 (nt) SEQ ID NO: 158 (aa)
[0339] Furthermore, the ent-kaurenoic acid-producing S. cerevisiae strain described above was also transformed with the genes of Table 4 using the USER cloning based yeast integration system to engineer strain F. See the pathway described in
TABLE-US-00004 TABLE 4 Genes expressed in S. cerevisiae strain F. Gene 1 Gene 2 Gene 1 SEQ ID NOs Gene 2 SEQ ID NOs C. maxima SEQ ID NO: G. fujikuroi SEQ ID NO: GA.sub.20ox-4 39 (nt) P450-3-4 185 (nt) SEQ ID NO: SEQ ID NO: 40 (aa) 186 (aa) S. manihoticola SEQ ID NO: G. fujikuroi SEQ ID NO: KAO4 73 (nt) DES-1 25 (nt) SEQ ID NO: SEQ ID NO: 74 (aa) 26 (aa) A. niger SEQ ID NO: CPR16 157 (nt) SEQ ID NO: 158 (aa)
[0340] Gibberellin accumulation was observed with these recombinant S. cerevisiae strains and was measured using one of two LC-MS methods. In the first method, LC-MS analysis was performed using a Waters ACQUITY I-class UPLC system fitted with a Waters ACQUITY UPLC BEH shield RP18 column (2.150 mm, 1.7 m particles, 130 pore size) equipped with an ACQUITY UPLC BEH C18 VanGuard pre-column (130 , 1.7 m, 2.1 mm5 mm) connected to a Waters Xevo SQ Detector 2 single quadrupole mass spectrometer equipped with an electrospray ionization (ESI) source. Compound separation was carried out using mobile phase of eluent B (ACN with 0.1% formic acid) and eluent A (water with 0.1% formic acid) using gradient separation. Quantification of gibberellins was performed by comparing obtained signals with authentic standards. Gibberellin accumulation was detected using single ion reaction (SIR) in negative ionization mode using the traces described in Table 5. In the second method, LC-MS analysis was performed using a Waters ACQUITY I-class UPLC system fitted with a Waters ACQUITY UPLC BEH shield RP18 column (2.150 mm, 1.7 m particles, 130 pore size) equipped with an ACQUITY UPLC BEH C18 VanGuard pre-column (130 , 1.7 m, 2.1 mm5 mm) connected to a Waters XEVO G2-S quadrupole time-of-flight (QTOF) mass spectrometer equipped with an electrospray ionization (ESI) source operated in negative ionization mode. Compound separation was carried out using the gradient of the first LC-MS method. Gibberellin accumulation was detected by investigating extracted ion chromatograms (EICs) corresponding to their theoretical accurate mass.
TABLE-US-00005 TABLE 5 LC-MS analytical characterization. Typical retention Descrip- Molecular Monoisotopic m/z trace time (t.sub.R) tion formula mass (SIR) [min] GA.sub.3 C.sub.19H.sub.22O.sub.6 [M] 346.1416 344.98 0.5 1.02 [M H].sup. 345.1338 GA.sub.4 C.sub.19H.sub.24O.sub.5 [M] 332.1545 331.16 0.5 2.53 [M H].sup. 331.1545 GA.sub.7 C.sub.19H.sub.22O.sub.5 [M] 330.1467 329.15 0.5 2.47 [M H].sup. 329.1389
[0341] As shown in
[0342] As shown in
Example 3. Analysis of Bifunctional CDPS-KS Homologs
[0343] The expression of GGPPS producing genes alone has been shown to cause cell toxicity, therefore, GGPPS was removed by the expression of CDPS and KS genes. CDPS-KS bifunctional genes were constructed to determine the efficiency of each CDPS/KS combination for removing GGPPS by converting GGPPS to kaurenoic acid. CDPS-KS bifunctional fusion genes were comparatively tested in a yeast strain inserted with CytB5-1 and CytB5red-1. The strain was then transformed with CPR12 (SEQ ID NO:167 (nt) and SEQ ID NO:168 (aa)), RsKO_GA (SEQ ID NO:169 (nt) and SEQ ID NO:170 (aa)), GGPPS7 (SEQ ID NO:176 (aa) and SEQ ID NO:178 (aa)), KO1 (SEQ ID NO:171 (nt) and SEQ ID NO:172 (aa)), and either CDPS-KS6+KS5 (SEQ ID NO:101 (nt) and SEQ ID NO:102 (aa), and SEQ ID NO:181 (nt) and SEQ ID NO:182 (aa)), CDPS-KS6 (SEQ ID NO:101 (aa) and SEQ ID NO:102 (nt)), CDPS-KS4 (SEQ ID NO:226 (nt) and SEQ ID NO:227 (aa)), or CDPS-KS9 (SEQ ID NO:228 (nt) and SEQ ID NO:229 (aa)). The expression of the giberellin pathway genes along with CDPS-KS bifunctional genes were tested to determine the production level of kaurenoic acid. Greater levels of production of kaurenoic acid by a bifunctional CDPS-KS gene alone were produced by the expression of the CDPS-KS6 gene (115.14 M) and this was enhanced by the co-expression of KS5 (CDPS-KS6+KS5) (182.70 M). The bifunctional CDPS-K4 was less effective in the removal of GGPP as evidenced by the smaller amount of production of kaurenoic acid (8.80 M) when compared to bifunctional CDPS-KS6 (see Table 6).
TABLE-US-00006 TABLE 6 Conversion of GGPPS to Kaurenoic Acid by bifunctional CDPS-KS homologs. Kaurenoic Bi-Functional CDPS-KS gene Acid (M) Stddev CDPS-KS6 + KS5 182.70 17.8 CDPS-KS6 115.14 14.10024 CDPS-KS4 8.80 2.975735
Example 4. Analysis of KAO Homologs
[0344] The production level of gibberellins and gibberellin metabolites can vary depending on the expression of a KAO gene. To determine the amount of GA.sub.12 and GA.sub.14 produced by KAO activity, a yeast strain containing KO1 (SEQ ID NO:171 (nt) and SEQ ID NO:172 (aa)) and CPR19 (SEQ ID NO:193 (nt) and SEQ ID NO:194 (aa)) was transformed with CDPS-KS6 (SEQ ID NO:101), KS5 (SEQ ID NO:181), GGPPS7 (SEQ ID NO:177), KO1 (SEQ ID NO:171), KAO and CPR genes using USER based DNA assembler vectors and NatMx marker. Transformants were then grown and metabolites were analyzed using LC-MS. Yeast strains co-expressed KAO3/CPR19 genes (SEQ ID NO:230 and SEQ ID NO:193), KAO4/CPR17 (SEQ ID NO:73 and SEQ ID NO:187) or CPR19 (SEQ ID NO:193) genes, or KAO5/CPR12 (SEQ ID NO:61 and SEQ ID NO:167) or CPR19 genes (SEQ ID NO:193). The KAO3 and KAO5 genes used were obtained from Integrated DNA Technologies (IDT), and the KAO4 gene used was obtained from GeneArt (Invitrogen). Expression of KAO3 resulted in the production 1205 (AUC) of GA.sub.12 and 25055 (AUC) of GA.sub.14. Expression of KAO4 resulted in the production 4175 (AUC) GA.sub.12 and 127115 (AUC) GA.sub.14. Lastly, expression of KAO5 resulted in the production of 1605 (AUC) GA.sub.14.
TABLE-US-00007 TABLE 7 Production of GA.sub.12 and GA.sub.14 by KAO homologs. KAO homolog gene GA.sub.12 GA.sub.14 KAO3 (Fusarium fujikuroi) (IDT) 1205 25055 KAO4 (Spaceloma manihoticola) (GeneArt) 4175 127115 KAO5 (Ustilaginoidea virens) (IDT) 1605
[0345] Additional yeast studies were conducted to determine the production of gibberellins by various codon-optimized versions of KAO. KAO1 and KAO3 were both codon-optimized versions of F. fujikuroi while KAO2 and KAO4 were codon-optimized versions of F. proliferatum and S. manihoticola, respectively. A yeast train containing FfCytB5-1 (SEQ ID NO:159 (nt) and SEQ ID NO:160 (aa)), FfCytB5red-1 (SEQ ID NO:01 (nt) and SEQ ID NO:02 (aa)), CPR19 (SEQ ID NO:193 (nt) and SEQ ID NO:194 (aa)), RsKO-GA (SEQ ID NO:169 (nt) and SEQ ID NO:170 (aa)), KS5 (SEQ ID NO:181 (nt) and SEQ ID NO:182 (aa)), tCDPS5 (SEQ ID NO:179 (nt) and SEQ ID NO:180 (aa)), GGPPS7 (SEQ ID NO:177 (nt) and SEQ ID NO:178 (aa)), and KO1 (SEQ ID NO:171 (nt) and SEQ ID NO:172 (aa)) was transformed with P450-3-1 (SEQ ID NO:45), P450-2-4 (SEQ ID NO:141), P450-3-4 (SEQ ID NO:185), DES-1 (SEQ ID NO:25), and either KAO1 (SEQ ID NO:89), KAO3 (SEQ ID NO:145), KAO4 (SEQ ID NO:73) or KAO5 (SEQ ID NO:61). USER based DNA assembler vectors and URA3 markers were used. Transformants were then grown and metabolites were analyzed using LC-MS. Various amounts of metabolites from GA.sub.14 and further downstream the gibberellin pathway were produced (see Table 8). All numerical values in Tables 7 and 8 are area under curve (AUC).
TABLE-US-00008 TABLE 8 Production of Gibberellins and Gibberellin Metabolites by KAO homologs KAO homolog gene GA.sub.1 GA.sub.12 GA.sub.14 GA.sub.3 GA.sub.4 GA.sub.7 KAO1 1100 19150 15745 15645 5235 935 (F. fujikuroi) KAO2 3175 1615 1895 795 995 (F. proliferatum) KAO3 1290 16385 16635 14715 7050 870 (F. fujikuroi) KAO4 5065 30895 43295 24305 15065 2675 (S. manihoticola)
Example 5. Analysis of P450-2 Homologs
[0346] Gibberellin acid 14 (GA.sub.14) is converted to GA.sub.4 and GA.sub.1 by P450 enzymes. A comparative study of P450-2 homologs was conducted to determine the production level of gibberellins. A yeast strain inserted with P450-3-4 (SEQ ID NO:141 (nt) and SEQ ID NO:142 (aa)), KO1 (SEQ ID NO:170 (nt) and SEQ ID NO:171 (aa)), GGPPS7 (SEQ ID NO:177 (nt) and SEQ ID NO:178 (aa)), CDPS-KS6 (SEQ ID NO:101 (nt) and SEQ ID NO:102 (aa)), KAO4 (SEQ ID NO:73 (nt) and SEQ ID NO:74 (aa)), FfCytB5-1 (SEQ ID NO:159 (nt) and SEQ ID NO:160 (aa)), CPR1 (SEQ ID NO:165 (nt) and SEQ ID NO:166 (aa)), CPR19 (SEQ ID NO:193 (nt) and SEQ ID NO:194 (aa)), and various P450-2 genes. To identify which P450-2 gene was more efficient at the production of GA.sub.1, P450-2-1 (SEQ ID NO:79 (nt) and SEQ ID NO:80 (aa)), P450-2-8 (SEQ ID NO:232 (nt) and SEQ ID NO:233 (aa)), P450-2-9 (SEQ ID NO:234 (nt) and SEQ ID NO:235 (aa)), and P450-2-10 (SEQ ID NO:236 (nt) and SEQ ID NO:237 (aa)) were tested. The combination of genes resulted in the production of GA.sub.1. P450-2-1 produced greater levels of both GA.sub.1 (30309 AUC) and GA.sub.4 (34370 AUC) when compared to the other P450-2 enzymes tested, while P450-2-10 produced a smaller amount of GA.sub.1 (13611 AUC) and P450-2-8 produced a smaller amount of GA.sub.4 (17854 AUC) when compared to the other P450-2 enzymes tested (see Table 9).
TABLE-US-00009 TABLE 9 Productionof GA.sub.1 and GA.sub.4 by the expression of P450-2 homologs. P450-2 Homolog GA.sub.1 GA.sub.4 P450-2-1 F. fujikuroi 30309 34370 P450-2-8 F. fujikuroi 16472 17854 codon optimized (IDT) P450-2-9 F. Fujikuroi 18618 30038 P450-2-10 Phaeosphaeria sp. L487 13611 20440
[0347] P450-2 enzymes use GA.sub.14 as a substrate to produce GA.sub.4. To determine the production level of GA.sub.4 by P450-2 activity, P450-2 genes were introduced into a GA.sub.14 producing strain by integration into the yeast genome using a USER cloning based vector system. Each P450 gene was introduced using the URA3 selection marker. P450-2-1 and P450-2-6 (SEQ ID NO:17, SEQ ID NO:18) produced surprising levels of GA.sub.4 that were greater levels of GA.sub.4 (581,138 AUC and 279,002 AUC, respectively) when compared to the other P450-2 enzymes tested, while P450-2-4 produced a smaller amount of GA.sub.4 (3456.88 AUC) (see Table 10). All numerical values in Tables 9 and 10 are area under the curve (AUC).
TABLE-US-00010 TABLE 10 Production of GA.sub.4 by the expression of P450-2 genes. P450-2 Homolog GA.sub.4 Fusarium fujikuroi P450-2-1 581,138 Fusarium fujikuroi P450-2-4 3,457 Ustilaginoidea virens P450-2-5 24,058 Fusarium oxysporum P450-2-6 279,002
Example 6. Activity of KAO Genes in GA.SUB.12.-Producing S. Cerevisiae Strains
[0348] Using the USER cloning based yeast integration system, the genes in Table 11 were individually introduced into an S. cerevisiae strain that further comprised a gene encoding a G. fujikuroi CPR5 polypeptide (SEQ ID NO:47 (nt), SEQ ID NO:48 (aa)), a gene encoding a CPR12 polypeptide (SEQ ID NO:167 (nt), SEQ ID NO:168 (aa)), a gene encoding an A. thaliana KS5 polypeptide (SEQ ID NO:181 (nt), SEQ ID NO:182 (aa)), a gene encoding a truncated Zea mays CDPS polypeptide (SEQ ID NO:179 (nt), SEQ ID NO:180 (aa)), a gene encoding an ERG20-GGPPS7 polypeptide (SEQ ID NO:220 (nt), SEQ ID NO:221 (aa)), and a gene encoding a Stevia rebaudiana KO1 polypeptide (SEQ ID NO:171 (nt), SEQ ID NO:172 (aa)). See the pathway described in
TABLE-US-00011 TABLE 11 KAO genes tested for production of gibberellins. KAO SEQ ID NO A. thaliana KAO5 SEQ ID NO: 61 (nt) SEQ ID NO: 62 (aa) A. thaliana KAO6 SEQ ID NO: 59 (nt) SEQ ID NO: 60 (aa) H. vulgare KAO9 SEQ ID NO: 67 (nt) SEQ ID NO: 68 (aa) P. sativum KAO10 SEQ ID NO: 57 (nt) SEQ ID NO: 58 (aa) P. sativum KAO11 SEQ ID NO: 63 (nt) SEQ ID NO: 64 (aa) S. manihoticola KAO4 SEQ ID NO: 73 (nt) SEQ ID NO: 74 (aa)
[0349] Co-expression of C. maxima GA.sub.20ox-4 (SEQ ID NO:39 (nt), SEQ ID NO:40 (aa)), Oryza sativa GA.sub.13ox (SEQ ID NO:97, SEQ ID NO:98), P. sativum KAO11 (SEQ ID NO:63 (nt), SEQ ID NO:64 (aa)), and C. maxima Ga.sub.7ox-1 (SEQ ID NO:151 (nt), SEQ ID NO:152 (aa)) in the kaurenoic acid-producing S. cerevisiae strain further resulted in accumulation of GA.sub.9 and GA.sub.20. See the pathway described in
Example 7. Activity of CYP117, CYP114, and CYP112 in GA.SUB.4.- and GA.SUB.9.-Producing S. Cerevisiae Strains
[0350] Using the USER cloning based yeast integration system, the genes in Table 12 or Table 13 were introduced into an S. cerevisiae strain that further comprised a gene encoding a G. fujikuroi CPR5 polypeptide (SEQ ID NO:47 (nt), SEQ ID NO:48 (aa)), a gene encoding a CPR12 polypeptide (SEQ ID NO:167 (nt), SEQ ID NO:168 (aa)), a gene encoding an A. thaliana KS5 polypeptide (SEQ ID NO:181 (nt), SEQ ID NO:182 (aa)), a gene encoding a truncated Z. mays CDPS polypeptide (SEQ ID NO:179 (nt), SEQ ID NO:180 (aa)), a gene encoding an ERG20-GGPPS7 polypeptide (SEQ ID NO:220 (nt), SEQ ID NO:221 (aa)), and a gene encoding a Stevia rebaudiana KO1 polypeptide (SEQ ID NO:171 (nt), SEQ ID NO:172 (aa)). See the pathways described in
TABLE-US-00012 TABLE 12 Genes expressed in S. cerevisiae strain P. Gene 1 SEQ Gene 2 SEQ Gene 1 ID NOs Gene 2 ID NOs P. sativum SEQ ID NO: C. maxima SEQ ID NO: KAO11 63 (nt) GA.sub.7ox 151 (nt) SEQ ID NO: SEQ ID NO: 64 (aa) 152 (aa) B. diazoefficiens SEQ ID NO: B. diazoefficiens SEQ ID NO: ADH 115 (nt) CYP112 123 (nt) SEQ ID NO: SEQ ID NO: 116 (aa) 124 (aa) P. putida SEQ ID NO: P. putida SEQ ID NO: ferredoxin 147 (nt) ferredoxin 149 (nt) SEQ ID NO: reductase SEQ ID NO: 148 (aa) 150 (aa)
TABLE-US-00013 TABLE 13 Genes expressed in S. cerevisiae strain U. Gene 1 SEQ Gene 2 SEQ Gene 1 ID NOs Gene 2 ID NOs S. manihoticola SEQ ID NO: KO SEQ ID NO: KAO4 73 (nt) 169 (nt) SEQ ID NO: SEQ ID NO: 74 (aa) 170 (aa) B. diazoefficiens SEQ ID NO: B. diazoefficiens SEQ ID NO: ADH 115 (nt) CYP112 123 (nt) SEQ ID NO: SEQ ID NO: 116 (aa) 124 (aa) P. putida SEQ ID NO: P. putida SEQ ID NO: ferredoxin 147 (nt) ferredoxin 149 (nt) SEQ ID NO: reductase SEQ ID NO: 148 (aa) 150 (aa)
Example 8. Expression of P450-1 Genes for Production of GA.SUB.14
[0351] An S. cerevisiae strain comprising a gene encoding a P450-1 polypeptide (SEQ ID NO:87 (nt), SEQ ID NO:88 (aa)) or a P450-1 polypeptide (SEQ ID NO:145 (nt), SEQ ID NO:146 (aa)), a KAO4 polypeptide (SEQ ID NO:73 (nt), SEQ ID NO:74 (aa)), or a KAO1 polypeptide (SEQ ID NO:89 (nt), SEQ ID NO:90 (aa)) was engineered to accumulate kaurenoic acid, as described in Example 2. Using the USER based yeast integration vector system, S. manihoticola KAO4 polypeptide (SEQ ID NO:73 (nt), SEQ ID NO:74 (aa)) or G. fujikuroi KAO1 polypeptide (SEQ ID NO:89 (nt), SEQ ID NO:90 (aa)) individually introduced into the S. cerevisiae strain. As shown in
Example 9. Engineering of S. Cerevisiae Strain Comprising Cytochrome B5 and Cytochrome B5 Reductase with CPR14, CPR15, or CPR16
[0352] Using the USER based yeast integration vector system, the genes in Table 14, Table 15, or Table 16 were introduced into an S. cerevisiae strain that further comprised a gene encoding a truncated CDPS polypeptide (SEQ ID NO:179 (nt), SEQ ID NO:180 (aa)), a KS polypeptide (SEQ ID NO:181 (nt), SEQ ID NO:182 (aa)), a KO polypeptide (SEQ ID NO:171 (nt), SEQ ID NO:172 (aa)), a CPR polypeptide (SEQ ID NO:167 (nt), SEQ ID NO:168 (aa)), and an ERG20-GGPPS7 polypeptide (SEQ ID NO:195 (nt), SEQ ID NO:196 (aa)). The strains described in Tables 14-16 were identical, except that they comprised either CPR14, CPR15, or CPR16.
TABLE-US-00014 TABLE 14 Genes expressed in S. cerevisiae strain CPR16. Gene 1 SEQ Gene 2 SEQ Gene 1 ID NOs Gene 2 ID NOs G. fujikuroi SEQ ID NO: G. fujikuroi SEQ ID NO: P450-2-1 79 (nt) P450-3-4 185 (nt) SEQ ID NO: SEQ ID NO: 80 (aa) 186 (aa) A. niger SEQ ID NO: G. fujikuroi SEQ ID NO: CPR16 157 (nt) DES-1 25 (nt) SEQ ID NO: SEQ ID NO: 158 (aa) 26 (aa) G. fujikuroi SEQ ID NO: G. fujikuroi SEQ ID NO: Cytochrome B5 159 (nt) Cytochrome B5 01 (nt) SEQ ID NO: reductase SEQ ID NO: 160 (aa) 02 (aa)
TABLE-US-00015 TABLE 15 Genes expressed in S. cerevisiae strain CPR14. Gene 1 SEQ Gene 2 SEQ Gene 1 ID NOs Gene 2 ID NOs G. fujikuroi SEQ ID NO: G. fujikuroi SEQ ID NO: P450-2-1 79 (nt) P450-3-4 185 (nt) SEQ ID NO: SEQ ID NO: 80 (aa) 186 (aa) Phaeosphaeria sp. SEQ ID NO: G. fujikuroi SEQ ID NO: CPR14 99 (nt) DES-1 25 (nt) SEQ ID NO: SEQ ID NO: 100 (aa) 26 (aa) G. fujikuroi SEQ ID NO: G. fujikuroi SEQ ID NO: Cytochrome B5 159 (nt) Cytochrome B5 01 (nt) SEQ ID NO: reductase SEQ ID NO: 160 (aa) 02 (aa)
TABLE-US-00016 TABLE 16 Genes expressed in S. cerevisiae strain CPR15. Gene 1 SEQ Gene 2 SEQ Gene 1 ID NOs Gene 2 ID NOs G. fujikuroi SEQ ID NO: G. fujikuroi SEQ ID NO: P450-2-1 79 (nt) P450-3-4 185 (nt) SEQ ID NO: SEQ ID NO: 80 (aa) 186 (aa) Candida SEQ ID NO: G. fujikuroi SEQ ID NO: apicola 139 (nt) DES-1 25 (nt) CPR15 SEQ ID NO: SEQ ID NO: 140 (aa) 26 (aa) G. fujikuroi SEQ ID NO: G. fujikuroi SEQ ID NO: Cytochrome 159 (nt) Cytochrome 01 (nt) B5 SEQ ID NO: B5 reductase SEQ ID NO: 160 (aa) 02 (aa)
[0353] As shown in
Example 10. Engineering of S. Cerevisiae Strain for Production of Gibberellin A4 (GA.SUB.4.)
[0354] Using the USER based yeast integration vector system, the genes in Table 17 were stably integrated into an S. cerevisiae strain. The strain was grown in a 2 L Sartorius fermentor using a fed batch process. Temperature, pH, agitation, and aeration rate were controlled throughout the cultivation. The temperature was maintained at 30 C. Air was used for sparging the bioreactor at 1 vvm (L gas/(L liquidmin)). pH was controlled at pH 5.0 by automatic addition of NH.sub.4OH. An 8% NH.sub.4OH solution was used for the first 45 hours of the process; a 16% solution was used for the final part. The stirrer speed was initially set to 800 rpm and increased to up to 1600 rpm during the process. The basis for the medium used for the batch phase is 0.5 L minimal medium containing glucose, salts, vitamins and trace metals. The feed solution was either a high density glucose solution with salts, trace metals and vitamins (glucose feed) or 96% ethanol (ethanol feed). Antifoam was included in the batch medium and feed medium. The fermentation was inoculated using a seed train in shake flasks grown at 30 C. using a minimal medium with similar content as the medium used for the batch phase in the fermentation. The batch fermentation lasted for 16 hours. During the carbon-limited fed batch phase, feed was added following an exponential feed profile feeding with glucose feed from 16-70 hours and ethanol feed from 70-160 hours. Since the ethanol feed only contained the carbon source, concentrated feed components (salts, vitamins, trace metals and antifoam) were combined, sterile filtered and added to the fermentation broth once or twice per day during feeding with ethanol feed.
TABLE-US-00017 TABLE 17 Genes integrated in S. cerevisiae strain for production of gibberellin A4 (GA.sub.4). Gene SEQ ID NOs DAP1-2 SEQ ID NO: 212 (nt) F. fujikuroi SEQ ID NO: 213 (aa) ICE2-2 SEQ ID NO: 205 (nt) F. fujikuroi SEQ ID NO: 206 (aa) CDPS-K56 SEQ ID NO: 101 (nt) F. fujikuroi SEQ ID NO: 102 (aa) KS5 SEQ ID NO: 181 (nt) A. thaliana SEQ ID NO: 182 (aa) FfCytB5-1 SEQ ID NO: 159 (nt) (codon optimized) SEQ ID NO: 160 (aa) F. fujikuroi KAO3 SEQ ID NO: 145 (nt) G. fujikuroi SEQ ID NO: 146 (aa) CPR19 SEQ ID NO: 193 (nt) G. fujikuroi SEQ ID NO: 194 (aa) CPR12 SEQ ID NO: 167 (nt) R. suavissimus SEQ ID NO: 168 (aa) RsKO SEQ ID NO: 169 (nt) R. suavissimus SEQ ID NO: 170 (aa) GGPPS-7 SEQ ID NO: 177 (nt) Synecococcus sp. SEQ ID NO: 178 (aa) KO1 SEQ ID NO: 171 (nt) S. rebaudiana SEQ ID NO: 172 (aa) P450-2-1 SEQ ID NO: 79 (nt) G. fujikuroi SEQ ID NO: 80 (aa)
[0355] As shown in
TABLE-US-00018 TABLE 18 Production of additional gibberellins and intermediates. Time point GA.sub.4 GA.sub.14 KA (hrs) (M) (M) (M) 0 0 0 0 47 642 44 15 71 1313 54 79 95 2600 120 1308 100 2800 118 1754 119 4659 96 3090 125 4900 88 4666 143 5462 80 6138 149 5845 73 6898 167 6644 88 7608
Example 11. Production of GA.SUB.3 .Using Fungal Gibberellin Pathway Genes
[0356] Using the USER based yeast integration vector system, the genes in Table 19 were stably integrated into an S. cerevisiae strain. The strain was grown in a 2 L Sartorius fermentor using a fed batch process. Temperature, pH, agitation, and aeration rate were controlled throughout the cultivation. The temperature was maintained at 30 C. Air was used for sparging the bioreactor at 1 vvm (L gas/(L liquidmin)). pH was controlled at pH 5.0 by automatic addition of NH.sub.4OH. An 8% NH.sub.4OH solution was used for the first 45 hours of the process; a 16% solution was used for the final part. The stirrer speed was initially set to 800 rpm and increased to up to 1600 rpm during the process. The basis for the medium used for the batch phase is 0.5 L minimal medium containing glucose, salts, vitamins and trace metals. The feed solution was either a high density glucose solution with salts, trace metals and vitamins (glucose feed) or 96% ethanol (ethanol feed). Antifoam was included in the batch medium and feed medium. The fermentation was inoculated using a seed train in shake flasks grown at 30 C. using a minimal medium with similar content as the medium used for the batch phase in the fermentation. The batch fermentation lasted for 16 hours. During the carbon-limited fed batch phase, feed was added following an exponential feed profile feeding with glucose feed from 16-70 hours and ethanol feed from 70-148 hours. Since the ethanol feed only contained the carbon source, concentrated feed components (salts, vitamins, trace metals and antifoam) were combined, sterile filtered and added to the fermentation broth once or twice per day during feeding with ethanol feed. After 148 hours of fermentation, the titer in growth medium was measured to be 491 mg/L (1.42 mM) of GA.sub.3 and 2.15 mM of kaurenol, 4.26 mM of kaurenal and 1.28 mM ent-kaurene. The production of GA.sub.3, GA.sub.4 and additional gibberellins and intermediate molecules at various time points during growth in the culture medium is shown in Table 20. The results demonstrate that a yeast strain comprising fungal gibberellin genes can produce gibberellins.
TABLE-US-00019 TABLE 19 Genes integrated in S. cerevisiae strain for production of gibberellins, including GA.sub.3 Gene SEQ ID NOs DAP1-2 SEQ ID NO: 212 (nt) F. fujikuroi SEQ ID NO: 213 (aa) ICE2-2 SEQ ID NO: 205 (nt) F. fujikuroi SEQ ID NO: 206 (aa) CDPS-KS-6 SEQ ID NO: 101 (nt) F. fujikuroi SEQ ID NO: 102 (aa) KS5 SEQ ID NO: 181 (nt) A. thaliana SEQ ID NO: 182 (aa) FfCytB5-1 SEQ ID NO: 159 (nt) (codon optimized) SEQ ID NO: 160 (aa) F. fujikuroi FfCytB5red-1 SEQ ID NO: 01 (nt) (codon optimized) SEQ ID NO: 02 (aa) F. fujikuroi KAO3 SEQ ID NO: 145 (nt) G. fujikuroi SEQ ID NO: 146 (aa) CPR19 SEQ ID NO: 193 (nt) G. fujikuroi SEQ ID NO: 194 (aa) CPR12 SEQ ID NO: 167 (nt) R. suavissimus SEQ ID NO: 168 (aa) RsKO SEQ ID NO: 169 (nt) R. suavissimus SEQ ID NO: 170 (aa) GGPPS-7 SEQ ID NO: 177 (nt) Synecococcus sp. SEQ ID NO: 178 (aa) KO1 SEQ ID NO: 171 (nt) S. rebaudiana SEQ ID NO: 172 (aa) P450-2-1 SEQ ID NO: 79 (nt) G. fujikuroi SEQ ID NO: 80 (aa) KAO4 SEQ ID NO: 73 (nt) S. manihoticola SEQ ID NO: 74 (aa) DES-1 SEQ ID NO: 25 (nt) F. fujikuroi SEQ ID NO: 26 (aa)
TABLE-US-00020 TABLE 20 Gibberellin production in samples. GA.sub.1 GA.sub.3 GA.sub.4 GA.sub.13 GA.sub.14 GA.sub.25 KA Hours (mM) (mM) (mM) (mM) (mM) (mM) (mM) 0 0 0 0 0 0 0 0 46 0 0.261 0.0219 0.025 0.0504 0.00166 0.1723 71 0.0475 0.7185 0.0479 0.087 0.111 0.0482 1.472 94 0.2074 0.8399 0.1604 0.119 0.2169 0.114 1.486 118 0.4897 1.1385 0.1726 0.187 0.3098 0.187 2.836 124 0.5221 1.3315 0.1693 0.215 0.3197 0.203 2.825 142 0.547 1.3452 0.1438 0.224 0.1983 0.187 2.6623 148 0.681 1.4241 0.1684 0.257 0.1985 0.209 3.833
Example 12. Engineering of S. Cerevisiae Strain for Production of Gibberellin .SUB.3 .(GA.SUB.3.) Comprising Plant GA.SUB.3ox .Genes
[0357] Using the USER based yeast integration vector system, the genes in Table 19 were stably integrated into an S. cerevisiae strain. The strain was grown in DELFT culture medium supplemented with uracil to complement uracil auxotrophy of the strain for 96 hours. Samples were extracted with acetonitrile (80% final) and cultures were analysed using LC-MS. The production of GA.sub.4 and additional gibberellins and intermediate molecules at various time points during growth in the culture medium is shown in Table 22.
TABLE-US-00021 TABLE 21 Genes integrated in S. cerevisiae strain for production of Gibberellins, including GA.sub.3. Gene SEQ ID NOs DAP1-2 SEQ ID NO: 212 (nt) F. fujikuroi SEQ ID NO: 213 (aa) CytB5-2 SEQ ID NO: 238 (nt) SEQ ID NO: 239 (aa) CytB5red-4 SEQ ID NO: 240 (nt) SEQ ID NO: 241 (aa) FfCytB5-1 SEQ ID NO: 159 (nt) (codon optimized) SEQ ID NO: 160 (aa) F. fujikuroi FfCytB5red-1 SEQ ID NO: 01 (nt) (codon optimized) SEQ ID NO: 02 (aa) F. fujikuroi KAO11 SEQ ID NO: 63 (nt) P. sativum SEQ ID NO: 64 (aa) CPR12 SEQ ID NO: 167 (nt) R. suavissimus SEQ ID NO: 168 (aa) CDPS-K56 SEQ ID NO: 101 (nt) F. fujikuroi SEQ ID NO: 102 (aa) KS5 SEQ ID NO: 181 (nt) A. thaliana SEQ ID NO: 182 (aa) GGPPS-7 SEQ ID NO: 177 (nt) Synecococcus sp. SEQ ID NO: 178 (aa) KO1 SEQ ID NO: 171 (nt) S. rebaudiana SEQ ID NO: 172 (aa) GA13ox-1 SEQ ID NO: 97 (nt) O. sativa SEQ ID NO: 98 (aa) GA20ox-4 SEQ ID NO: 39 (nt) C. maxima SEQ ID NO: 40 (aa) GA3ox-1 SEQ ID NO: 27 (nt) M. macrocarpus SEQ ID NO: 28 (aa)
TABLE-US-00022 TABLE 22 Gibberellin production in samples. Sample GA.sub.4 Kaurenoic Name Genes added to strain GA.sub.12 GA.sub.20 GA.sub.4 (M) GA.sub.53 GA.sub.9 acid (M) A8 GA13-1 + GA20-4 + 131195 12295 1.7 2650 9515 142 GA3-1 + CPR12 B1 GA13-1 + GA20-4 + 49045 1655 20950 2.8 56745 267 GA3-1 C5 GA13-1 + GA20-4 + 52565 12895 1000 0.4 25460 48505 248 GA3-2 + CPR12 D12 GA13-1 + GA20-4 + 37435 8295 1810 0.5 36520 39465 222 GA3-2 E11 GA13-1 + GA20-4 + 44830 9910 0.0 21450 46010 214 GA3-3 + CPR12 F7 GA13-1 + GA20-4 + 33515 14010 0.0 26235 33335 220 GA3-3 G4 GA13-1 + GA20-4 + 28910 8860 26495 3.6 7845 25180 108 GA3-4 + CPR12 H9 GA13-1 + GA20-4 + 34550 9990 16545 2.2 31830 4160 144 GA3-4 Values are AUC values, except for GA(uM) and Kaurenoic acid (uM)
[0358] These results demonstrated that plant GA13 ox, GA20 ox and GA3 ox genes were all active in yeast and that when combined they can catalyse the reactions from GA.sub.12 to GA.sub.53 (GA13 ox reaction) to GA.sub.9 (GA20 ox reaction) to GA.sub.20 (GA13 ox+GA20 ox reactions via either GA.sub.53 or GA.sub.9) and then further GA.sub.9 to GA.sub.4 reaction catalyzed by GA.sub.3ox genes. Further analysis revealed that sample B1 and sample C5 also contained small amounts of GA.sub.3, which thereby demonstrated a fully functional GA.sub.3 pathway from ent-kaurene based on plant derived genes (see
Example 13. Production of Gibberellin .SUB.3 .(GA.SUB.3.) and Other Gibberellins Using a S. Cerevisiae Strain Comprising Plant GA20 Oxidase, GA3 Oxidase and GA13 Oxidase Genes
[0359] The B1 strain from Example 12 was grown in a 2 L Sartorius fermentor using a fed batch process. Temperature, pH, agitation, and aeration rate were controlled throughout the cultivation. The temperature was maintained at 30 C. Air was used for sparging the bioreactor at 1 vvm (L gas/(L liquidmin)). pH was controlled at pH 5.0 by automatic addition of NH.sub.4OH. An 8% NH.sub.4OH solution was used for the first 45 hours of the process; a 16% solution was used for the final part. The stirrer speed was initially set to 800 rpm and increased to up to 1600 rpm during the process. The basis for the medium used for the batch phase is 0.5 L minimal medium containing glucose, salts, vitamins and trace metals. The feed solution was either a high density glucose solution with salts, trace metals and vitamins (glucose feed) or 96% ethanol (ethanol feed) supplemented with uracil to complement uracil auxotrophy of the strain. Antifoam was included in the batch medium and feed medium. The fermentation was inoculated using a seed train in shake flasks grown at 30 C. using a minimal medium with similar content as the medium used for the batch phase in the fermentation. The batch fermentation lasted for 16 hours. During the carbon-limited fed batch phase, feed was added following an exponential feed profile feeding with glucose feed from 16-70 hours and ethanol feed from 70-138 hours. Since the ethanol feed only contained the carbon source, concentrated feed components (salts, vitamins, trace metals and antifoam) were combined, sterile filtered and added to the fermentation broth once or twice per day during feeding with ethanol feed.
[0360] As shown in Table 23, the strain accumulated gibberellins, including, but not limited to GA.sub.3, GA.sub.4 and GA.sub.14. After approximately 138 hours of fermentation, the titer in growth medium was 1.7 M of GA.sub.3, 73 M of GA.sub.1, 82 M of GA.sub.4, 1.8 M GA.sub.7, 2400 M of KA as well as estimated amounts of 214 M of GA.sub.20, 1.5 M of GA.sub.9, 134 M of GA.sub.24, 128 M of GA.sub.53 and 142 M of GA.sub.12. The production of additional gibberellins and intermediate molecules at various time points during growth in the culture medium is shown in Table 23.
TABLE-US-00023 TABLE 23 Production of additional gibberellins and intermediates. Time point GA.sub.3 GA.sub.1 GA.sub.7 GA.sub.4 KA GA.sub.20 GA.sub.9 GA.sub.24 GA.sub.53 GA.sub.12 (hrs) (M) (M) (M) (M) (M) (M) (M) (M) (M) (M) 116 h 1.4 47 0 48 388 4.7 2.5 32 38 39 138 h 1.7 73 1.8 482 2400 214 1.5 134 128 142
Example 14. Engineering of S. Cerevisiae Strain for Production of Gibberellin A.SUB.3 .(GA.SUB.3.) Comprising Plant GA.SUB.13ox .Genes
[0361] Using the USER based yeast integration vector system, the genes in Table 24 and Table 25 were stably integrated into an S. cerevisiae strain comprising the genes as shown in Table 17. The strain was grown in DELFT culture medium for 96 hours. Samples were extracted with acetonitrile (80% final) and cultures were analyzed using LC-MS. By testing plant GA.sub.13 oxidase in a GA.sub.4 producing strain, the results demonstrate that the plant GA.sub.13 oxidase can replace the fungal P450-3 enzyme, which is demonstrated by the formation of GA.sub.1 and GA.sub.3. See Table 26.
TABLE-US-00024 TABLE 24 Genes integrated in S. cerevisiae strain for production of Gibberellins (Transformants H1, H2 and H3) Gene SEQ ID No. GA13.sub.ox-1 SEQ ID NO: 97 (nt) Oryza sativa SEQ ID NO: 98 (aa) DES-1 SEQ ID NO: 25 (nt) Fusarium fujikuroi SEQ ID NO: 26 (aa)
TABLE-US-00025 TABLE 25 Genes integrated in S. cerevisiae strain for production of Gibberellins (Transformants I1, I2 and I3) Gene SEQ ID No. P450-3-4 SEQ ID NO: 185 (nt) Fusarium fujikuroi SEQ ID NO: 186 (aa) DES-1 SEQ ID NO: 25 (nt) Fusarium fujikuroi SEQ ID NO: 26 (aa)
TABLE-US-00026 TABLE 26 Production of additional gibberellins and intermediates. Unit: AUC M M AUC Epoxide AUC GA1 AUC AUC AUC AUC GA3 AUC AUC AUC AUC Kaurenoic Sample GA3 GA1 (M) GA12 GA13 GA14 GA3 (M) GA4 GA53 GA7 GA9 acid H1 37360 13 30740 67050 205185 3180 0.40 144395 29615 235460 6705 895 H2 58995 20 19280 71720 106075 1955 0.10 248700 43880 205265 8160 H3 60405 21 22755 52950 82190 800 0.04 345500 42085 91190 6575 I1 10760 85885 30 45290 85105 103710 87870 22.10 114315 0 6495 9955 I2 8265 62160 21 28320 79895 73755 63840 15.90 145540 0 7630 8395 I3 11700 91795 32 56205 92035 111315 90000 22.70 119980 0 6840 11305
[0362] Having described the invention in detail and by reference to specific embodiments thereof, it will be apparent that modifications and variations are possible without departing from the scope of the invention defined in the appended claims. More specifically, although some aspects of the present invention are identified herein as particularly advantageous, it is contemplated that the present invention is not necessarily limited to these particular aspects of the invention.
TABLE-US-00027 TABLE27 Sequencesdisclosedherein. SEQIDNO:1 atgtcctctaacggtgataaccattctttgttcgccagacattacatcgattatgtttat 60 gctccaggtttgttgttggttgtcggtactttgatcgttaagaaagaatgggctccatgg 120 gctttgttagttgctgttgtttttggtatctacaacttcatggccttccaagttaagact 180 actttgaagccagatgttttccaagaatttgaattggaagaaaagaccatcgtcagtcat 240 aacgttgctatctacagattcaaattgccatccccaaaacacattttgggtttgccaatt 300 ggtcaacacatttctattggtgctccatgtccacaaccagatggtactacaaaagaaatc 360 gttagatcctacaccccaatctctggtgatcatcaaccaggtcatgttgatttgttgatc 420 aagtcttacccacaaggtaacatctccaaacatatggcatctttgactgttggtcaaacc 480 attaaggttagaggtccaaaaggtgcttttgtctacactccaaatatggttagacacttc 540 ggtatgattgctggtggtactggtattactccaatgttgcaagttattagagccatcgtt 600 agaggtagagctgctggtgataagactgaagttgatttgattttcgctaacgttaccgcc 660 caagacatcttgttgaaagaagatttggacgctttggccaagcaagattctggtattaga 720 gttcattacgtcttggacaaacctgaagaaggttggactggtggtgttggttatgttact 780 gctgatatgatcgataagtacttgccaaaaccagccgatgatgttaagattttgttgtgt 840 ggtccaccaccaatgatttctggtttgaaaaaagctaccgaatccttgggttttaagaag 900 gctagaccagtttctaagttggttgaccaagttttcgctttttaa 945 SEQIDNO:2 MSSNGDNHSLFARHYIDYVYAPGLLLVVGTLIVKKEWAPWALLVAVVFGIYNFMAFQVKT 60 TLKPDVFQEFELEEKTIVSHNVAIYRFKLPSPKHILGLPIGQHISIGAPCPQPDGTTKEI 120 VRSYTPISGDHQPGHVDLLIKSYPQGNISKHMASLTVGQTIKVRGPKGAFVYTPNMVRHF 180 GMIAGGTGITPMLQVIRAIVRGRAAGDKTEVDLIFANVTAQDILLKEDLDALAKQDSGIR 240 VHYVLDKPEEGWTGGVGYVTADMIDKYLPKPADDVKILLCGPPPMISGLKKATESLGFKK 300 ARPVSKLVDQVFAF 314 SEQIDNO:3 atgtcagggcaatctctgccaacactacctatgtggcgtgttgatcatatagaaccgagt 60 cccgaaatgttggcactgagggctaatggtccaatccatagggtaaggtttccgtctggg 120 cacgagggttggtgggtgacaggttacgaagaggccaaggcagtgttgagcgacgccgct 180 tttagaccatccggtatgccgccagcagcattcacacccgcaacagtcatacttggttcc 240 ccaggttggttgggaagtcatgaaggttctgaacatgcaagattgagaacaattgtagct 300 cccgcattttcaaatagacgtgtgaagctactagcacaacagatcgaagcaattgctgca 360 caattgtttgaaacgctagcagcacaacctcagcccgctgatctgagacattacttatcc 420 tttcctcttcctgctatggtgattagtgccttgatgggtgtaccatatgaagatcacgct 480 ttttttgcagaacttagtgacgaagttatgacccaccaacatgagtccggtcctagaagc 540 gctgcgctactggcatggggagagttaaggacctacatcagaggcaaaatgagggggaaa 600 agacaagacccaggagataatctacttactgacttacttgctgccgttgatcagggcaag 660 gcaactgaggaagaagccataggtcttgctgcaggaattcttgttgcaggccacgaatca 720 actgttgcacaaatagaatttggtttactggctatgtccagacaccctcatcagcgtgag 780 agattagttggagatccatctttagtcgacaaggcagtggaggaaattttacgtatgtac 840 cctccaggcgccggatgggatggtattatgagatatcctagaactgatgtgacaatagcg 900 ggggttcatattccagctgaaagcaaagtgttagttggcttgcctgccacaagttttgat 960 ccccatcacttcgacgatcctgagaactttgatataggaagagcagaaaagcctcactta 1020 gctttttcatatggtcctcattattgcattggtgaagccttggcacgtttagaacttaag 1080 gtagtctttggttccatctttcaaagattcccgacgttgcgtttggctgtcgcacccgaa 1140 gagttaaagttaagaaaggatataatcacaggaggattcgaagaattccccgtattatgg 1200 taa 1203 SEQIDNO:4 MSGQSLPTLPMWRVDHIEPSPEMLALRANGPIHRVRFPSGHEGWWVTGYEEAKAVLSDAA 60 FRPSGMPPAAFTPATVILGSPGWLGSHEGSEHARLRTIVAPAFSNRRVKLLAQQIEAIAA 120 QLFETLAAQPQPADLRHYLSFPLPAMVISALMGVPYEDHAFFAELSDEVMTHQHESGPRS 180 AALLAWGELRTYIRGKMRGKRQDPGDNLLTDLLAAVDQGKATEEEAIGLAAGILVAGHES 240 TVAQIEFGLLAMSRHPHQRERLVGDPSLVDKAVEEILRMYPPGAGWDGIMRYPRTDVTIA 300 GVHIPAESKVLVGLPATSFDPHHFDDPENFDIGRAEKPHLAFSYGPHYCIGEALARLELK 360 VVFGSIFQRFPTLRLAVAPEELKLRKDIITGGFEEFPVLW 400 SEQIDNO:5 atgttcgaacagcctttgccgaccttgccgatgtggagagttgatcacatcgaaccttct 60 cctgagatgttagctctaagggctaaaggtccaatccatagagtgcgttttccttcaggg 120 catgagggatggtgggttactggttacgacgaagctcaagcagttttatcagatgctgcc 180 tttagaccagccggtatgcctccagaaacatttacaccggattcagttattttgggtagt 240 ccaggttggcttgtatctcacgaaggaggtaaacacgcttggctaagaatgattgttgcc 300 ccagcattctcaaataggagggtgaaattgttagcccaacaagtcgaggccatagctgct 360 caattgttcgaaacactggctgctcaaccacaaccagccgatttaagaagacacttatca 420 tttccattgccagctatggtgatttcagcactaatgggcgttttatatgaagatcatata 480 ttcttcgccggtttatcagacgaagtcatgacccaccaacatgagtccggcccgagatct 540 gccagcagagtcgcttgggaagagcttagaacctacatttgcagaaagatgagaggtaag 600 agggaagagccaggtgacaatttacttaccgatttgttggcggctgtggatcatggcaaa 660 gcaactgaagaagaggcagttggtttggctgccggtgttcttgtagcaggccatgaaagt 720 actgtagctcaaattgaatttggcctgttagctatgttcaggcacccccaacaaagggag 780 agattggttagagacccattcctagccgataaagctgtagaggaaattttaagaatgtac 840 agccccggcgctggttgggatggcattatgagataccctagaactgatgtcactatagct 900 ggtatggacattcccgccgaatcaaaagtcttagtgggtttacctgccacttcattcgac 960 ccaaggcacttcgaagatccggaagtatttgatataggtagggatccaaacccacaccta 1020 gcgttttcctatggcccacacaattgcatcggtgcagcattggctagacttgaattaaaa 1080 gtggtatttggttccatattccagagattcccggccctaaggctagctgtagctccagaa 1140 gaactgaagttgagaaaagaaataattacgggcgggtttgaagaatttccagtcctatgg 1200 SEQIDNO:6 MFEQPLPTLPMWRVDHIEPSPEMLALRAKGPIHRVRFPSGHEGWWVTGYDEAQAVLSDAA 60 FRPAGMPPETFTPDSVILGSPGWLVSHEGGKHAWLRMIVAPAFSNRRVKLLAQQVEAIAA 120 QLFETLAAQPQPADLRRHLSFPLPAMVISALMGVLYEDHIFFAGLSDEVMTHQHESGPRS 180 ASRVAWEELRTYICRKMRGKREEPGDNLLTDLLAAVDHGKATEEEAVGLAAGVLVAGHES 240 TVAQIEFGLLAMFRHPQQRERLVRDPFLADKAVEEILRMYSPGAGWDGIMRYPRTDVTIA 300 GMDIPAESKVLVGLPATSFDPRHFEDPEVFDIGRDPNPHLAFSYGPHNCIGAALARLELK 360 VVFGSIFQRFPALRLAVAPEELKLRKEIITGGFEEFPVLW 400 SEQIDNO:7 atgtctgaacaaccactaccgacccttccaatgtggagagtagaccacattgaaccgagt 60 cccgaaatgttggcccttagagctaatggacccatccatagagtgagattcccatccgga 120 cacgaaggctggtgggtcactggatatgatgaagccaaggctgtcttaagtgatactgcg 180 ttcagaccagccggaatgccaccagctgcttttactccggatagcgttatccttggcagt 240 ccgggttggttagtttcacacgaaggaggtgagcatacaagattaaggaccatagtcgcc 300 cctgcgtttggtgattcaagaatcaaattgTTagcacagcaagtcgaggccattgcagca 360 caactttttaaaactttatccacacagcctcaaccagctgacttaagacgtcatctttcc 420 tttcctttaccagccatggttatatcagccttgatgggtgttcgttacgaagatcatgct 480 tttttcgcaggtctgtcagatgaagtaatgactcaccagcatgaatccggacccaggagc 540 gccagtcgtcttgcatgggaagaattgagagcatatataagagatcgtatgcgtgaaaag 600 agacaggatccaggtgataacctgctgactgatttattggcggcggtggatcaaggtaaa 660 gcaagtgaagaagaagctattggactggcagctggcatgttagttgctgggcatgagagc 720 acagcagctcaaatagaatgtggtctattagcgatgtttagacatccacagcaaagagaa 780 aggcttgttgctgacccaagtttattagataaaaccgtcgaggaaattttaagaatgtac 840 ccacctggggctggttgggatgggattatgagataccctagaacagatgtgactatcgct 900 ggtgtacacatccctgctgaatctaaagtccttgtgggattacctgctacctcttttgat 960 ccgaggcagtttgatgatcctgagatatttgacatcggtagagacgagaaacctcatctg 1020 gctttttcctacggtccgcactattgcatcggcggtgcattggctagattggaattgaag 1080 gcagttttcggatctattttccaaagatttcctggtttaagattagcagttgctccagaa 1140 gaattacgtctgagaaaagagattattacaggcggatttgaggagatgccagtgctgtgg 1200 taa 1203 SEQIDNO:8 MSEQPLPTLPMWRVDHIEPSPEMLALRANGPIHRVRFPSGHEGWWVTGYDEAKAVLSDTA 60 FRPAGMPPAAFTPDSVILGSPGWLVSHEGGEHTRLRTIVAPAFGDSRIKLLAQQVEAIAA 120 QLFKTLSTQPQPADLRRHLSFPLPAMVISALMGVRYEDHAFFAGLSDEVMTHQHESGPRS 180 ASRLAWEELRAYIRDRMREKRQDPGDNLLTDLLAAVDQGKASEEEAIGLAAGMLVAGHES 240 TAAQIECGLLAMFRHPQQRERLVADPSLLDKTVEEILRMYPPGAGWDGIMRYPRTDVTIA 300 GVHIPAESKVLVGLPATSFDPRQFDDPEIFDIGRDEKPHLAFSYGPHYCIGGALARLELK 360 AVFGSIFQRFPGLRLAVAPEELRLRKEIITGGFEEMPVLW 400 SEQIDNO:9 atgagcgaacagcctttacctatgttgcccatgtggagagtagatcacatcgagccatca 60 cccgaaatgttagcactgagagcaaaagggcctatacaccgtgttagatttccgtctggt 120 gatgaaggttggtgggtgaccggttacgacgaagcaaaagcggtgttatcagatgctgcg 180 tttaggcccagcggtatgccccctgcagctgtgactagtgctacagtcatattgggttca 240 ccgggctggttggggagccatgagggttctgaacacgctagactgagaaccatcgtagcc 300 cctgccttttcttcaggtagagtcaaattgttagcacaacaagtggaagccattgcagct 360 gagttattcgaaaccttggcggcccaaccacagccagcagacctgagaagacacttgagt 420 tttccgcttcccgctatggtgatttctgccttaatgggcgtgctgtatgaagaccatgcc 480 tttttcgcccgtttgagtgataaagtaatgacccatcaatatgaaagtggtcctcgttca 540 gcggcacgtttggcgtgggaggagttaagagcatatattagaggcaagatgcgtgataag 600 agacaagaccccggagacaacttgctaaccgatttgcttgcagcagtggatcaaggtaaa 660 gcaacggaagaggaagcaataggattggcagcaggtatgttggtcgcaggacatgaaacc 720 acagtggcgcagattgaattcggtctattggctatgtttaggcatccacagcaaagagag 780 agattagttggcgacccgagtttggtcgataaggcagtagaggagattttgagaatgtat 840 cctcctggtgccggatgggatggtattatgaggtatccaagaacagacgtcactattgca 900 ggagtacatatcccagccgagagcaaggtcctggttggtttgccggctacatcctttgat 960 cccagacattttgacgatccagaaatttttgatgtgggaagagaggaaaaacctcatcta 1020 gccttctcatatggaccacattactgcatcggagtggagttggcacgtttggaattgaga 1080 gttgtctttggttcaatattccagagatttccagcgcttagactggcggtggccccagag 1140 gaattgaaattgagaaaggccatcattactggcggttttgaagcttttcccgttttatgg 1200 tga 1203 SEQIDNO:10 MSEQPLPMLPMWRVDHIEPSPEMLALRAKGPIHRVRFPSGDEGWWVTGYDEAKAVLSDAA 60 FRPSGMPPAAVISATVILGSPGWLGSHEGSEHARLRTIVAPAFSSGRVKLLAQQVEAIAA 120 ELFETLAAQPQPADLRRHLSFPLPAMVISALMGVLYEDHAFFARLSDKVMTHQYESGPRS 180 AARLAWEELRAYIRGKMRDKRQDPGDNLLTDLLAAVDQGKATEEEAIGLAAGMLVAGHET 240 TVAQIEFGLLAMFRHPQQRERLVGDPSLVDKAVEEILRMYPPGAGWDGIMRYPRTDVTIA 300 GVHIPAESKVLVGLPATSFDPRHFDDPEIFDVGREEKPHLAFSYGPHYCIGVELARLELR 360 VVFGSIFQRFPALRLAVAPEELKLRKAIITGGFEAFPVLW 400 SEQIDNO:11 atggcggaattagatacgttagatatcgttgttttaggcgctttattgttgggcacatta 60 gcgtattttacgaagggcacattatggggtgtcactaaggatccttatgcaaacgctttc 120 gcaaatgctaacggagctaaagccggcagatcaagaaatatcgttgaaaaaatggatgaa 180 tctggtaaaaactgcgtcatattctacggttctcaaactggaacggcagaggattacgca 240 tcaagattagcgaaagaaggaaagtcaagattcgggttagggactatggttgcagattta 300 gaagaatatgattatgataaccttgatacaatgagcggcgataaggttgccatgtttgtt 360 cttgctacctatggcgagggcgaaccaactgacaacgcagtagagttttatgaatttatt 420 actggtgaaggggttgcttttagtgaaggaaacgatccccccttaggcaatctgaactac 480 gtggcctttggactggggaacaatacttatgaacactacaattcaatggtcagaaatgtc 540 gataaagcccttaggaatctgggtgctcataggatcggagaggctggtgaaggcgatgac 600 ggtgctggcacaatggaagaagattttctagcatggaaggaaccaatgtgggccgcctta 660 gctgacaaaatgggtttggaggaaagggaagcagtatatgaccctgtgttcagtatcgtt 720 gatcgtgataatttgactcctgaaagcccagaagtctatttgggtgaacctaataaaatg 780 catttagaggatgcggtcaagggcccatttaattctcataatccatatatagcaccaata 840 gctgaatctagagaattgtttagtgttaaagacaggaattgcatccatatggaaattgac 900 atagacggttcaaatttgagctatcaaactggggatcatgtggctatttggcctaccaac 960 ccaggagatgaagtggatagatttttagacatcattgatttaaaggataaacgtgacaag 1020 gttataggagtgaaagcacttgaaccaactgcaaaggtcccttttccaacaccaacaaca 1080 tatgacgttatcgccaggtatcatttagaaatctgtgcaccggtctctagacagtttgtg 1140 tccactctagcagcattctccccaaatgatgaggtaaaagcagaaatgactagattgggt 1200 aacgataaggattattttcatgataagacgggcccacattattataatatcgcccgtttt 1260 ctagctgcggttggtaagggcgagaaatggtcaaatatccctttttctgtttttgtcgaa 1320 ggtttaacgaaattacaaccaagatattattcaatctcctcttcaagcctagtacaacca 1380 aaaaaaatatcaataacggcagtaattgagtcacaggttatacctgccaggcaagatcca 1440 tttagaggtgtagctacgaactacttatttgcattgaaacagaagcaaaacggtgatcca 1500 aatccctccccatttggacatacttatgcattaaacggccctagaaataaatttgacggt 1560 atacacgtccccgtccacgtaaggcactccaatttcaaactaccgagcgatccagcaaaa 1620 ccagttattatggttggtccaggaactggagtggctccgtttagaggtttcatccaagag 1680 agagctaaacaggcccaggatggggccacagtaggccgtactatcttgttcttcggttgc 1740 caacgtaggtccgaagattttttgtacgaaagtgaatggaaagaatacaaggaagttcta 1800 ggagatacccttgagatagtcactgccttctccagggaaacatcaaagaaagtttatgtg 1860 cagcacaggttgaaagagagatccaaagaaatcggagaactattatcacagaaagcatac 1920 ttttatgtgtgtggcgatgctgctcatatggctagagaagttaatactgtattggctcaa 1980 attatcgctgaatctaggggtgtaagtgaagccaagggtgaagagattgttaaaaatatg 2040 agggctgctaatcagtaccaagttaggagggggaacaatgtctttttttgggctataagt 2100 ggttctattgatatgacggccaataccgccaacttacaagaagatgtgtggagctga 2157 SEQIDNO:12 MAELDTLDIVVLGALLLGTLAYFTKGTLWGVTKDPYANAFANANGAKAGRSRNIVEKMDE 60 SGKNCVIFYGSQTGTAEDYASRLAKEGKSRFGLGTMVADLEEYDYDNLDTMSGDKVAMFV 120 LATYGEGEPTDNAVEFYEFITGEGVAFSEGNDPPLGNLNYVAFGLGNNTYEHYNSMVRNV 180 DKALRNLGAHRIGEAGEGDDGAGTMEEDFLAWKEPMWAALADKMGLEEREAVYDPVFSIV 240 DRDNLTPESPEVYLGEPNKMHLEDAVKGPFNSHNPYIAPIAESRELFSVKDRNCIHMEID 300 IDGSNLSYQTGDHVAIWPTNPGDEVDRFLDIIDLKDKRDKVIGVKALEPTAKVPFPTPTT 360 YDVIARYHLEICAPVSRQFVSTLAAFSPNDEVKAEMTRLGNDKDYFHDKTGPHYYNIARF 420 LAAVGKGEKWSNIPFSVFVEGLTKLQPRYYSISSSSLVQPKKISITAVIESQVIPARQDP 480 FRGVATNYLFALKQKQNGDPNPSPFGHTYALNGPRNKFDGIHVPVHVRHSNFKLPSDPAK 540 PVIMVGPGTGVAPFRGFIQERAKQAQDGATVGRTILFFGCQRRSEDFLYESEWKEYKEVL 600 GDTLEIVTAFSRETSKKVYVQHRLKERSKEIGELLSQKAYFYVCGDAAHMAREVNTVLAQ 660 IIAESRGVSEAKGEEIVKNMRAANQYQVRRGNNVFFWAISGSIDMTANTANLQEDVWS 718 SEQIDNO:13 atggcaaccttggttcacgtgggtcactttggtagacccttgtgttcaggacaagctttg 60 cctttgcttctagccggaatcttggcggcagccttagcaatcaaagctgcggcgtggtgc 120 gctcgtaaacgtcatctagcagaaattccattggccaacccaccttcatggttatttttc 180 tctagacctgctgaaagagtagctttggttaggagtgctgctgaagcattgctgcgtgct 240 agagacgatttcccacatggaccttttcgttttctaagtgactggggtgaacttctaatc 300 ttgcctcctgagttcgccgaagaaataagaaatgaacctaaactatcttttgggctagct 360 gcaatgagagataatcatgcgaatatacctggttttgaaactgttagaattgtcggtaga 420 gatgatcaacttttacaagctgttgctagaaaacatctaacaaaacacttggccaaggcc 480 atcgaaccattgtgcgcggaagcaagcctggctctagcagttaatctaggtgagtcacca 540 gactggcaaacagttagattgcaacctgccgtgctggatattattgcaaggctatccagt 600 agagtgtatctgggtgagcaattgtgtagatctcaggactggttggctgttacaaagact 660 tatgccacagcgttttatgctgcatcatccaaattgagaatgtttccaagagctctacgt 720 ccattggtacattggtggatgccagagtgtcgtagactaagagctcaacgtagggcagcc 780 gaagccattatccgtcctttggttaggcgtagacaacaagctaaacaagcggcagcagcc 840 gccgggcatccagcccccgtgtttcatgatgcccttgagtgggctgaacaggaggctgca 900 acagctgccgctgcggccgcagctgggaggtctagatcttgtgatccagttgtatttcaa 960 ttggcactgtccttgctagcaattcacacaacatatgatcttctgcagcaagcaatgact 1020 gatctagcttctaatccacaatacataggtcctttaagagatgaagtcgcaagagttgtt 1080 gggcaagacgggtggagtaaagcttctttgtataagatgaagcttttggatagtgccctt 1140 aaggaaactcaaaggttaaaacccggttctattgttaccatgaggcgtgttgctactgat 1200 gatgttgctttgtcatccggtcttgtgttgaaaaaaggtaccagggttaacgtcgataat 1260 aggagaatgactgacgcggcagtttatgccgatcctagagtttacaacccctggagattt 1320 tatcaaatgaggctgcaacccggtaaagaacatgtagctcaattggtttctacctcccca 1380 gatcacttgggatttggccacggcttgcattcatgtcctggtaggttcttcgctgcgaat 1440 gaagttaaggtagctttgggtcatatgttgttaaagtatgactggaagcttgctcctgcg 1500 acggacaagacaccagattgtagaggaatgttggcaaaagctagcccaactactgatgtg 1560 atgatcaggaggagacatgacgaggctgatacaggcgctgcagcaagagaatag 1614 SEQIDNO:14 MATLVHVGHFGRPLCSGQALPLLLAGILAAALAIKAAAWCARKRHLAEIPLANPPSWLFF 60 SRPAERVALVRSAAEALLRARDDFPHGPFRFLSDWGELLILPPEFAEEIRNEPKLSFGLA 120 AMRDNHANIPGFETVRIVGRDDQLLQAVARKHLTKHLAKAIEPLCAEASLALAVNLGESP 180 DWQTVRLQPAVLDIIARLSSRVYLGEQLCRSQDWLAVTKTYATAFYAASSKLRMFPRALR 240 PLVHWWMPECRRLRAQRRAAEAIIRPLVRRRQQAKQAAAAAGHPAPVFHDALEWAEQEAA 300 TAAAAAAAGRSRSCDPVVFQLALSLLAIHTTYDLLQQAMTDLASNPQYIGPLRDEVARVV 360 GQDGWSKASLYKMKLLDSALKETQRLKPGSIVTMRRVATDDVALSSGLVLKKGTRVNVDN 420 RRMTDAAVYADPRVYNPWRFYQMRLQPGKEHVAQLVSTSPDHLGFGHGLHSCPGRFFAAN 480 EVKVALGHMLLKYDWKLAPATDKTPDCRGMLAKASPTTDVMIRRRHDEADTGAAARE 537 SEQIDNO:15 atggtcaacaaagaagaaatcaccattccaaccgctgatttgtctccattcttgaaagaa 60 ttggaccagggttcttattcctacgatgatgatgatgacgaccaaaagaaaaaaaaggct 120 gccgccattgaaattattggtaaggcttgttctgagttcggtttcttccaagttgttaat 180 catggtgttccattgcacttgatgcaaaaggctttgttgttgtctaatcagttcttcggt 240 tacccattggacagaaaattgcaagcttctccattgccaggtgctccaatgccagctggt 300 tatggtagacaaccagatcattctccagataagaacgagttctttatgatgttcccacca 360 cattctaccttcaacgtttttccatctcatccacaaggtttcagagaagttgttgaagag 420 ttgttctcttgcttcgttaagaccgcttctgttatcgaaaacatcatcaacgaatgtttg 480 ggtttgcctccaaatttcttgtctgagtacaacaacgatagaaagtgggatttgatgtcc 540 actttcagatacccaaacgcctctgaaattgaaaacgttggtttgagagaacacaaggac 600 gttaacttcattaccttgttgttccaagatgaagtcggtggtttggaagttaagactgaa 660 gatcatcaatggatcccaattatcccaaaccagaacaccttggttattaacgttggtgat 720 gttatccaggtcttgtccaatgatagatacaagtctgcttcccacagagttgttagacaa 780 gaaggtagagaaagacactcttacgctttcttctacaatatcggtggtgataagttggtt 840 caaccattgccacatttcaccacccatattgatcaaccaccaaactacaagtccttcatc 900 tacaaagaatacttgcagttgaggttgagaaacaagactcatccaccatcaaacccacaa 960 gatatcatcaacatctcttactactctaccacttaa 996 SEQIDNO:16 MVNKEEITIPTADLSPFLKELDQGSYSYDDDDDDQKKKKAAAIEIIGKACSEFGFFQVVN 60 HGVPLHLMQKALLLSNQFFGYPLDRKLQASPLPGAPMPAGYGRQPDHSPDKNEFFMMFPP 120 HSTFNVFPSHPQGFREVVEELFSCFVKTASVIENIINECLGLPPNFLSEYNNDRKWDLMS 180 TFRYPNASEIENVGLREHKDVNFITLLFQDEVGGLEVKTEDHQWIPIIPNQNTLVINVGD 240 VIQVLSNDRYKSASHRVVRQEGRERHSYAFFYNIGGDKLVQPLPHFTTHIDQPPNYKSFI 300 YKEYLQLRLRNKTHPPSNPQDIINISYYSTT 331 SEQIDNO:17 atgatcacctcctacgcaggttcccaacttttatctttttatgtcacaatatttatcttt 60 acattagtaccttgggctataagattgttctggccaaaacttagaaagggcagtgtcgtt 120 ccattggctaatccacctgagagcttgttcggtaccggtaaaacaaggcgtagctttgta 180 aaattaagccgtgaaattttagctaaagcaaggaacttattcccagacgaaccttttaga 240 ctgattactgactggggcgaggtgcttatccttcctccggagttcgctgatgagatccgt 300 aatgatccgcgtctgtcattttcaaaggctgccatgcaggataatcacgcaggtattcct 360 ggcttcgaaaccgttgcgcttgtgggtagagaagaccagctgatacaaaaggtggctagg 420 aaacaattgacgaaacatcttagtgccgttattgaaccattgagtagagaatcaactctg 480 gcagtcagtttaaacttcggggaatcaactgaatggcgtagtatcagattaaaacccgca 540 attctggatattatcgctagaatctccagcagaatttatttgggcgatcaattgtgtaga 600 aatgaagcatggttaaaaattactaaaacctatactacaaacttttacacagccagcaca 660 aaccttagaatgttcccgagaccaattagacctcttgcccattggttcttgcctgagtgt 720 agaaaactaagacaagagagaaaggacgctgtcggtatcattactccattgatagagagg 780 cgtcgtgagttacgtagagctgcagtcgcagctggtcaacctctacccgtttttcacgat 840 gcaattgactggagtgaacaggaggccgaggcggcgggcagtgggtccgcatttgatcct 900 gttatttttcaattgacactttctttgctagccatccacaccacctatgacctacttcaa 960 caaactatgatagacttgggaagacacccagaatacattgatcccctacgtcaagaagtc 1020 gttcaattgttaagggaagaaggttggaaaaaaaccactctgttcaaaatgaaattgctg 1080 gattctgctatcaaagaaagtcagagaatgaaaccggggagtattgttactatgagaagg 1140 tatgtcactgaagatataaccttatcatccggattaacacttcataaaggcactagatta 1200 aacgttgataacaggagactagatgacccaagaatctacgaaaatccggaagtctataat 1260 ccatatcgtttttatgatatgaggtccgaagcttctaaggaccatggtgcacagttggta 1320 agtactggtagtaaccatatgggttttgggcatggacaacattcttgtcccggtagattt 1380 ttcgcagctaacgagattaaagtagcgttgtgccatatacttgtaaaatatgattggaaa 1440 ttatgtccaaatactgagacgaaacctgatacaaggggtatgattgctaaatctagtcct 1500 gtcacggatattctaattaagagaagggaaagcgtggaattggatttagaagcaatgtaa 1560 SEQIDNO:18 MVNKEEITIPTADLSPFLKELDQGSYSYDDDDDDQKKKKAAAIEIIGKACSEFGFFQVVN 60 HGVPLHLMQKALLLSNQFFGYPLDRKLQASPLPGAPMPAGYGRQPDHSPDKNEFFMMFPP 120 HSTFNVFPSHPQGFREVVEELFSCFVKTASVIENIINECLGLPPNFLSEYNNDRKWDLMS 180 TFRYPNASEIENVGLREHKDVNFITLLFQDEVGGLEVKTEDHQWIPIIPNQNTLVINVGD 240 VIQVLSNDRYKSASHRVVRQEGRERHSYAFFYNIGGDKLVQPLPHFTTHIDQPPNYKSFI 300 YKEYLQLRLRNKTHPPSNPQDIINISYYSTT 331 SEQIDNO:19 atgtctccaactcaatctactactactccagctacaaaaccagttatggcttctattcca 60 tattactccggtccttttaatccaccagataccatttctgctgtttccactaagagatac 120 tgtgattggagatccgttaacatcaacgatgttagatcttccactaaggatttcaccttg 180 gataagaatggtttccagtacatgaagcactcttcagctttatcttctccaccacatact 240 ttggcttcatggaaagataacgaaaccagaaagagagttaacgacgccgaaattttggaa 300 ttgggtaaagctgttactggtgccaaaaaggttttggttgttttggctattggtagagat 360 gctgcttttactgatccattggatcaaacttctagaccagatgtctacggtaatcaaact 420 gatactttgccagctactagacagttgggtttttatggtggtgctaatattggtccagct 480 agaaaacctcatgttgattggggtccagatggtgttagatctattttgagaaactggtcc 540 catgaattggctgatgaagccaaggatattattgatgctgaagatgaagccatctctttg 600 ccaggtggtattgaagaaaattacaagggtagaagatggggcttgtataatacttggagg 660 ccattgaaaccagtcagaagagatccattggcttgtgttgatttcgtgtcctctaagaat 720 gataagtccgccattttgttgagaaagatcccaggtattcatggtccatgtactgttgat 780 gctttgtttactccagctaatccaaaacatgaatggtactggatgtctgatcaacaacca 840 gatgatatcttgttcatgaagatcttcgattccgctcacgaaagagatccaaaaactatt 900 gctggtggtgttcatcactgttcttttcatcatccaggtactgaagatgaggaagtcaga 960 gaatctttggagactaagtttatggctttctggtaa 996 SEQIDNO:20 MSPTQSTTTPATKPVMASIPYYSGPFNPPDTISAVSTKRYCDWRSVNINDVRSSTKDFTL 60 DKNGFQYMKHSSALSSPPHTLASWKDNETRKRVNDAEILELGKAVTGAKKVLVVLAIGRD 120 AAFTDPLDQTSRPDVYGNQTDTLPATRQLGFYGGANIGPARKPHVDWGPDGVRSILRNWS 180 HELADEAKDIIDAEDEAISLPGGIEENYKGRRWGLYNTWRPLKPVRRDPLACVDFVSSKN 240 DKSAILLRKIPGIHGPCTVDALFTPANPKHEWYWMSDQQPDDILFMKIFDSAHERDPKTI 300 AGGVHHCSFHHPGTEDEEVRESLETKFMAFW 331 SEQIDNO:21 atgccacataaggatactccattggaatctccagttggtaagaatgttactgctaccatt 60 gcttatcattctggtccagctttgccaacttctccaattgctggtgttactactttacaa 120 gattgcacccaacaagttgttgccgttactgatattagaccatccgtttcttcattcacc 180 ttggatggtaatggtttccaagttgtcaaacatgcttctgctgttggttctcctccttac 240 aatcattcttcttggactgatccagtcgtcagaaaagaagtttacgatccagaaattatc 300 gaattggccaagtctttgactggtgccaaaaaggttatgattttgttggcctcttctagg 360 aacgtcccttttaaagaaccagaattggctccaccatatccaatgccaggtaaatctaat 420 tccggttctaaagaaggtggcgctaatccagctaatgaattgccaactactagagctaag 480 ggtttccaaaaaggtgaagaagaaggtccagttagaaaaccacacaaagattggggtcca 540 tctggtgcttggaatactttgagaaattggtcccaagaattgatcgatgaagccggtgat 600 attatcaaagctggtgatgaagctgctaaattgccaggtggtagagctaagaattatcaa 660 ggtagaagatgggccttgtatacaacttggaggccattgaaaccagttaagagggatcca 720 atggcttatgttgattattggactgctgatggtgaagatggtgtttcattttggagaaat 780 ccaccaggtgttcatggtacttttgaatccgatgttttgttgactaaggctaacccaaaa 840 cataagtggtactggatttctgatcaaaccccagatgaagtcttgttgatgaagattatg 900 gacaccgaatctgaaaaggatggttctggtattgctggtggtgttcatcactgttctttt 960 catttgccaggtactgaaaaagaagaggtcagagaatccatcgaaactaagtttattgcc 1020 ttctggtaa 1029 SEQIDNO:22 MPHKDTPLESPVGKNVTATIAYHSGPALPTSPIAGVTTLQDCTQQVVAVTDIRPSVSSFT 60 LDGNGFQVVKHASAVGSPPYNHSSWTDPVVRKEVYDPEIIELAKSLTGAKKVMILLASSR 120 NVPFKEPELAPPYPMPGKSNSGSKEGGANPANELPTTRAKGFQKGEEEGPVRKPHKDWGP 180 SGAWNTLRNWSQELIDEAGDIIKAGDEAAKLPGGRAKNYQGRRWALYTTWRPLKPVKRDP 240 MAYVDYWTADGEDGVSFWRNPPGVHGTFESDVLLTKANPKHKWYWISDQTPDEVLLMKIM 300 DTESEKDGSGIAGGVHHCSFHLPGTEKEEVRESIETKFIAFW 342 SEQIDNO:23 atgccacatcaacaaactccattggaatctccagttggtaagaatgttactgctaccatt 60 gcttaccataatggtccagctttgccaacttctccaattgctggtgttactactttggaa 120 gattgcacccaacatgttgttgctgttactgatattagaccatccgtttcttcattcacc 180 ttggatggtaatggtttccaagttgttaagcacgtttccgaagtttcttctcctccatac 240 aatcattcttcatggactgatccagtcgtcagaaaagaagtttacgatccagaaattatc 300 gaattggccaagtctgttactggtgccaaaaaggttatgattttgttggcttctgctagg 360 aacgtcccttttaaagaaccagaattggctccaccatatccaatgccatctaaaggtggt 420 aaagaaggtggcgctggtcaaactgttcaaggtcaacatgaattgccaactactagagct 480 aagggttttcaaaagggtgaagaagaaggtccagttagaaaaccacataaggattggggt 540 ccatctggtgcttggaatactttgttgaattggtcccaagaattgatcgatgaagccgat 600 gatattatcaaggctggtgatgaagctgctgaattgccaggtggtagagctaagaattat 660 caaggtagaagatgggccttgtatacaacttggaggccattgaaaccagttaagagggat 720 ccaatggcttttgttgattattggactgctgatgaagaggacggtgtttcattttggaga 780 aatccaccaggtgttcatggtacttttgaatccgatgttttgttgactagagctaaccca 840 aaacataagtggtactggatttctgatcaaaccccagatgaagtcttgttgatgaagatt 900 atggacaccgaatctgaaaaggacggttctgatattgctggtggtgttcattactgttct 960 ttccatttgccagtctccgaaaaagaagaagtcagagaatccatcgaaacgaagtttatt 1020 gctttctggtaa 1032 SEQIDNO:24 MPHQQTPLESPVGKNVTATIAYHNGPALPTSPIAGVTTLEDCTQHVVAVTDIRPSVSSFT 60 LDGNGFQVVKHVSEVSSPPYNHSSWTDPVVRKEVYDPEIIELAKSVTGAKKVMILLASAR 120 NVPFKEPELAPPYPMPSKGGKEGGAGQTVQGQHELPTTRAKGFQKGEEEGPVRKPHKDWG 180 PSGAWNTLLNWSQELIDEADDIIKAGDEAAELPGGRAKNYQGRRWALYTTWRPLKPVKRD 240 PMAFVDYWTADEEDGVSFWRNPPGVHGTFESDVLLTRANPKHKWYWISDQTPDEVLLMKI 300 MDTESEKDGSDIAGGVHYCSFHLPVSEKEEVRESIETKFIAFW 343 SEQIDNO:25 atgccacacaaggataacttgttggaatctccagttggtaaatctgttactgctaccatt 60 gcttatcattctggtccagctttgccaacttctccaattgctggtgttactactttacaa 120 gattgcacccaacaagctgttgctgttactgatattagaccatccgtttcttcattcacc 180 ttggatggtaatggtttccaagttgttaagcacacttctgctgttggttcacctccatat 240 gatcattcttcatggactgatccagtcgtcagaaaagaagtttacgatccagaaattatc 300 gaattggccaagtctttgactggtgccaaaaaggttatgattttgttggcctcttctagg 360 aacgtcccttttaaagaaccagaattggctccaccatatccaatgccaggtaaatcttct 420 tcaggttccaaagaaagagaagctattccagctaatgaattgccaactactagagctaag 480 ggtttccaaaaaggtgaagaagaaggtccagttagaaagccacataaggattggggtcca 540 tctggtgcttggaatactttgagaaattggtcccaagaattgatcgatgaagccggtgat 600 attatcaaagctggtgatgaagctgctaaattgccaggtggtagagctaagaattatcaa 660 ggtagaagatgggccttgtatacaacttggaggccattgaaaactgttaagagggatcca 720 atggcttacgttgattattggactgctgatgaagaggatggtgtttcattttggagaaat 780 ccaccaggtgttcatggtacttttgaatccgatgttttgttgactaaggctaacccaaaa 840 cataagtggtactggatttctgatcaaaccccagatgaagtcttgttgatgaagattatg 900 gacaccgaatctgaaaaggacggttctgaaattgctggtggtgttcatcactgttctttt 960 catttgccaggtactgaaaaagaagaggtcagagaatccatcgaaactaagtttattgcc 1020 ttctggtaa 1029 SEQIDNO:26 MPHKDNLLESPVGKSVTATIAYHSGPALPTSPIAGVTTLQDCTQQAVAVTDIRPSVSSFT 60 LDGNGFQVVKHTSAVGSPPYDHSSWTDPVVRKEVYDPEIIELAKSLTGAKKVMILLASSR 120 NVPFKEPELAPPYPMPGKSSSGSKEREAIPANELPTTRAKGFQKGEEEGPVRKPHKDWGP 180 SGAWNTLRNWSQELIDEAGDIIKAGDEAAKLPGGRAKNYQGRRWALYTTWRPLKTVKRDP 240 MAYVDYWTADEEDGVSFWRNPPGVHGTFESDVLLTKANPKHKWYWISDQTPDEVLLMKIM 300 DTESEKDGSEIAGGVHHCSFHLPGTEKEEVRESIETKFIAFW 342 SEQIDNO:27 atggccgatcaagaaattactactgctccaccatcttctccattggttccattggatttt 60 tcttcatctcacgaaaccgttccagaatcccatatttgggttgattccattgaattgtct 120 ccagctatggatttggacgagaaattgtctttgccagttatcgatttgttggatgatacc 180 actgcctctgaattgattggtaaagcttgtcaacaatggggtatgttccaattgattaac 240 catggtgttccaaagtccattattgccgaaactgaagatgaagctagaaggttgtttgct 300 ttgccaactactcaaaagatgaagacttttggtccaggtaatactggttatggtatggtt 360 ccattgtccaagtaccattctaaatccatgtggcatgaaggtttcaccatttttggttct 420 ccattggatgatgctaaaaagttgtggccatctgactacaagagattctgtgatgttatg 480 gaagaataccaaagaaagatgaagggtttggccgatagattgatgagattgatcttgaag 540 ttcttggacatctccgaagaagagatcatgaagttgatgttcactccagaggattcctct 600 aaaatctacactgctttgaggttgaacttgtatccaccatgtccagatccagatagagtt 660 gttggtatggcttctcatactgatacttcattcttcaccattatccaccaagctagaaat 720 gatggcttgcaaatctttaaggatgaagctggttgggttccattatctccaacatctggt 780 actttgatggttaacgttggtgacttgttgcagattttgtctaatggtagattcccatcc 840 atcttgcacagagttatgatccaagaaaagatggaagataggttgtccttggcttacttt 900 tacactccaccaccacatatctatattgctccatactgtaagccattgtccgaatctcca 960 caaatcccattatacagatgtgtcaccgtcaaagaatactccacttctaagtctaacaac 1020 aacttcaagggtttgtctaccgtcaagatctcctctttgatttga 1065 SEQIDNO:28 MADQEITTAPPSSPLVPLDFSSSHETVPESHIWVDSIELSPAMDLDEKLSLPVIDLLDDT 60 TASELIGKACQQWGMFQLINHGVPKSIIAETEDEARRLFALPTTQKMKTFGPGNTGYGMV 120 PLSKYHSKSMWHEGFTIFGSPLDDAKKLWPSDYKRFCDVMEEYQRKMKGLADRLMRLILK 180 FLDISEEEIMKLMFTPEDSSKIYTALRLNLYPPCPDPDRVVGMASHTDTSFFTIIHQARN 240 DGLQIFKDEAGWVPLSPTSGTLMVNVGDLLQILSNGRFPSILHRVMIQEKMEDRLSLAYF 300 YTPPPHIYIAPYCKPLSESPQIPLYRCVTVKEYSTSKSNNNFKGLSTVKISSLI 354 SEQIDNO:29 atggcttctaccttgtctcaagttttcagagataatccattgccattgaaccacatcatc 60 ccattggattttacctctgttcattccttgccagaatctcatgtttggccagcttttgat 120 ggttttccatttggtactacttacccaggtgaaaagttctccattccaatcatcgatttg 180 atggatccaaatgctgctcaattggttggtcatgcttgtgaaaaatggggtgcttttcaa 240 ttgacttctcatggtttgccatccatcttgactgatgatgttgaatctcaaaccagaagg 300 ttgtttgctttgccagctcacgaaaaaatgaaggctttgagattgccatctggtggtact 360 ggttatggtcaagctagaatttctccattctacccaaagttcatgtggcatgaaggtttc 420 actattatgggttctgctgttgatcatgctagaaaattgtggccagatgattacaagggt 480 ttctgtgatgttatggaagattaccaaaagaagatgaaggaattggccgaatccttgttg 540 catatcttcttggaatccttggacatctccaaagaagagtacagatctaccactattcaa 600 agaggtcataaggcttgtaataccgccttgcaattgaattcttatccaccatgtccagat 660 ccaaatagagctatgggtttggctccacatactgattctttgttgttcaccatcgttcat 720 caatctcacacctccggtttacaaattttgagagatggtgttggttggatcactgttttt 780 ccattggaaggtgctttggttgttaacgttggtgatttgttgcacatcttgtctaatggt 840 agatacccatctgttttacacagagccgttgttaatcaagccgaacacagaatttctttg 900 gcttacttttatggtccaccagccgattctttgatttctccattgtgtaacttggtttct 960 tccggtcaacaagttgttgctccaagatatagatccgtgtctgtcaaagaatacgtcgat 1020 ttgaaagagaagcacaaagaaaaggccttgtccttgttgagattgtga 1068 SEQIDNO:30 MASTLSQVFRDNPLPLNHIIPLDFTSVHSLPESHVWPAFDGFPFGTTYPGEKFSIPIIDL 60 MDPNAAQLVGHACEKWGAFQLTSHGLPSILTDDVESQTRRLFALPAHEKMKALRLPSGGT 120 GYGQARISPFYPKFMWHEGFTIMGSAVDHARKLWPDDYKGFCDVMEDYQKKMKELAESLL 180 HIFLESLDISKEEYRSTTIQRGHKACNTALQLNSYPPCPDPNRAMGLAPHTDSLLFTIVH 240 QSHTSGLQILRDGVGWITVFPLEGALVVNVGDLLHILSNGRYPSVLHRAVVNQAEHRISL 300 AYFYGPPADSLISPLCNLVSSGQQVVAPRYRSVSVKEYVDLKEKHKEKALSLLRL 355 SEQIDNO:31 atgtccatggttgtccaacaagaacaagaagttgtttttgacgctgctgttttgtctggt 60 caaactgaaattccatcccaattcatttggccagctgaagaatctccaggttctgttgct 120 gttgaagaattggaagttgccttgattgatgttggtgctggtgctgaaagatcttctgtt 180 gttagacaagttggtgaagcttgtgaaagacacggttttttcttggttgttaaccatggt 240 attgaagccgctttgttggaagaggctcatagatgtatggatgcttttttcactttgcca 300 ttgggtgaaaaacaaagagcacagagaagggctggtgaatcttgtggttatgcttcatct 360 tttactggtagattcgcttctaagttgccatggaaagaaactttgtccttcagatattct 420 tccgctggtgatgaagaaggtgaagagggcgttggtgaatatttggttagaaaattgggt 480 gccgaacacggtagaagattgggtgaagtttattctagatactgccacgaaatgtccagg 540 ttgtctttggaattgatggaagttttgggtgagtctttgggtatagttggtgatagaagg 600 cattacttcagaagattcttccagagaaacgactccatcatgagattgaattattaccca 660 gcttgccaaagaccattggatactttgggtactggtccacattgtgatccaacatctttg 720 actatcttgcaccaagatcatgttggtggtttggaagtttgggctgagggaaggtggaga 780 gctattagaccaagaccaggtgctttggttgttaatgttggtgatactttcatggctttg 840 tccaacgctagatatagatcttgcttgcatagagccgttgttaattctactgctccaaga 900 agatctttggcattctttttgtgtccagaaatggataccgttgttagaccacctgaagaa 960 ttggttgatgatcaccatccaagagtttacccagattttacttggagagctttgttggat 1020 ttcacccaaagacattacagagctgatatgaggttgttccaagctttttctgattggttg 1080 aaccatcatagacacttgcaacctactatctactcctga 1119 SEQIDNO:32 MSMVVQQEQEVVFDAAVLSGQTEIPSQFIWPAEESPGSVAVEELEVALIDVGAGAERSSV 60 VRQVGEACERHGFFLVVNHGIEAALLEEAHRCMDAFFTLPLGEKQRAQRRAGESCGYASS 120 FTGRFASKLPWKETLSFRYSSAGDEEGEEGVGEYLVRKLGAEHGRRLGEVYSRYCHEMSR 180 LSLELMEVLGESLGIVGDRRHYFRRFFQRNDSIMRLNYYPACQRPLDTLGTGPHCDPTSL 240 TILHQDHVGGLEVWAEGRWRAIRPRPGALVVNVGDTFMALSNARYRSCLHRAVVNSTAPR 300 RSLAFFLCPEMDTVVRPPEELVDDHHPRVYPDFTWRALLDFTQRHYRADMRLFQAFSDWL 360 NHHRHLQPTIYS 372 SEQIDNO:33 atggattcttccgcttctaccattttgatgccaccaccattggaattgaaagacgaaaga 60 aaaaagggctccgttgttttcgattcctctaagatgcaaaagcaagaaaagttgccaacc 120 gaattcatttggccagatgctgatttggttagagcacaacaagaattgaacgaaccattg 180 atcgatttggacggttttttcaaaggtgatgaagctgctactgctcatgctgctgaattg 240 attagaatggcttgtttgaaccacggtttcttccaagttactaatcacggtgttgatttg 300 gatttgattagagctgctcaagaagatatgggcgcttttttcaaattgccattgtccaga 360 aagttgtccgtcaaaaaaaagccaggtgaattgtctggttattctggtgctcatgctgat 420 agatacacttctaaattgccatggaaagaaaccttgtccttcgtttactgttacgactct 480 ggttctaaacctatggttgctgattacttcaaaaccgctttgggtgaagatttcgaacaa 540 attggttggatctaccaaaagtactgcgacgctttgaaagaattgtccttgggtatcatg 600 cagttgttggctatttctttggatgtcgactcttcctactacagaaagttgtttgaagat 660 ggttactccatcatgaggtgtaattcttacccaccatgtaaagaagctggtttggttatg 720 ggtactggtccacattgtgatccagttgctttgaccattttacaccaagatcaagtcaag 780 ggtttggaagttttcgttgataacaaatggcaatccgttaagccaagaccaggtgctttg 840 gttgttaatattggtgatactttcatggccttgtctaacggcaagtacaagtcttgtatt 900 catagagccgttgtcaacatggacaaagaaagaagatctttgaccttcttcatgtcccca 960 aaggatgataaggttgtttctccaccacaagaattgatcgttagagaaggtcctagaaag 1020 tacccagattttaagtggtctgagttgttggaattcacccaaaaacattacagaccaaac 1080 aacgacaccttgcaatcttttgttgagtggagattatcttcccagaccaagtaa 1134 SEQIDNO:34 MDSSASTILMPPPLELKDERKKGSVVFDSSKMQKQEKLPTEFIWPDADLVRAQQELNEPL 60 IDLDGFFKGDEAATAHAAELIRMACLNHGFFQVTNHGVDLDLIRAAQEDMGAFFKLPLSR 120 KLSVKKKPGELSGYSGAHADRYTSKLPWKETLSFVYCYDSGSKPMVADYFKTALGEDFEQ 180 IGWIYQKYCDALKELSLGIMQLLAISLDVDSSYYRKLFEDGYSIMRCNSYPPCKEAGLVM 240 GTGPHCDPVALTILHQDQVKGLEVFVDNKWQSVKPRPGALVVNIGDTFMALSNGKYKSCI 300 HRAVVNMDKERRSLTFFMSPKDDKVVSPPQELIVREGPRKYPDFKWSELLEFTQKHYRPN 360 NDTLQSFVEWRLSSQTK 377 SEQIDNO:35 atggctactactattgccgacgtttttaagtctttcccagttcatattccagcccacaag 60 aatttggatttcgattccttgcatgaattgccagattcttacgcttggattcaaccagat 120 tcttttccatctccaactcataagcaccacaactccattttggattccgattctgattcc 180 gttccattgatcgatttgtctttgccaaatgctgctgctttgattggtaatgcttttaga 240 tcttggggtgccttccaagttattaaccatggtgttccaatttctttgttgcaatccatt 300 gaatcctctgccgatactttgttttctttgccaccatctcataagttgaaggctgctaga 360 actccagatggtatttctggttatggtttggtcagaatctcttcattcttcccaaaaagg 420 atgtggtctgaaggttttactatagtcggttctccattggatcacttcagacaattgtgg 480 ccacatgattaccacaaacattgcgaaatcgttgaagaatacgacagggaaatgagatct 540 ttgtgtggtagattgatgtggttgggtttgggtgaattgggtattactagagatgatatg 600 aagtgggctggtccagatggtgattttaagacttctccagctgctactcaattcaactct 660 tatccagtttgtccagatccagatagagctatgggtttgggtccacatactgatacttca 720 ttattgaccatcgtctaccagtctaacaccagaggtttacaagttttgagagaaggtaag 780 agatgggttactgttgaaccagttgctggtggtttggttgttcaagttggtgatttgttg 840 catattttgaccaatggcttgtacccatctgctttacatcaagctgttgttaacagaacc 900 agaaagagattgtctgttgcttacgtttttggtccaccagaatctgctgaaatttctcca 960 ttgaaaaagttgttgggtccaactcaaccaccattatacagaccagttacttggactgaa 1020 tacttgggtaaaaaggccgaacatttcaacaacgctttgtctactgttagattgtgtgct 1080 ccaattaccggtttgttggatgttaacgatcactccagagttaaggttggttga 1134 SEQIDNO:36 MATTIADVFKSFPVHIPAHKNLDFDSLHELPDSYAWIQPDSFPSPTHKHHNSILDSDSDS 60 VPLIDLSLPNAAALIGNAFRSWGAFQVINHGVPISLLQSIESSADTLFSLPPSHKLKAAR 120 TPDGISGYGLVRISSFFPKRMWSEGFTIVGSPLDHFRQLWPHDYHKHCEIVEEYDREMRS 180 LCGRLMWLGLGELGITRDDMKWAGPDGDFKTSPAATQFNSYPVCPDPDRAMGLGPHTDTS 240 LLTIVYQSNTRGLQVLREGKRWVTVEPVAGGLVVQVGDLLHILTNGLYPSALHQAVVNRT 300 RKRLSVAYVFGPPESAEISPLKKLLGPTQPPLYRPVTWTEYLGKKAEHFNNALSTVRLCA 360 PITGLLDVNDHSRVKVG 377 SEQIDNO:39 atgcacgttgttacttctacacctgaagctagacatgatggtgcacctttggtttttgat 60 gcttctgttttgagacaccaacacaacattccaaagcaattcatttggccagatgaagaa 120 aaaccagctgctacttgtccagaattggaagttccattgattgacttgtctggtttcttg 180 tctggtgaaaaagatgctgctgctgaagctgttagattggttggtgaagcttgtgaaaaa 240 cacggttttttcttggttgttaaccacggtgttgacagaaagttgattggtgaagctcat 300 aagtacatggacgaattctttgagttgccattgtcccaaaaacaatccgctcaaagaaaa 360 gctggtgaacattgtggttacgcttcatcttttactggtaggttctcttctaaattgcca 420 tggaaagaaaccttgtcctttagatttgctgccgacgaatctttgaacaacttggtcttg 480 cattacttgaacgataagttgggtgatcaattcgctaagttcggtagagtttaccaagat 540 tactgtgaagctatgtccggtttgtctttgggtatcatggaattgctaggtaagtctttg 600 ggtgttgaagaacaatgcttcaagaacttcttcaaggacaacgactccatcatgagattg 660 aatttttacccaccatgccaaaagccacatttgactttgggtactggtccacattgtgat 720 ccaacatctttgactatcttgcaccaagatcaagtcggtggtttacaagtttttgttgat 780 aaccagtggagattgatcaccccaaattttgatgctttcgttgttaacatcggtgatacc 840 tttatggctttgtctaacggtagatacaagtcctgcttgcatagagctgttgttaactct 900 gaaagaacgagaaagtctttggcattcttcttgtgtccaagaaacgataaggttgttaga 960 ccaccaagagaattggttgatactcaaaacccaagaagatacccagatttcacttggtct 1020 atgttgttgagattcacccaaactcattacagagctgatatgaagactttggaagctttt 1080 tctgcttggttgcaacaagaacaacaagagcagcaagaacaacagttcaacatctga 1137 SEQIDNO:40 MHVVTSTPEARHDGAPLVFDASVLRHQHNIPKQFIWPDEEKPAATCPELEVPLIDLSGFL 60 SGEKDAAAEAVRLVGEACEKHGFFLVVNHGVDRKLIGEAHKYMDEFFELPLSQKQSAQRK 120 AGEHCGYASSFTGRFSSKLPWKETLSFRFAADESLNNLVLHYLNDKLGDQFAKFGRVYQD 180 YCEAMSGLSLGIMELLGKSLGVEEQCFKNFFKDNDSIMRLNFYPPCQKPHLTLGTGPHCD 240 PTSLTILHQDQVGGLQVFVDNQWRLITPNFDAFVVNIGDTFMALSNGRYKSCLHRAVVNS 300 ERTRKSLAFFLCPRNDKVVRPPRELVDTQNPRRYPDFTWSMLLRFTQTHYRADMKTLEAF 360 SAWLQQEQQEQQEQQFNI 378 SEQIDNO:41 atggctaccgaatgtattgctactgttccacaaatcttctccgagaacaagaccaaagaa 60 gattcctctattttcgacgccaagttgttgaatcaacattcccatcatatcccacaacaa 120 ttcgtttggccagatcacgaaaaaccatctactgatgttcaaccattgcaagttccattg 180 attgatttggctggtttcttgtctggtgattcttgtttggcttctgaagctactagattg 240 gtttctaaagctgctaccaaacacggctttttcttgattactaatcacggtgttgacgaa 300 tccttgttgtctagagcttacttgcatatggactcatttttcaaagctccagcttgcgaa 360 aaacaaaaggctcaaagaaaatggggtgaatcttctggttacgcttcttcatttgttggc 420 agattctcttctaaattgccatggaaagaaaccttgtccttcaagttttctccagaagaa 480 aagatccattcccaaaccgttaaggacttcgtgtctaaaaagatgggtgatggttacgaa 540 gatttcggtaaggtttatcaagaatacgctgaagctatgaacaccttgtccttgaagatc 600 atggaattgctaggtatgtctttgggtgtcgaaagaaggtacttcaaagaattcttcgag 660 gactccgattccatcttcagattgaattattacccacaatgcaagcaaccagaattggct 720 ttgggtactggtccacattgtgatccaacatctttgactatcttgcaccaagatcaagtc 780 ggtggtttacaagttttcgttgataacaagtggcaatccattccaccaaatccacatgct 840 ttcgttgttaacattggtgatactttcatggctttgaccaacggtagatacaaatcttgc 900 ttgcatagagccgttgtcaactctgaaagagaaagaaagactttcgcattcttcttgtgt 960 ccaaagggtgaaaaagttgttaagccacctgaagaattggttaacggtgttaagtctggt 1020 gaaagaaagtacccagatttcacttggtctatgttcttggaattcacccaaaaacattac 1080 agagccgacatgaacactttggacgaattttctatttggttgaagaacagaagatccttt 1140 taa 1143 SEQIDNO:42 MATECIATVPQIFSENKTKEDSSIFDAKLLNQHSHHIPQQFVWPDHEKPSTDVQPLQVPL 60 IDLAGFLSGDSCLASEATRLVSKAATKHGFFLITNHGVDESLLSRAYLHMDSFFKAPACE 120 KQKAQRKWGESSGYASSFVGRFSSKLPWKETLSFKFSPEEKIHSQTVKDFVSKKMGDGYE 180 DFGKVYQEYAEAMNTLSLKIMELLGMSLGVERRYFKEFFEDSDSIFRLNYYPQCKQPELA 240 LGTGPHCDPTSLTILHQDQVGGLQVFVDNKWQSIPPNPHAFVVNIGDTFMALTNGRYKSC 300 LHRAVVNSERERKTFAFFLCPKGEKVVKPPEELVNGVKSGERKYPDFTWSMFLEFTQKHY 360 RADMNTLDEFSIWLKNRRSF 380 SEQIDNO:43 atgccatctagaccatcaagagtcgtcaaagaacaacatccaactaagaagtccttcttg 60 gacttggaatctttgaacgaattgccagattcttttgcttggggttcttttgaagatcca 120 tgctctattgataacccatctggttatggtccagattctgttccagttatcaacttgcaa 180 gatccacaagctcaacaattggttggtttggcttgtagatcttggggtgttttccaagtt 240 accaaccatggtattcaaaagtccttgttggatgatattgaagctgctggtaagtctttg 300 tttgccttgccagttaatcaaaagttgaaggctgctagatcttcttgtggtgttactggt 360 tacggtccagctggtatttcttcatttttcccaaaaaggatgtggtccgaaggtttcact 420 attttgggttctccattggatcatgctagacaattgtggccaaacaactacaacaagttc 480 tgcgatatcatcgaaaagtaccaaaaagaaatgaaccagttggccaaaaagttgatgcaa 540 ttggttgttggttccttgggtatttccaaccaggatattatgaattgggccgatttgttg 600 gaaggtgctaatggtgctatgcaattgaactcttatccaatcagaccagatccaaataga 660 gctatgggtttggctgctcatactgattctactttgttgaccatcttgcaccaatctaac 720 actaccggtttacaggttttcagagaaagatctggttgggttactgttccaccaatttct 780 ggtggtttggttattaacatcggtgacttgttgcacatcttgtctaatggtagataccca 840 tccgtttaccatagagccatggttaatagagttcagcacagattgtctgttgcttacttg 900 tatggtccagcttcaggtgttagagttcaaccattgccaaaattgattgatgctactcac 960 ccaccattatacagaccagttacttggtctgaatacttgggtatcaagtctgaacatttg 1020 accaaggccttgtccttgattagaatcaaccataacactaacccatccttgactggtttg 1080 attggtaatgatgaacctaagtccatcaacgttgactccgataagactattttggctgtt 1140 ttcggttaa 1149 SEQIDNO:44 MPSRPSRVVKEQHPTKKSFLDLESLNELPDSFAWGSFEDPCSIDNPSGYGPDSVPVINLQ 60 DPQAQQLVGLACRSWGVFQVTNHGIQKSLLDDIEAAGKSLFALPVNQKLKAARSSCGVTG 120 YGPAGISSFFPKRMWSEGFTILGSPLDHARQLWPNNYNKFCDIIEKYQKEMNQLAKKLMQ 180 LVVGSLGISNQDIMNWADLLEGANGAMQLNSYPIRPDPNRAMGLAAHTDSTLLTILHQSN 240 TTGLQVFRERSGWVTVPPISGGLVINIGDLLHILSNGRYPSVYHRAMVNRVQHRLSVAYL 300 YGPASGVRVQPLPKLIDATHPPLYRPVTWSEYLGIKSEHLTKALSLIRINHNTNPSLTGL 360 IGNDEPKSINVDSDKTILAVFG 382 SEQIDNO:45 atgaagtacaccacctgtcagatgaacatttttccatctttgtggtccatgaagaccagt 60 tttagatggccaagaacttctaagtggtcctctgtttcattatacgacatgatgttgaga 120 accgttgctttgttgtctggtagagcttttgttggtttgccattgtgtagagatgaaggt 180 tggttgcaagcttctattggttacactgttcaatgcgtgtctatcagagatcagttgttt 240 acttggtccccagttttgaggccaattattggtccatttttgccatccgttagatctgtt 300 agaaggcatttgagattcgctgctgaaattatggctccattgatttctcaagccttgcaa 360 gacgaaaaacaacatagagctgataccttgttggctgatcaaactgaaggtagaggtact 420 ttcatttcctggttgttgagacatttgccagaagaattgagaaccccagaacaagttggt 480 ttggatcaaatgttggtttcctttgctgctattcataccactactatggctttgacaaag 540 gttgtttgggaattggtaaaaaggccagagtacattgaaccattgagaaccgaaatgcaa 600 gatgtttttggtccagatgctgtttctccagatatctgcattaacaaagaagccttgtcc 660 agattgcacaagttggattctttcatcagagaagttcaaagatggtgtccatctactttc 720 gttactccatctagaagagtcatgaagtctatgactttgtccaacggtatcaagttgcaa 780 agaggtacttctattgcttttccagctcatgccattcacatgtctgaagaaactccaaca 840 ttttccccagatttctcttccgattttgaaaacccatccccaagaattttcgacggtttt 900 agatacttgaacttgaggtccattaagggtcaaggttcacaacatcaagctgctactact 960 ggtccagattacttgattttcaatcatggtaaacatgcctgcccaggtagattttttgct 1020 atctctgaaatcaagatgattttgatcgagttgttggccaagtacgacttcagattggaa 1080 gatggtaaaccaggtccagaattgatgagagttggtactgaaactagattggataccaaa 1140 gctggtttggaaatgagaagaaggtga 1167 SEQIDNO:46 MKYTTCQMNIFPSLWSMKTSFRWPRTSKWSSVSLYDMMLRTVALLSGRAFVGLPLCRDEG 60 WLQASIGYTVQCVSIRDQLFTWSPVLRPIIGPFLPSVRSVRRHLRFAAEIMAPLISQALQ 120 DEKQHRADTLLADQTEGRGTFISWLLRHLPEELRTPEQVGLDQMLVSFAAIHTTTMALTK 180 VVWELVKRPEYIEPLRTEMQDVFGPDAVSPDICINKEALSRLHKLDSFIREVQRWCPSTF 240 VTPSRRVMKSMTLSNGIKLQRGTSIAFPAHAIHMSEETPTFSPDFSSDFENPSPRIFDGF 300 RYLNLRSIKGQGSQHQAATTGPDYLIFNHGKHACPGRFFAISEIKMILIELLAKYDFRLE 360 DGKPGPELMRVGTETRLDTKAGLEMRRR 388 SEQIDNO:47 atggccgaattggataccttggatatcgttgttttgggtgttatcttcttgggtactgtt 60 gcttacttcaccaaaggtaaattgtggggtgttactaaggatccatacgctaatggtttt 120 gctgctggtggtgcttctaaaccaggtagaactagaaatatcgttgaagccatggaagaa 180 tctggtaagaactgtgttgttttctacggttctcaaactggtactgctgaagattatgct 240 tccagattggctaaagaaggtaagagtagattcggtttgaacaccatgattgccgatttg 300 gaagattacgatttcgataacttggataccgtcccatctgataacatcgttatgtttgtt 360 ttggctacctacggtgaaggtgaacctactgataatgctgttgacttctacgaattcatt 420 accggtgaagatgcttctttcaacgaaggtaatgatccaccattgggtaacttgaattac 480 gttgcttttggtttgggtaacaacacctacgaacattacaactccatggttagaaacgtc 540 aacaaggctttggaaaaattgggtgctcatagaattggtgaagctggtgaaggtgatgat 600 ggtgctggtactatggaagaagattttttggcttggaaagacccaatgtgggaagccttg 660 gctaaaaagatgggtttggaagaaagagaagctgtctacgaacctattttcgccattaac 720 gaaagagatgatttgacccctgaagccaatgaagtttatttgggtgaacctaacaagttg 780 cacttggaaggtactgctaaaggtccattcaattctcacaacccatatattgctccaatc 840 gccgaatcttacgaattattctctgctaaggatagaaactgcttgcacatggaaattgac 900 atctctggttctaatttgaagtacgaaaccggtgatcatattgccatttggccaactaat 960 ccaggtgaagaagttaacaagttcttggacatcttggacttgtccggtaaacaacattct 1020 gttgttactgttaaggccttggaacctacagctaaagttccttttccaaatccaactacc 1080 tacgatgccattttgagataccatttggaaatttgcgctccagtctctagacaattcgtt 1140 tctactttggctgcttttgctccaaacgatgatattaaggctgaaatgaacagattgggt 1200 tccgataaggattacttccacgaaaaaactggtccacactactacaacattgctagattt 1260 ttggcctctgtctctaaaggtgaaaagtggactaagattccattctccgctttcattgaa 1320 ggtttgactaagttgcaacctagatattactccatctcctcctcatctttggttcaacct 1380 aagaagatctctattaccgccgttgttgaatcccaacaaattccaggtagagatgatcct 1440 tttagaggtgttgctaccaattacttgttcgccttgaaacaaaagcaaaacggtgatcca 1500 aatcctgctccatttggtcaatcttatgaattgactggtccaagaaacaagtacgatggt 1560 attcatgttccagttcacgttagacactctaactttaagttgccatctgatccaggtaag 1620 ccaattatcatgattggtccaggtactggtgttgctccattcagaggttttgttcaagaa 1680 agagctaagcaagctagagatggtgttgaagttggtaaaaccttgttgttcttcggttgt 1740 agaaagtccactgaagatttcatgtaccaaaaagaatggcaagaatacaaagaagcctta 1800 ggtgacaagttcgaaatgattactgccttctcaagagaaggttctaagaaggtttacgtc 1860 caacacagattgaaagaaagatccaaagaagtctccgatttgttgtctcaaaaggcctac 1920 ttttacgtttgtggtgatgctgctcatatggccagagaagttaatactgttttggcccaa 1980 attatcgctgaaggtagaggtgtatctgaagctaagggtgaagaaatcgttaagaacatg 2040 agatccgccaatcaataccaagtttgctctgattttgttaccttgcactgtaaagaaacc 2100 acctacgctaattccgaattgcaagaagatgtttggtcctaa 2142 SEQIDNO:48 MAELDTLDIVVLGVIFLGTVAYFTKGKLWGVTKDPYANGFAAGGASKPGRTRNIVEAMEE 60 SGKNCVVFYGSQTGTAEDYASRLAKEGKSRFGLNTMIADLEDYDFDNLDTVPSDNIVMFV 120 LATYGEGEPTDNAVDFYEFITGEDASFNEGNDPPLGNLNYVAFGLGNNTYEHYNSMVRNV 180 NKALEKLGAHRIGEAGEGDDGAGTMEEDFLAWKDPMWEALAKKMGLEEREAVYEPIFAIN 240 ERDDLTPEANEVYLGEPNKLHLEGTAKGPFNSHNPYIAPIAESYELFSAKDRNCLHMEID 300 ISGSNLKYETGDHIAIWPTNPGEEVNKFLDILDLSGKQHSVVTVKALEPTAKVPFPNPTT 360 YDAILRYHLEICAPVSRQFVSTLAAFAPNDDIKAEMNRLGSDKDYFHEKTGPHYYNIARF 420 LASVSKGEKWTKIPFSAFIEGLTKLQPRYYSISSSSLVQPKKISITAVVESQQIPGRDDP 480 FRGVATNYLFALKQKQNGDPNPAPFGQSYELTGPRNKYDGIHVPVHVRHSNFKLPSDPGK 540 PIIMIGPGTGVAPFRGFVQERAKQARDGVEVGKTLLFFGCRKSTEDFMYQKEWQEYKEAL 600 GDKFEMITAFSREGSKKVYVQHRLKERSKEVSDLLSQKAYFYVCGDAAHMAREVNTVLAQ 660 IIAEGRGVSEAKGEEIVKNMRSANQYQVCSDFVTLHCKETTYANSELQEDVWS 713 SEQIDNO:49 atggccgaacaacaaatctccaacttgttgtctatgttcaacgccttccataccaatcag 60 aagttggaaatctctgttcaagttaccgattccttccagtatagagatactcctccagat 120 tcttcatcttctgaaggtggttctttgtccagatacgaagaaagaagagtttctttgcca 180 ttggctagaaattctccatctccagatatcgttttccagttgtgtttttctaccgccacc 240 atttctgaattgaaccatagatggaagtcccagagattgaaagttgctgattctccatac 300 aactacatcttgactttgccatccaaaggtattagaggtgccttcattgattctttgaac 360 gtttggttggatgttccagaagataaggcccaagttatcaaggatgttatcgatatgttg 420 cacaactcctcattgatcatcgatgactttcaagatggttccccattgagaagaggtaaa 480 ccatctactcatactgtttttggtccagctcaagctattaacactgctacctacattatc 540 gttaaggccatcgaaagaatccaagagatcgtttctcatgatgctttggctgatattacc 600 ggtactattaccactatctttcaaggtcaagctatggatttgtggtggactgctaacacc 660 atattgcaatccattcaagaatacttgttgatggtcaacgataagactggtgctttgttc 720 agattgtctttggaattattggccttgaactccgaagctccaatttctgattctaccttg 780 gaatccttgtcctccgttgtttctttgttgggtcaatacttccaaatcagggatgactac 840 atgaacttgatcgataacaagtacaccgaccaaaagggtttctgtgaagatttggatgag 900 ggcaaatactccttgactttgattcatgctttacaaaccgactcctccgatttgttgatt 960 aacgttttgtccatgagaagagtccaaggtaaattgactacccaacaaaagatgttggtc 1020 ttggaagttatgaagaccaacggttctttggattggacttctaagttgttgggtatgttg 1080 catacaagagttgttgccgaaatcgactccttggaaatttctatgaagagagataaccca 1140 gctttgagagctttggttgaaagattgaagccagaaacctga 1182 SEQIDNO:50 MAEQQISNLLSMFNAFHTNQKLEISVQVTDSFQYRDTPPDSSSSEGGSLSRYEERRVSLP 60 LARNSPSPDIVFQLCFSTATISELNHRWKSQRLKVADSPYNYILTLPSKGIRGAFIDSLN 120 VWLDVPEDKAQVIKDVIDMLHNSSLIIDDFQDGSPLRRGKPSTHTVFGPAQAINTATYII 180 VKAIERIQEIVSHDALADITGTITTIFQGQAMDLWWTANTILQSIQEYLLMVNDKTGALF 240 RLSLELLALNSEAPISDSTLESLSSVVSLLGQYFQIRDDYMNLIDNKYTDQKGFCEDLDE 300 GKYSLTLIHALQTDSSDLLINVLSMRRVQGKLTTQQKMLVLEVMKTNGSLDWTSKLLGML 360 HTRVVAEIDSLEISMKRDNPALRALVERLKPET 393 SEQIDNO:51 atgaagggtttggttgttgttggtgcttcttatgctggtgttcaagctgctttgactgct 60 agagatgctggttttgctaaacctattgctatcgttggtgatgaaccatgtttgccatat 120 caaagaccaccattgtctaaggattacttgttggataacgcctccgaacaatctttgttc 180 ttgagagataatgctttcttcggtgccaagggtattgaattgattttgggttccagagtt 240 atcgacatcgatttgagagatagaagggccattttggaaagaggttctgttttgggtttc 300 gagcaattggttattgctgctggttctagagctagaagattggaagttccaggtggtcat 360 ttggaaggtgtttgttatttgagatccttgtctgatgctgcccatttgaaaatgagattg 420 aagcaagctgaagatgtcgttattattggtggtggtttcatcggtttggaagttgctgct 480 tctgctacaaaattgggtaagaaggttgttttgattgaagccggtcacagattattggaa 540 agagctacttctccagttgtctcctcttttttgttggatgctcatttgagagccggtgtt 600 gaaattagattgctagaaactgttgctgctttcgaaggtgctagaggtaaattgtctact 660 gtcttgttatcctccggttccaaagttagagctgatatggttgttgtaggtattggtggt 720 attgccaatgatgaattggctagaaaagctggtttgaactgtactaatggtgttaccgtt 780 tctgctcatggtatgactgatgttgatggtgtttttgcttgtggtgattgtgcttaccat 840 ttcaacagattctctaagacttggaccagattggaatctgttcaaaacgctcaagatcaa 900 gctaaagctgctggtttggctattgctggtaaacattctccagatatctctgttccaaga 960 ttctggtctgatcaattcgacttgaagttgcaaactactggtattgctggttcttttgat 1020 gctgctgttgttagaggtactgttgatactggtagattctctaccttctacttcaaggat 1080 ggttgtttgttggctgttgactctattaacagaccaggtgatcaattggttgccagaaga 1140 ttgattgcagctggtgtttctccatctcaaggtgaagctgctgatatttctttcgacttg 1200 aaatctttggtcactccataa 1221 SEQIDNO:52 MKGLVVVGASYAGVQAALTARDAGFAKPIAIVGDEPCLPYQRPPLSKDYLLDNASEQSLF 60 LRDNAFFGAKGIELILGSRVIDIDLRDRRAILERGSVLGFEQLVIAAGSRARRLEVPGGH 120 LEGVCYLRSLSDAAHLKMRLKQAEDVVIIGGGFIGLEVAASATKLGKKVVLIEAGHRLLE 180 RATSPVVSSFLLDAHLRAGVEIRLLETVAAFEGARGKLSTVLLSSGSKVRADMVVVGIGG 240 IANDELARKAGLNCTNGVTVSAHGMTDVDGVFACGDCAYHFNRFSKTWTRLESVQNAQDQ 300 AKAAGLAIAGKHSPDISVPRFWSDQFDLKLQTTGIAGSFDAAVVRGTVDTGRFSTFYFKD 360 GCLLAVDSINRPGDQLVARRLIAAGVSPSQGEAADISFDLKSLVTP 406 SEQIDNO:53 atgagagtcgaaaaccacaacagagatgttatcggtgtttctgttgctccaactcacttg 60 gataatttgtcatctgctatcttgcaacaaggtggtatggctagagtttctttgccaggt 120 gatgttgttacttgggctgctggtggtcatcaaactttgagaagaattttgtccgaccag 180 agattcaacagagattggagacagtggagagctttacaagatggtgaaattccagaagat 240 catccattgattggtatgtgcaaggttgataacatggttactgctcatggtgctgatcat 300 agaagattgagaggtttgttgtctagatctttcccaccatctagaattgctttgttggct 360 ccaagaattgaacaatgggttgatagattattggccgaaatggctcaaagaggtggttct 420 gctgatttgatgtgtgaatttgctgttccattgcctaccaatgttattgctgaattattc 480 ggtttgccagacgaacagagagaagaaatagttgctttgacttactctttggctaacact 540 tctgctactgctgctgaagttagacaaaccagacaaagaattccagagttcttcagaaga 600 ttgatcgctttgaaaaggggtcaattgggtgatgatttggcttctgctttgatagttgct 660 agagataacggtgaattggtttccgataccgaattgatcgatatgttgttcatggttttg 720 tccgctggtttcgttactactactggtgttattggtaatggtgttttggctttgttgacc 780 catccacaacaattgcatttggttagagctggtcaagttccatggtcacaagctattgaa 840 gaaattttgagatggggttcctctgttgctaatttgccttttagatacgctaccgaagat 900 gttgaaattgatggttgcatggttagaagaggtgatgctgttttgatggcttttcatgct 960 gctaatagagatgagaaagcttttggtccaggtgctgatagatttgatgttactagaagg 1020 cataacccacacttgtcttttggtgaaggtccacatttttgtttgggtgctgctttggct 1080 agattggaattgagatgtgcttttccagctttgtttgccagattggaagatttggctttg 1140 actattgctgctgaagatgttgtttacatgccatcctacgttattagatgcccacaaaga 1200 ttgccagttactttcagaccatctattgcctga 1233 SEQIDNO:54 MRVENHNRDVIGVSVAPTHLDNLSSAILQQGGMARVSLPGDVVTWAAGGHQTLRRILSDQ 60 RFNRDWRQWRALQDGEIPEDHPLIGMCKVDNMVTAHGADHRRLRGLLSRSFPPSRIALLA 120 PRIEQWVDRLLAEMAQRGGSADLMCEFAVPLPTNVIAELFGLPDEQREEIVALTYSLANT 180 SATAAEVRQTRQRIPEFFRRLIALKRGQLGDDLASALIVARDNGELVSDTELIDMLFMVL 240 SAGFVTTTGVIGNGVLALLTHPQQLHLVRAGQVPWSQAIEEILRWGSSVANLPFRYATED 300 VEIDGCMVRRGDAVLMAFHAANRDEKAFGPGADRFDVTRRHNPHLSFGEGPHFCLGAALA 360 RLELRCAFPALFARLEDLALTIAAEDVVYMPSYVIRCPQRLPVTFRPSIA 410 SEQIDNO:55 atgggtttggcttcttcttgggtcttgtacactgctatttttgctggtgctttggctttg 60 agatgggttttgttgagagttaacaagtgggtttacgagggtagattgaagggtaaatct 120 tatcatttgccaccaggtgatttgggttggccattgattggtaatatgtggacttttttg 180 agagccttcaagaccaagaatccagactctttcatttccaacatcgtcgaaagatatggt 240 aagggtggtatctacaagactttcatgtttggtaacccatccatcttggttacttctcca 300 gaaggttgtagaaaggttttgaccgatgatgataatttcaaaccaggttggccaacttct 360 accgaagaattgataggtaagaagtccttcgtcagcatctcttacgaagaacataagaga 420 ttgagaagattgacctctgctccagttaatggtcatgaagctttgtccttgtacatccct 480 tacatcgaaaagaacgttatctccgatttggagaagtggtctaagatgggtaacattgaa 540 ttcttgaccggtgttagaaagttgaccttcaagatcatcatgtacattttcttgtccgcc 600 gaatctggtgatgttatggaagctttggaaaaagagtacaccatcttgaactatggtgtt 660 agagctttggccattaacattccaggttttgcttttcataaggccttcaaggctagaaag 720 aatttggttgctactttacaagctaccgttgacgaaagaaggcaaagagaaagagaaaac 780 tcttccgctagagaaaaggatatgttggatgctttgttgcacgttgaagatgagaatggt 840 agaaaattgaccgacgaagaaatcatcgacttgttgatcatgtacttgaacgctggtcat 900 gaatcttcaggtcatgttactatgtgggctactttgttgttgcaaggtcatccagaaatt 960 ttccaaagagctaaggctgaacaagaagagatcgttaagaatagaccaccaactcaaaag 1020 ggtttgaccttgagagaagttaggaagatggaatacttgtcccaagttattgacgaaacc 1080 ttgagatggttgaccttctcattgatggttttcagagaagctaaggccgatgttaatatt 1140 ggtggttacttgtttccaaagggttggaaagttttggtttggttcagagctgttcattac 1200 gatccagaaatctacccaaatccagaagttttcaatccatccagatgggataatttcact 1260 ccaaaggctggtacttttttgccatttggtgctggttctagattgtgtccaggtaatgat 1320 ttggccaagttggaaatctctatcttcttgcactacttcttgttgaactacagattggaa 1380 agggttaacccaggttgtgaattgatgtatttgccacatccaagaccagttgataactgt 1440 ttggctagagttagaaaggttgcctga 1467 SEQIDNO:56 MGLASSWVLYTAIFAGALALRWVLLRVNKWVYEGRLKGKSYHLPPGDLGWPLIGNMWTFL 60 RAFKTKNPDSFISNIVERYGKGGIYKTFMFGNPSILVTSPEGCRKVLTDDDNFKPGWPTS 120 TEELIGKKSFVSISYEEHKRLRRLTSAPVNGHEALSLYIPYIEKNVISDLEKWSKMGNIE 180 FLTGVRKLTFKIIMYIFLSAESGDVMEALEKEYTILNYGVRALAINIPGFAFHKAFKARK 240 NLVATLQATVDERRQRERENSSAREKDMLDALLHVEDENGRKLTDEEIIDLLIMYLNAGH 300 ESSGHVTMWATLLLQGHPEIFQRAKAEQEEIVKNRPPTQKGLTLREVRKMEYLSQVIDET 360 LRWLTFSLMVFREAKADVNIGGYLFPKGWKVLVWFRAVHYDPEIYPNPEVFNPSRWDNFT 420 PKAGTFLPFGAGSRLCPGNDLAKLEISIFLHYFLLNYRLERVNPGCELMYLPHPRPVDNC 480 LARVRKVA 488 SEQIDNO:57 atgatcttggagatgggttctatgtgggttgttttgatggctattggtggtgctttgttg 60 gttttgagatccatcttgaagaatgtcaactggtggttgtacgaatctaagttgggtgtt 120 aagcaatactctttgccaccaggtgatatgggttggccttttattggtaatatgtggtct 180 ttcttgagggccttcaaatctaaagatccagactccttcatctcctccatcgtttctaga 240 tatggttcttctggtatctacaaggctttgatgtttggtaacccatctgttatcgttact 300 actccagaaggttgtaagagggttttgactgatgacgaaaagtttactactggttggcca 360 caatctaccattgaattgattggtaagaactccttcattgccatgacttacgaagaacac 420 aagagattgagaaggttgacctcctcttctattaacggtatggaagctttgtccttgtac 480 ttgaagtacatcgaagagaacgtgatcatctctttggaaaagtggtctaacatgggtcag 540 attgaattcttgaccgagattaggaagttgaccttcaagatcatcatgcacattttcttg 600 tcctccgaatctgaaccagttatggaagccttggaaaaagagtacaccattttgaaccat 660 ggtgttagagctatgcaaatcaatgttccaggtttcgcttactacaaagctttgaaggct 720 agaaagaacttggtcggtattttccaatccatcgttgatgacagaagaaacatcagaaag 780 gtctactcccaaaaaaaggccaaggatatgatggattccttgatcgatgttgaagatgac 840 aacggtagaaagttgaacgacgaagatatcatcgacatcatgttgatgtacttgaacgct 900 ggtcatgaatcctctggtcatattactatgtgggctacttacttcttgcaaaagcaccca 960 gaatacttgaagaaggccaaagaagaacaagaagaaatcatcaagagaaggccatctact 1020 caaaagggtttgaccttgaaagaaatcagaggtatggacttcttgtacaaggttattgac 1080 gaaaccatgagggtgattaccttctcattggttgttttcagagaagccaagtctgatgtt 1140 accattaacggttacactattccaaagggttggaaggttttgacctggtttagatctgtt 1200 catttggacccagaaatctacccaaacccaaaagaattcaacccaaacaggtggaacaaa 1260 gaacataaggctggtgaatttttgccatttggtgctggtactagattgtgtccaggtaat 1320 gatttggccaagatggaaattgctgttttcttgcatcatttcaccttgaactacaggttg 1380 gaacaattgaatccaaagtgcccaattagatacttgccacatacaagaccaatggataac 1440 tgtttgggtagagttaagaagtgttaa 1467 SEQIDNO:58 MILEMGSMWVVLMAIGGALLVLRSILKNVNWWLYESKLGVKQYSLPPGDMGWPFIGNMWS 60 FLRAFKSKDPDSFISSIVSRYGSSGIYKALMFGNPSVIVTTPEGCKRVLTDDEKFTTGWP 120 QSTIELIGKNSFIAMTYEEHKRLRRLTSSSINGMEALSLYLKYIEENVIISLEKWSNMGQ 180 IEFLTEIRKLTFKIIMHIFLSSESEPVMEALEKEYTILNHGVRAMQINVPGFAYYKALKA 240 RKNLVGIFQSIVDDRRNIRKVYSQKKAKDMMDSLIDVEDDNGRKLNDEDIIDIMLMYLNA 300 GHESSGHITMWATYFLQKHPEYLKKAKEEQEEIIKRRPSTQKGLTLKEIRGMDFLYKVID 360 ETMRVITFSLVVFREAKSDVTINGYTIPKGWKVLTWFRSVHLDPEIYPNPKEFNPNRWNK 420 EHKAGEFLPFGAGTRLCPGNDLAKMEIAVFLHHFTLNYRLEQLNPKCPIRYLPHTRPMDN 480 CLGRVKKC 488 SEQIDNO:59 atgactgaaaccggtttgatcttgatgtggttcccattgattatcttgggtttgttcgtt 60 ttgaagtgggttttgaagagagttaacgtctggatctacgtttctaagttgggtgaaaaa 120 aagcactatttgccaccaggtgatttgggttggccagttattggtaatatgtggtctttt 180 ttgagagccttcaagacctctgatccagaatctttcattcagtcctacattaccagatac 240 ggtagaactggtatctacaaggctcatatgtttggttacccatgtgttttggttactact 300 ccagaaacctgtagaagagttttgactgatgatgatgccttccatattggttggccaaaa 360 tctaccatgaagttgatcggtagaaagtccttcgttggtatctctttcgaagaacacaag 420 agattgagaagattgacttctgctccagttaatggtccagaagctttgtctgtttacatc 480 cagttcattgaagaaaccgttaacaccgatttggagaagtggtctaaaatgggtgaaatc 540 gaattcttgtcccacttgagaaagttgaccttcaaggttattatgtacatcttcttgtcc 600 tccgaatccgaacatgttatggattctttggaaagagagtacaccaacttgaactatggt 660 gttagagctatgggtattaacttgccaggttttgcttatcatagagctttgaaggctaga 720 aagaaattggttgctgctttccaatctatcgtcaccaacagaagaaatcagagaaagcag 780 aacatctcctccaacagaaaagatatgttggacaacttgatcgacgtcaaggacgaaaat 840 ggtagagttttggatgacgaagaaatcatcgacttgttgttgatgtacttgaacgctggt 900 catgaatcttcaggtcatttgactatgtgggctaccattttgatgcaagaacatccaatg 960 atcttgcagaaggccaaagaagaacaagaaagaatcgttaagaaaagagccccaggtcaa 1020 aagttgactttgaaagaaactagggaaatggtctacttgtcccaagttattgacgaaacc 1080 ttgagagtgattaccttctcattgactgctttcagagaagccaaatccgatgttcaaatg 1140 gatggttacattatcccaaagggttggaaagttttgacgtggtttagaaacgttcacttg 1200 gatccagaaatctacccagatccaaaaaagttcgatccatcaagatgggaaggttacact 1260 ccaaaagctggtacttttttgccatttggtttgggttctcatttgtgtccaggtaatgat 1320 ttggccaagttggaaatctccatcttcttgcatcatttcttgttgaagtacagggtcgaa 1380 agatctaatccaggttgtccagttatgttcttgccacataatagaccaaaggataactgc 1440 ttggctagaattactagaaccatgccatga 1470 SEQIDNO:60 MTETGLILMWFPLIILGLFVLKWVLKRVNVWIYVSKLGEKKHYLPPGDLGWPVIGNMWSF 60 LRAFKTSDPESFIQSYITRYGRTGIYKAHMFGYPCVLVTTPETCRRVLTDDDAFHIGWPK 120 STMKLIGRKSFVGISFEEHKRLRRLTSAPVNGPEALSVYIQFIEETVNTDLEKWSKMGEI 180 EFLSHLRKLTFKVIMYIFLSSESEHVMDSLEREYTNLNYGVRAMGINLPGFAYHRALKAR 240 KKLVAAFQSIVTNRRNQRKQNISSNRKDMLDNLIDVKDENGRVLDDEEIIDLLLMYLNAG 300 HESSGHLTMWATILMQEHPMILQKAKEEQERIVKKRAPGQKLTLKETREMVYLSQVIDET 360 LRVITFSLTAFREAKSDVQMDGYIIPKGWKVLTWFRNVHLDPEIYPDPKKFDPSRWEGYT 420 PKAGTFLPFGLGSHLCPGNDLAKLEISIFLHHFLLKYRVERSNPGCPVMFLPHNRPKDNC 480 LARITRTMP 489 SEQIDNO:61 atggctgaaactacttcttggattccagtttggtttccattgatggttttgggttgtttt 60 ggtttgaactggttggttagaaaggttaacgtttggttgtacgaatcttccttgggtgaa 120 aacagacattatttgccaccaggtgatttgggttggccttttattggtaatatgttgtcc 180 ttcttgagagccttcaaaacctctgatccagattctttcactaggaccttgattaagaga 240 tacggtccaaaaggtatctacaaggctcatatgtttggtaacccatctattatcgttacc 300 acctctgatacctgtagaagagttttgactgatgatgatgcttttaaaccaggttggcca 360 acttctaccatggaattgattggtagaaagtccttcgttggtatctctttcgaagaacac 420 aagagattgagaagattgactgctgctccagttaatggtcatgaagctttgtctacctac 480 atcccttacatcgaagaaaacgttattaccgttttggacaagtggactaagatgggtgaa 540 tttgaattcttgacccacttgagaaagttgaccttcagaatcatcatgtacattttcttg 600 tcctccgaatccgaaaacgttatggatgctttggaaagagagtacactgctttgaattat 660 ggtgttagagctatggccgttaacattccaggttttgcttatcatagagctttgaaggct 720 agaaagactttggttgctgctttccaatctatcgttaccgaaagaagaaatcagaggaag 780 cagaacatcttgtccaacaaaaaggatatgttggacaacttgttgaacgttaaggacgaa 840 gatggtaagaccttggatgatgaagaaatcatcgatgtcttgttgatgtacttgaacgct 900 ggtcatgaatcttccggtcatacaattatgtgggctactgttttcttacaagaacaccca 960 gaagttctacaaagagctaaagctgaacaagaaatgatcttgaagtctagaccagaaggt 1020 caaaagggcttgtctttgaaagaaaccagaaagatggaattcttgtcccaagttgttgac 1080 gaaaccttgagagttattaccttctcattgaccgctttcagagaagctaaaaccgatgtt 1140 gaaatgaacggttacttgattccaaagggttggaaagttttgacgtggttcagagatgtt 1200 catatcgatccagaagttttcccagatccaagaaaatttgatccagctagatgggataat 1260 ggtttcgttccaaaagctggtgcttttttgccatttggtgctggttctcatttgtgtcca 1320 ggtaatgatttggccaagttggaaatctccatcttcttgcatcactttttgttgaagtac 1380 caggtcaagagatctaacccagaatgtccagttatgtacttgccacatacaagaccaact 1440 gataactgcttggctagaatctcttaccagtga 1473 SEQIDNO:62 MAETTSWIPVWFPLMVLGCFGLNWLVRKVNVWLYESSLGENRHYLPPGDLGWPFIGNMLS 60 FLRAFKTSDPDSFTRTLIKRYGPKGIYKAHMFGNPSIIVTTSDTCRRVLTDDDAFKPGWP 120 TSTMELIGRKSFVGISFEEHKRLRRLTAAPVNGHEALSTYIPYIEENVITVLDKWTKMGE 180 FEFLTHLRKLTFRIIMYIFLSSESENVMDALEREYTALNYGVRAMAVNIPGFAYHRALKA 240 RKTLVAAFQSIVTERRNQRKQNILSNKKDMLDNLLNVKDEDGKTLDDEEIIDVLLMYLNA 300 GHESSGHTIMWATVFLQEHPEVLQRAKAEQEMILKSRPEGQKGLSLKETRKMEFLSQVVD 360 ETLRVITFSLTAFREAKTDVEMNGYLIPKGWKVLTWFRDVHIDPEVFPDPRKFDPARWDN 420 GFVPKAGAFLPFGAGSHLCPGNDLAKLEISIFLHHFLLKYQVKRSNPECPVMYLPHTRPT 480 DNCLARISYQ 490 SEQIDNO:63 atggcttccttgtggtttattttcggtgctattgctggtgctttgttggttttgagatct 60 ttgttgaagaacgtcaactggttcttgtacgaagctaaattgggtgacaagcaatattct 120 ttgccaccaggtgatatgggttggccaattattggtaatatgtggtctttcttgagggcc 180 ttcaaatcttctaagccagattctttcatggactccatcgttaagagatttggtaacact 240 ggtatctacaaggtgttcatgtttggtttcccatctgttatcgttacttctccagaagct 300 tgcaaaaaggttttgactgatgacgaaaatttcgaaccaggttggccacaatctaccgtt 360 gaattgattggtgaaaagtccttcatcaagatgccattcgaagaacatagaaggttgaga 420 agattgacctccgcttctattaacggttatgaagctttgtccgtctacttgaagtacatc 480 gaagaaatcgtcatctcctcattggaaaagtggactcaaatgggtgaaatcgaattcttg 540 acccagatgagaaagttgaccttcaagatcatcatccacattttcttgggttccgaatct 600 gaaccagttatggaagctttggaaagagagtacactgttttgaacttgggtgttagagct 660 atgagaatcaacattccaggtttcgctttccacaaatctttgaaggctagaaagaacttg 720 gttgccatcttccaatctatcgttgacaagagaagaaacgagagaagaggtaaagaacca 780 gctccaggtaaaaaagctaaggatatgatggattccttgatcgatgctgttgacgaaaat 840 ggtagaaaattgggtgatgacgaaatcatcgacatcatgttgatgtacttgaacgctggt 900 catgaatcctctggtcatattactatgtgggctacttacttcttgcaaagacatccagaa 960 ttcttcagaaaggccaaagaagaacaagtcgagatgttgaaaagaaggccaccatctcaa 1020 aaaggtttgaagttggaagatgtgagaaagatggaatacttgtccaaggttattgacgaa 1080 accatgagagttgttaccttcagcttgatggttttcagacaagctagaaacgatgttaag 1140 gtcaacggttacttgattccaaaaggttggagagttttgacgtggttcagatctgttcat 1200 ttcgattccgaattatacccagacccaagagaattcaatccagaaaacttctccgttgtt 1260 agaaaggctggtgaatttttgccatttggtgctggtactagattgtgtccaggtaatgat 1320 ttggccaagttggaaatctctgttttcttgcatcacttcttgttgaagtacgaattggaa 1380 cagttgaacccaaagtccccaattagatttttgccacatacaagaccattggataactgc 1440 ttggctagaatcaaaaaacaagaagctgcctaa 1473 SEQIDNO:64 MASLWFIFGAIAGALLVLRSLLKNVNWFLYEAKLGDKQYSLPPGDMGWPIIGNMWSFLRA 60 FKSSKPDSFMDSIVKRFGNTGIYKVFMFGFPSVIVTSPEACKKVLTDDENFEPGWPQSTV 120 ELIGEKSFIKMPFEEHRRLRRLTSASINGYEALSVYLKYIEEIVISSLEKWTQMGEIEFL 180 TQMRKLTFKIIIHIFLGSESEPVMEALEREYTVLNLGVRAMRINIPGFAFHKSLKARKNL 240 VAIFQSIVDKRRNERRGKEPAPGKKAKDMMDSLIDAVDENGRKLGDDEIIDIMLMYLNAG 300 HESSGHITMWATYFLQRHPEFFRKAKEEQVEMLKRRPPSQKGLKLEDVRKMEYLSKVIDE 360 TMRVVIFSLMVFRQARNDVKVNGYLIPKGWRVLTWFRSVHFDSELYPDPREFNPENFSVV 420 RKAGEFLPFGAGTRLCPGNDLAKLEISVFLHHFLLKYELEQLNPKSPIRFLPHTRPLDNC 480 LARIKKQEAA 490 SEQIDNO:65 atggaatctacttgggctgttgctgctgttgttacagctgttgttgcagttgctactgtt 60 ttctctgttttgaaatgggctgctaagtctttgaacgaatggatctatgaagctaagttg 120 ggtgatagaagattggctttgccaccaggtgatttgggttggccattgattggtaatatg 180 ttgggttttttgagggccttcaagtctaagaatccagaaactttcatcgacggttacgtt 240 tctagatacggtaaaactggtgtttacaaggttcacttgtttggtaacccatctgttgtt 300 gttactactccagaaacctgtagaaaggttttgactgatgatgaagcttttcaaccaggt 360 tggccaagagctgctgttgaattgattggtgaaaagtccttcatccagatgccacaagaa 420 gaacataagagattgagaagattgacctctgctccagttaatggttttgaagctttgtcc 480 aactacatcccttacatcgaaaagaacgtcttggaatctttggagaagtggtctaaaatg 540 ggtccaattgaattcttgacccagttgagaaagttgaccttcaccgttattatgtacatc 600 ttcttgtcctccgaatccgaaccagttatggaaatgttggaaaaagagtacaccaggttg 660 aactacggtgttagagatatgagaatcaacttgccaggtttcgcttatcataaggctttg 720 aaggctagaaagaatttggttgctgctttgaagggtatcgttactgaaagaagaaggcaa 780 aagttggataagtgggctccaaaaagaaaggatatgatggaccaattgatcgacatcgtt 840 gacgaaaatggtagaaagttggatgacgaagaaatcatcgacatcttgatcatgtacttg 900 aacgctggtcatgaatcttcaggtcatacaatgatgtgggctaccatcttgttgaatcaa 960 catccagaagttttgaagaaggccagggaagaacaagaagctatcgttagaaatagacca 1020 gcaggtcaaactggcttgactttgaaagaatgtagagacatggaatacttgtccaaggtt 1080 gttgacgaaaccttgagatacgtttccttctcattggtcgttttcagagaagctcaaatg 1140 gatgttaacttgaacggttacttgattccaaagggttggaaagttttggcctggttcaga 1200 tctattcactacgattctgaagtttacccagacccaaaaaagttcgaaccatcaagatgg 1260 gatggttttgttccaaaagctggtgaatttttgccatttggtgctggttctagattgtgt 1320 ccaggtaatgatttggctaagttggaaatctgcatcttcgtccactactttttgttgaac 1380 tacaacttggaatggttgaccccagattgtgaaatcttgtatttgccacattccagacca 1440 aaggataactgcatggctaagattaccaagaaatcttctgttgctgcctaa 1491 SEQIDNO:66 MESTWAVAAVVTAVVAVATVFSVLKWAAKSLNEWIYEAKLGDRRLALPPGDLGWPLIGNM 60 LGFLRAFKSKNPETFIDGYVSRYGKTGVYKVHLFGNPSVVVTTPETCRKVLTDDEAFQPG 120 WPRAAVELIGEKSFIQMPQEEHKRLRRLTSAPVNGFEALSNYIPYIEKNVLESLEKWSKM 180 GPIEFLTQLRKLTFTVIMYIFLSSESEPVMEMLEKEYTRLNYGVRDMRINLPGFAYHKAL 240 KARKNLVAALKGIVTERRRQKLDKWAPKRKDMMDQLIDIVDENGRKLDDEEIIDILIMYL 300 NAGHESSGHTMMWATILLNQHPEVLKKAREEQEAIVRNRPAGQTGLTLKECRDMEYLSKV 360 VDETLRYVSFSLVVFREAQMDVNLNGYLIPKGWKVLAWFRSIHYDSEVYPDPKKFEPSRW 420 DGFVPKAGEFLPFGAGSRLCPGNDLAKLEICIFVHYFLLNYNLEWLTPDCEILYLPHSRP 480 KDNCMAKITKKSSVAA 496 SEQIDNO:67 atgggtgaaggtgcttggtgggctgttgctgctgttgttgctgctttggctgttgttgca 60 ttggatgctgctgttagaactgctcatgcttggtattggactgcttctttgggtgctggt 120 agaagaggtagattgccaccaggtgatatgggttggccattggttggtggtatgtgggct 180 tttttgagagcttttaaatctggtagaccagactccttcattgattcttttgctagaaga 240 tttggtagagccggcttgtatagagcttttatgttttcttctccaaccattatggctact 300 actccagaagcttgtaagcaagttttgatggatgatgatgctttcgttactggttggcca 360 aaagctactgttgctttgattggtccaaagtcctttgttaacatgggttacgatgaacac 420 agaaggttgagaaaattgactgctgctccaatcaatggtttcgatgctttgacttcttac 480 ttgggtttcatcgatgatactgttgttactactttgaggggttggtctgaaaggggtggt 540 gatggtcattttgaattcttgactgaattgagaaggatgaccttcagaatcatcgtccaa 600 attttcatgggtggtgctgacgaaagaactgctgctgaattggaaagaacttacaccgaa 660 ttgaactacggtatgagagctatggctattgatttgccaggttttgcttaccataaggct 720 attagagctagaagaagattggttgctgctttacaaagagttttggacgagagaagggct 780 agaggtggtaaaactgctgctggtgctgctgctccagttgatatgatggatagattgatt 840 gccgttgaagatgaaggtggtagaagattgcaagatgacgaaatcatcgatgtcttggtc 900 atgtatttgaacgctggtcatgaatcctctggtcatattactatgtgggctactgttttc 960 ttgcaagagaacccagaaattttggctaaagctaaagctgaacaagaggccattatgaga 1020 tctattccaccaggtcaaaaaggcttgactttgagagattttagaaagatggcctacttg 1080 tcccaagttgttgacgaaactttgagattcgtcaacatctccttcgtgtcttttagacaa 1140 gctaccagagatgttttcgtcaacggttacttgattccaaaaggttggaaagtccaattg 1200 tggtacagatccgttcatatggatccacaagtttatccagatccaaagaagttcgatcca 1260 tcaagatgggaaggtccaccaccaagagctggtacttttttgccatttggtttgggtact 1320 agattgtgtccaggtaatgatttggccaagttggaaatctcagttttcttgcatcatttc 1380 ttgttgggctacaagttgactagaaagaacccaaactgtagagtcagatatttgccacat 1440 ccaagaccagttgataactgcttggctaagattaccagattgtcatcttctcacggttaa 150 SEQIDNO:68 MGEGAWWAVAAVVAALAVVALDAAVRTAHAWYWTASLGAGRRGRLPPGDMGWPLVGGMWA 60 FLRAFKSGRPDSFIDSFARRFGRAGLYRAFMFSSPTIMATTPEACKQVLMDDDAFVTGWP 120 KATVALIGPKSFVNMGYDEHRRLRKLTAAPINGFDALTSYLGFIDDTVVTTLRGWSERGG 180 DGHFEFLTELRRMTFRIIVQIFMGGADERTAAELERTYTELNYGMRAMAIDLPGFAYHKA 240 IRARRRLVAALQRVLDERRARGGKTAAGAAAPVDMMDRLIAVEDEGGRRLQDDEIIDVLV 300 MYLNAGHESSGHITMWATVFLQENPEILAKAKAEQEAIMRSIPPGQKGLTLRDFRKMAYL 360 SQVVDETLRFVNISFVSFRQATRDVFVNGYLIPKGWKVQLWYRSVHMDPQVYPDPKKFDP 420 SRWEGPPPRAGTFLPFGLGTRLCPGNDLAKLEISVFLHHFLLGYKLTRKNPNCRVRYLPH 480 PRPVDNCLAKITRLSSSHG 499 SEQIDNO:69 atgccacaagctattccagctcataagatgatgccaattccaggtgttggtgtttacgtt 60 tttactgttttgtgggctgctactatctacattgcttcatctttgttgagatggtccttg 120 gattccttgaaacatttgccaatcgtcaacaacaaagaatggtactctttgtctggtaga 180 aaggccaagttgagatttttggctgaatccaagtctttgttggaagaagctagaaagaga 240 tacccacaacaaccattcagaatcttgtctaattggggtgttttgttggttttgccatct 300 tgttttgccgacgaaatcagaaacgatcagagattgtctttttcaaaggctgccttgcaa 360 gattcccatggtcatattccaggtttggaaactgttaagttggttgccagagatgaccaa 420 ttgattcaaaccgttgctagaaagcacttgaccaaacatttggccaaagttatccaacca 480 ttgtccgaagaaactgaattcgctttggatcaaaacttcggtcataacccagccatcttg 540 gatattattgccagaatctcttccaggatctacttgggtgatgaattgtgtagaaatact 600 gcttggttggctactactaaggtttacacttctgctttttttgctgccccagttaagttg 660 ggtttgattccagctccattgagaagattggctcattggttgattccagaatgcaagatc 720 ttgagagaacaagttcaagaagccagaagaatcatcgaaccattggttagaagaaggcaa 780 gctttgagagctaaagctttggctgaaggttgtccaactccacaattcaatgatgctttg 840 ggttgggctgctgaagaatctgctaaaaatggtaaagattacgatccagccattacccaa 900 ttggctttgtctatgttggctattcataccacctacgacttgttccaacaatgcatttta 960 gatttggcccaaaacccacatttcatcgaacctttgagacaagaagccatcgaagtcatt 1020 caacaatatggttggacaaagcaaggcttgtaccatatgaagttgttggattccgctttg 1080 aaagaaacccaaagattgaaaccaggttccatggttactatgagaagatatgtcttggag 1140 gacttgcaattgtccaacggtttgattttgaaaaagggcaccagaatcaacatcgacact 1200 caaagaatgagagatccagacttgcatgaagatccattgaagtacgatgctttcaggttc 1260 tacaagatgagacaacaaccaggtggtgaacatactgctcaattggtttctacttctcca 1320 gatcatttgggttttggtcatggtgaacattcttgtccaggtagattttttgctgctaac 1380 gaaatcaaagttgccatggctcatatgttgatcaagtacgaatggaaaccagctggtcat 1440 tcttctgctggtccagatgttaagggtttgttgatgaagtctggtgctggtgctcaaatt 1500 gatatcagaagaagagaaaccgttgagatcgcttga 1536 SEQIDNO:70 MPQAIPAHKMMPIPGVGVYVFTVLWAATIYIASSLLRWSLDSLKHLPIVNNKEWYSLSGR 60 KAKLRFLAESKSLLEEARKRYPQQPFRILSNWGVLLVLPSCFADEIRNDQRLSFSKAALQ 120 DSHGHIPGLETVKLVARDDQLIQTVARKHLTKHLAKVIQPLSEETEFALDQNFGHNPAIL 180 DIIARISSRIYLGDELCRNTAWLATTKVYTSAFFAAPVKLGLIPAPLRRLAHWLIPECKI 240 LREQVQEARRIIEPLVRRRQALRAKALAEGCPTPQFNDALGWAAEESAKNGKDYDPAITQ 300 LALSMLAIHTTYDLFQQCILDLAQNPHFIEPLRQEAIEVIQQYGWTKQGLYHMKLLDSAL 360 KETQRLKPGSMVTMRRYVLEDLQLSNGLILKKGTRINIDTQRMRDPDLHEDPLKYDAFRF 420 YKMRQQPGGEHTAQLVSTSPDHLGFGHGEHSCPGRFFAANEIKVAMAHMLIKYEWKPAGH 480 SSAAGPDVKLLMKSGAGAQIDIRRRETVEIA 511 SEQIDNO:71 atggaagtcggtatggttatgaaggcttctttgtctttgtgttgtgttggtgcttgttgt 60 ttggccttgtacttgtattatatcgtttgggttgttccacaaaggttgttggctggtttt 120 agaaggcaaggtattggtggtccaagaccatcttttccatatggtaatttggccgatatg 180 aaggaagctgttgctgctgctaaagttgcttctagaggtgttggtggtatcgttcatgat 240 tatagaccagctgttttgccattctacgagaagtggagaaaagaacatggtccagttttc 300 acttactccatgggtaatgttgttttcttgcacgtttctagaccagatgttgttagagat 360 atcaacttgtgcgtttccttggacttgggtaaatcttcttacttgaaggctactcacgaa 420 cctttgtttggtagaggtattttgaagtctaatggtcaagcttgggctcaccaaagaaag 480 attattgctccagcattcttcttggataaggttaagggtatggttgatttgatggttgat 540 tctgctcaaaccttgttgaagtcttgggaagaaagggttgatggtaatggtggtactgtt 600 aacatcaagatcgatgatgatatcagagcttactccgccgatgttatttctagaacttgt 660 ttcggttcctcctacatcaagggtaagaagatctttttgaagttgagagaattgcagaag 720 gccgtttctaagccaaatgttttggctgaaatgactggtttgaggttgtttccaactaag 780 aagaatagacaagcctgggaattgcatagacaagttcataagttgatcttggaaatcgtc 840 aaagaatccggtgaggataagaacttgttgtctactattttacactccgcctcttcatct 900 aaagttggtttgggtgaagctgaaaacttcatcgttgataactgcaagtctatctacttc 960 gctggttatgaatctactgctgttactgctgcttggtgtttgatgttgttgggtttacat 1020 ccagaatggcaagataaggttagagaagaggttcaagaggtttgtggtggtagaccaatt 1080 gattctcaatccttgcaaaagatgaagaacctaaccatggtcatccaagaaactttgaga 1140 ttatatccagctggtgccttcgtttctagaatggctttacaagaattgaagttgggtggt 1200 gttaacatcccaaagggtgttaatatctacatcccagtttctaccatgcacttggatcca 1260 aaattgtggggtgctgatgtcaaagaattcaacccagaaagattctctgatgccagacca 1320 caattgcattcttatttgccatttggtgctggtgctagaacatgtttgggtcaaggtttt 1380 gctactgccgaattgaagattttgatctccttgatcatttccaagttcgccttgaagttg 1440 tccccattatatgaacattctccaaccttgaagttggtcgttgaaccagaatttggtgtt 1500 gatttgactttgaccaaagttcaaggtgcttgtagatgctga 1542 SEQIDNO:72 MEVGMVMKASLSLCCVGACCLALYLYYIVWVVPQRLLAGFRRQGIGGPRPSFPYGNLADM 60 KEAVAAAKVASRGVGGIVHDYRPAVLPFYEKWRKEHGPVFTYSMGNVVFLHVSRPDVVRD 120 INLCVSLDLGKSSYLKATHEPLFGRGILKSNGQAWAHQRKIIAPAFFLDKVKGMVDLMVD 180 SAQTLLKSWEERVDGNGGTVNIKIDDDIRAYSADVISRTCFGSSYIKGKKIFLKLRELQK 240 AVSKPNVLAEMTGLRLFPTKKNRQAWELHRQVHKLILEIVKESGEDKNLLSTILHSASSS 300 KVGLGEAENFIVDNCKSIYFAGYESTAVTAAWCLMLLGLHPEWQDKVREEVQEVCGGRPI 360 DSQSLQKMKNLTMVIQETLRLYPAGAFVSRMALQELKLGGVNIPKGVNIYIPVSTMHLDP 420 KLWGADVKEFNPERFSDARPQLHSYLPFGAGARTCLGQGFATAELKILISLIISKFALKL 480 SPLYEHSPTLKLVVEPEFGVDLTLTKVQGACRC 513 SEQIDNO:73 atggctttcactgctcaatcctacttcgatattggtgaacacttgagagtttccgtcatt 60 ttgttgttgactaccgttgttttgttgttggtgttctctttgaaggccagaaagaaatct 120 ttgttgccattggttaatggtaacagatggactgatccattgggtattgaagccaagaaa 180 aagttcatgacctccgccagatctattattgctgaacaattggaaaaagccccaggtaaa 240 cctttcagagttgtttctgatgttggtgaattggttgttttgccaccagaatttgctcca 300 gaaatcagaaaccacaaggacttttcttttaccatggctgcttacaagtggttctatgct 360 catttgccaggtatggaaggttttagagaaggtactaccgaatcccaaatcatgaagttg 420 gttgctagacatcaattgactcaccaattgactgttgttactgctccagttgctgaagaa 480 tctgctagagctttgagagatgttttcggttgtgatgaaggttggagagaattgggtact 540 agacaagcttgcttgcaagttattgctagagtctcctctagaatcttcttgggtcaagaa 600 ttgtgtagaaacccagattggttgagagttacttctacctattctgttttggctttcaga 660 gccgttgttgttttgagattttggccagctccattgagaaatttggttcattggtttttg 720 ccagcttgtaaggctgctagagatttggttcaagaagctagagacttggttaaccctttg 780 ttgcaagaaagaaacgaagaaagaagggctcaagctaaaggtgaatctgtcttgtataga 840 aacgatgccattgactggttggaagaattagctactgataagaacttgaactacgatcca 900 gctgcttctcaattgtctttgtctactgctgctttacactcttctactgattttttcgct 960 cagttgttgttggatttggctgaaagaccaggtttggctgaagaattgagacaagaagct 1020 gctaaggttgttaatactgaaggttggtctaagggttccttgttcgatttgaaattgatg 1080 gactccgtcatgaaggaatcccaaagattgaaacctatttccttggcctctatgagaaga 1140 tacactactgctgatgttaagatgtcctccggtgatgttattccaaaaggttctttgaca 1200 gttgtctccgcttatagacattgggacgaaaaaacttacgaaaggccagatgaattcgat 1260 ggtcatagattcttgaggatgagatcccaagaaggtaaagaacatcaagcccatttggtt 1320 tctgctacccaagatcattttggtttcggttatggtttacatgcttgtccaggtagattt 1380 ttcgctgctgaagaagttaagatcgttttggctcaaatgttgttgcagtacgaaattaga 1440 ttggttgccggttctgattctagaccagttcatgctggtttgaatatgtatgctaatcca 1500 gcctccaagatctccgttagatatagaggttcttccttttaa 1542 SEQIDNO:74 MAFTAQSYFDIGEHLRVSVILLLTTVVLLLVFSLKARKKSLLPLVNGNRWTDPLGIEAKK 60 KFMTSARSIIAEQLEKAPGKPFRVVSDVGELVVLPPEFAPEIRNHKDFSFTMAAYKWFYA 120 HLPGMEGFREGTTESQIMKLVARHQLTHQLTVVTAPVAEESARALRDVFGCDEGWRELGT 180 RQACLQVIARVSSRIFLGQELCRNPDWLRVTSTYSVLAFRAVVVLRFWPAPLRNLVHWFL 240 PACKAARDLVQEARDLVNPLLQERNEERRAQAKGESVLYRNDAIDWLEELATDKNLNYDP 300 AASQLSLSTAALHSSTDFFAQLLLDLAERPGLAEELRQEAAKVVNTEGWSKGSLFDLKLM 360 DSVMKESQRLKPISLASMRRYTTADVKMSSGDVIPKGSLTVVSAYRHWDEKTYERPDEFD 420 GHRFLRMRSQEGKEHQAHLVSATQDHFGFGYGLHACPGRFFAAEEVKIVLAQMLLQYEIR 480 LVAGSDSRPVHAGLNMYANPASKISVRYRGSSF 513 SEQIDNO:75 atgagagttatggttgatcaagacttgtgtggtacttctggtcaatgtgttttgactttg 60 ccaggtacttttagacaaagggaaccagatggtgttgctgaagtttgtgttgctactgtt 120 ccacatgctttacatgctgctgttagattggctgcttctcaatgtccagttgctcattct 180 ggtcatagaaaaagaaggtggaggtggagagctagacaagctccaactttgagattattg 240 cagagaaggccatgtggtatgccaagaaaaacttctaccatctaa 285 SEQIDNO:76 MRVMVDQDLCGTSGQCVLTLPGTFRQREPDGVAEVCVATVPHALHAAVRLAASQCPVAHS 60 GHRKRRWRWRARQAPTLRLLQRRPCGMPRKTSTI 94 SEQIDNO:77 atgatggacatggaaatggaagttggtatggttatgaaggtcttgttgggtttgtgttgt 60 gttggtgcttgttctttggcactatacttgtattacaccgtttgggttgtcccacaaaga 120 ttattggctggttttagaaggcaaggtattggtggtccaagaccatcttttccatatggt 180 aatatggccgatatgagagaagctgttgctgctgctaaatctgctagaagatctggtggt 240 agaatgagaatcgttcatgattatagaccagccgttttgccattttacgagaagtggaga 300 aaagaacatggtccagttttcacttactccatgggtaatgttgttttcttgcacgtttct 360 agaccagatgttgttagagatatcaacttgtgcgtttccttggacttgggtaaatcttct 420 tacttgaaggctactcacgaacctttgtttggtagaggtattttgaagtctaatggtgaa 480 gcttgggctcaccaaagaaagattattgctccagaattcttcttggacaaggttaagggt 540 atggttgatttgatggttgattctgctcaaaccttgttggaatcttgggaagctagagtt 600 gataagtctggtggtactgttgatatcaagatcgatgatgatatcagagcttactccgcc 660 gatgttatttctagaacttgtttcggttcctcctacgttaagggtaagaagatctttttg 720 aagttgagagaattgcagaaggccgtttctaagccaaatgttttggctgaaatgaccggt 780 ttgagattctttccaactaagaagaatagacaagcctggggtttacacaagcaagttcat 840 agattgatcttggaaatcgtcaaagaatccggtgaggataagaatttgttgagagctatt 900 ttacactccgcctcttcatctaaagttggtttgggtgaagctgaaaacttcatcgttgat 960 aactgcaagtctatctacttcgctggttatgaatctactgctgttactgctgcttggtgt 1020 ttgatgttgttgggtttacatccagaatggcaagatagagttagacaagaggttttggaa 1080 gtttgtggtggtagaccattggattctcaatccttgcaaaagatgaagaacctaaccatg 1140 gtcatccaagaaactttgagattatatccagctggtgccttcgtttctagaatggcttta 1200 caagaattgaagttgggtggtgttcatatcccaaagggtgttaatatctacatcccagtt 1260 tctaccatgcacttggatccaaaattgtggggtccagatgctaaagaattcaatccagct 1320 agattctctgatgccagaccacaattgcattcttatttgccatttggtgctggtgctaga 1380 acatgtttgggtcaaggttttgctactgccgaattgaagattttgatctccttgatcatt 1440 tccaagttcgccttgagattgtccccattatatcaacattctccagccttgaagttgatc 1500 gttgaaccagaatttggtgttgatatcaccttgactaaggttcaaactgcttctactact 1560 acctactaa 1569 SEQIDNO:78 MMDMEMEVGMVMKVLLGLCCVGACSLALYLYYTVWVVPQRLLAGFRRQGIGGPRPSFPYG 60 NMADMREAVAAAKSARRSGGRMRIVHDYRPAVLPFYEKWRKEHGPVFTYSMGNVVFLHVS 120 RPDVVRDINLCVSLDLGKSSYLKATHEPLFGRGILKSNGEAWAHQRKIIAPEFFLDKVKG 180 MVDLMVDSAQTLLESWEARVDKSGGTVDIKIDDDIRAYSADVISRTCFGSSYVKGKKIFL 240 KLRELQKAVSKPNVLAEMTGLRFFPTKKNRQAWGLHKQVHRLILEIVKESGEDKNLLRAI 300 LHSASSSKVGLGEAENFIVDNCKSIYFAGYESTAVTAAWCLMLLGLHPEWQDRVRQEVLE 360 VCGGRPLDSQSLQKMKNLTMVIQETLRLYPAGAFVSRMALQELKLGGVHIPKGVNIYIPV 420 STMHLDPKLWGPDAKEFNPARFSDARPQLHSYLPFGAGARTCLGQGFATAELKILISLII 480 SKFALRLSPLYQHSPALKLIVEPEFGVDITLTKVQTASTTTY 522 SEQIDNO:79 atgtccatcttcaacatgattacctcttatgctggttctcagttgttgccattctacatt 60 gctatcttcgttttcactttggttccatgggctattagattctcttggttggaattgaga 120 aagggttcttttgttccattggctaatccaccagattctttgtttggtactggtaagact 180 agaaggtccttcgttaagttgtccagagaaattttggctaaggccagatctttgtttcca 240 aacgaaccattcagattgattaccgattggggtgaagttttgattttgccaccagatttt 300 gccgacgaaattagaaatgatccaagattgtctttctcaaaggctgccatgcaagataat 360 catgctggtattccaggtttcgaaactgttgctttggttggtagagaagatcagttgatt 420 caaaaggttgccagaaagcaattgaccaaacatttgtccgctgttatcgaaccattgtct 480 agagaatctactttggccgtttctttgaacttcggtgaaactactgagtggagagctatt 540 agattgaagccagccattttggatattatcgccagaatctcttccaggatctatttgggt 600 gatcaattgtgtagaaacgaagcctggttgaagattactaagacttacactaccaacttc 660 tacaccgcttctaccaatttgagaatgttcccaagatccattagaccattggctcattgg 720 tttttgccagaatgtagaaagttgagacaagaaagaaaggatgccattggtattatcacc 780 ccattgatcgaaagaagaagagaattgagaagggctgctattgctgctggtcaaccattg 840 ccagtttttcatgatgctattgactggtctgaacaagaagctgaagctgctggtactggt 900 gcttctttgtatccagttattttccagttgaccttgtccttgttggctattcatacaacc 960 tacgatttgttgcaacagaccatgattgatttgggtagacatccagagtacattgaacca 1020 ttaagacaagaagttgtccagttgttgagagaagaaggttggaaaaagactaccttgttc 1080 aagatgaagttgttggactccgctatcaaagaatcccaaagaatgaagccaggttctatc 1140 gttactatgagaagatacgttaccgaagatatcaccttgtcatctggtttgactttgaaa 1200 aagggtactagattgaacgtcgataacagaagattggacgatccaaagatctacgataac 1260 ccagaagtttacaacccatacagattctacgacatgagatctgaagctggtaaagatcat 1320 ggtgctcaattggtttctactggttctaatcatatgggtttcggtcatggtcaacattct 1380 tgtccaggtagattttttgctgccaacgaaatcaaagttgccttgtgtcatatcttggtt 1440 aagtacgattggaagttgtgtccagatactgaaactaagccagataccagaggtatgatt 1500 gctaaatcttctccagttaccgacattttgatcaagagaagagaatccgttgaattggat 1560 ttggaagccatctga 1575 SEQIDNO:80 MSIFNMITSYAGSQLLPFYIAIFVFTLVPWAIRFSWLELRKGSVVPLANPPDSLFGTGKT 60 RRSFVKLSREILAKARSLFPNEPFRLITDWGEVLILPPDFADEIRNDPRLSFSKAAMQDN 120 HAGIPGFETVALVGREDQLIQKVARKQLTKHLSAVIEPLSRESTLAVSLNFGETTEWRAI 180 RLKPAILDIIARISSRIYLGDQLCRNEAWLKITKTYTTNFYTASTNLRMFPRSIRPLAHW 240 FLPECRKLRQERKDAIGIITPLIERRRELRRAAIAAGQPLPVFHDAIDWSEQEAEAAGTG 300 ASFDPVIFQLTLSLLAIHTTYDLLQQTMIDLGRHPEYIEPLRQEVVQLLREEGWKKTTLF 360 KMKLLDSAIKESQRMKPGSIVTMRRYVTEDITLSSGLTLKKGTRLNVDNRRLDDPKIYDN 420 PEVYNPYRFYDMRSEAGKDHGAQLVSTGSNHMGFGHGQHSCPGRFFAANEIKVALCHILV 480 KYDWKLCPDTETKPDTRGMIAKSSPVTDILIKRRESVELDLEAI 524 SEQIDNO:81 atgaacaagtccaactctatgaacaacacctctttggaaaggttgttccaacaattggtt 60 ttgggtttggatggtatcccattgatggatgttcattggttgatctacgttgcttttggt 120 gcttggttgtgctcttacgttattcacgttttgtcctcttcatccactgttaaggttcca 180 gttgttggttacagatctgtttttgaacctacctggttgttgagattgagatttgtttgg 240 gaaggtggttccattattggtcaaggttacaacaagttcaaggactccattttccaagtc 300 agaaagttgggtactgatatcgttattatcccaccaaacttcatcgacgaagtgagaaaa 360 ttgtctcaagacaagaccagatctgtcgaaccattcattaacgattttgctggtcagtac 420 actaggggtatggtttttttacaatccgacttgcaaaacagagtcatccaacaaagattg 480 accccaaagttggtttctttgaccaaggttatgaaggaagaattggattacgccttgacc 540 aaagaaatcccagatatgaaggatgatgaatgggttgaagttgacatctcctccattatg 600 gttagattgatctccagaatttccgccagagtttttttgggtccagaacattgcagaaat 660 caagaatggttgactaacaccgctgaatactctgaatctttgttcattaccggtttcatc 720 ttgagagttgtcccacatatcttgaggccttttattgctccattattgccatcttacaga 780 accttgttgaggaacgtttcttctggtagaagagttatcggtgacatcatcagatctcaa 840 caaggtgatggtaacgaggatattttgtcttggatgagagatgctgctactggtgaagaa 900 aagcaaattgataacattgcccagagaatgttgatcttgtccttggcttctattcatacc 960 actgctatgactatgactcatgccatgtatgatttgtgtgctagaccagagtatatcgaa 1020 ccattgagagatgaagttaagggtgttgttgatgcttctggttgggataagactgctttg 1080 aatagattgcacagattggactcattcttgaaagaatcccaaagattcaacccagtgttc 1140 ttgttgactttcaacagaatctaccaccagtctatgactttgtctgatggtactaatttg 1200 ccatccggtactagaattgctgttccatctcatgctatgttgcaagattctgctcatgtt 1260 ccaggtccaactccaccaactgaatttgatggtttcaggtactccaagatcaggtctgat 1320 tctaattacgcccaaaagtacttgttctccatgaccgattcttctaatatggctttcggt 1380 tacggtaaatatgcttgtccaggtagattttacgcctccaacgaaatgaagttgaccttg 1440 gctattttgttgttgcagttcgaattcaagttgccagatggtaaaggtagaccaagaaac 1500 attaccatcgattccgatatgattccagatccaagagctagattgtgcgtcagaaaaaga 1560 tctttgagggacgaatga 1578 SEQIDNO:82 MNKSNSMNNTSLERLFQQLVLGLDGIPLMDVHWLIYVAFGAWLCSYVIHVLSSSSTVKVP 60 VVGYRSVFEPTWLLRLRFVWEGGSIIGQGYNKFKDSIFQVRKLGTDIVIIPPNFIDEVRK 120 LSQDKTRSVEPFINDFAGQYTRGMVFLQSDLQNRVIQQRLTPKLVSLTKVMKEELDYALT 180 KEIPDMKDDEWVEVDISSIMVRLISRISARVFLGPEHCRNQEWLTNTAEYSESLFITGFI 240 LRVVPHILRPFIAPLLPSYRTLLRNVSSGRRVIGDIIRSQQGDGNEDILSWMRDAATGEE 300 KQIDNIAQRMLILSLASIHTTAMTMTHAMYDLCARPEYIEPLRDEVKGVVDASGWDKTAL 360 NRLHRLDSFLKESQRFNPVFLLTFNRIYHQSMTLSDGTNLPSGTRIAVPSHAMLQDSAHV 420 PGPTPPTEFDGFRYSKIRSDSNYAQKYLFSMTDSSNMAFGYGKYACPGRFYASNEMKLTL 480 AILLLQFEFKLPDGKGRPRNITIDSDMIPDPRARLCVRKRSLRDE 525 SEQIDNO:83 atggcagaattagatacacttgatatagtagtattaggtgttatctttttgggtactgtg 60 gcatactttactaagggtaaattgtggggtgttaccaaggatccatacgctaacggattc 120 gctgcaggtggtgcttccaagcctggcagaactagaaacatcgtcgaagctatggaggaa 180 tcaggtaaaaactgtgttgttttctacggcagtcaaacaggtacagcggaggattacgca 240 tcaagacttgcaaaggaaggaaagtccagattcggtttgaacactatgatcgccgatcta 300 gaagattatgacttcgataacttagacactgttccatctgataacatcgttatgtttgta 360 ttggctacttacggtgaaggcgaaccaacagataacgccgtggatttctatgagttcatt 420 actggcgaagatgcctctttcaatgagggcaacgatcctccactaggtaacttgaattac 480 gttgcgttcggtctgggcaacaatacctacgaacactacaactcaatggtcaggaacgtt 540 aacaaggctctagaaaagttaggagctcatagaattggagaagcaggtgagggtgacgac 600 ggagctggaactatggaagaggactttttagcttggaaagatccaatgtgggaagccttg 660 gctaaaaagatgggcttggaggaaagagaagctgtatatgaacctattttcgctatcaat 720 gagagagatgatttgacccctgaagcgaatgaggtatacttgggagaacctaataagcta 780 cacttggaaggtacagcgaaaggtccattcaactcccacaacccatatatcgcaccaatt 840 gcagaatcatacgaacttttctcagctaaggatagaaattgtctgcatatggaaattgat 900 atttctggtagtaatctaaagtatgaaacaggcgaccatatcgcgatctggcctaccaac 960 ccaggtgaagaggtcaacaaatttcttgacattctagatctgtctggtaagcaacattcc 1020 gtcgtaacagtgaaagccttagaacctacagccaaagttccttttccaaatccaactacc 1080 tacgatgctatattgagataccatctggaaatatgcgctccagtttctagacagtttgtc 1140 tcaactttagcagcattcgcccctaatgatgatatcaaagctgagatgaaccgtttggga 1200 tcagacaaagattacttccacgaaaagacaggaccacattactacaatatcgctagattt 1260 ttggcctcagtctctaaaggtgaaaaatggacaaagataccattttctgctttcatagaa 1320 ggccttacaaaactacaaccaagatactattctatctcttcctctagtttagttcagcct 1380 aaaaagattagtattactgctgttgtcgaatctcagcaaattccaggtagagatgaccca 1440 ttcagaggtgtagcgactaactacttgttcgctttgaagcagaaacaaaacggtgatcca 1500 aatccagctccttttggccaatcatacgagttgacaggaccaaggaataagtatgatggt 1560 atacatgttccagtccatgtaagacattctaactttaagctaccatctgatccaggcaaa 1620 cctattatcatgatcggtccaggtaccggtgttgccccttttagaggcttcgtccaagag 1680 agggcaaaacaagccagagatggtgtagaagttggtaaaacactgctgttctttggatgt 1740 agaaagagtacagaagatttcatgtatcaaaaagagtggcaagagtacaaggaagctctt 1800 ggcgacaaattcgaaatgattacagctttttcaagagaaggatctaaaaaggtttatgtt 1860 caacacagactgaaggaaagatcaaaggaagtttctgatcttctatcccaaaaagcatac 1920 ttctacgtttgcggagacgccgcacatatggcacgtgaagtgaacactgtgttagcacag 1980 atcatagcagaaggccgtggtgtatcagaagccaagggtgaggaaattgtcaaaaacatg 2040 agatcagcaaatcaataccaagtgtgttctgatttcgtaactttacactgtaaagagaca 2100 acatacgcgaattcagaattgcaagaggatgtctggagttaa 2142 SEQIDNO:84 MAELDTLDIVVLGVIFLGTVAYFTKGKLWGVTKDPYANGFAAGGASKPGRTRNIVEAMEE 60 SGKNCVVFYGSQTGTAEDYASRLAKEGKSRFGLNTMIADLEDYDFDNLDTVPSDNIVMFV 120 LATYGEGEPTDNAVDFYEFITGEDASFNEGNDPPLGNLNYVAFGLGNNTYEHYNSMVRNV 180 NKALEKLGAHRIGEAGEGDDGAGTMEEDFLAWKDPMWEALAKKMGLEEREAVYEPIFAIN 240 ERDDLTPEANEVYLGEPNKLHLEGTAKGPFNSHNPYIAPIAESYELFSAKDRNCLHMEID 300 ISGSNLKYETGDHIAIWPTNPGEEVNKFLDILDLSGKQHSVVTVKALEPTAKVPFPNPTT 360 YDAILRYHLEICAPVSRQFVSTLAAFAPNDDIKAEMNRLGSDKDYFHEKTGPHYYNIARF 420 LASVSKGEKWTKIPFSAFIEGLTKLQPRYYSISSSSLVQPKKISITAVVESQQIPGRDDP 480 FRGVATNYLFALKQKQNGDPNPAPFGQSYELTGPRNKYDGIHVPVHVRHSNFKLPSDPGK 540 PIIMIGPGTGVAPFRGFVQERAKQARDGVEVGKTLLFFGCRKSTEDFMYQKEWQEYKEAL 600 GDKFEMITAFSREGSKKVYVQHRLKERSKEVSDLLSQKAYFYVCGDAAHMAREVNTVLAQ 660 IIAEGRGVSEAKGEEIVKNMRSANQYQVCSDFVTLHCKETTYANSELQEDVWS 713 SEQIDNO:85 atgatggatgataccacttctccatactctacctaccattccgttaggtccattagaaat 60 caatctgcttgggctttggctccaattgctgttttcatttgttacgttgtcttgagacac 120 aacagaaagtctgttccagctgcttctgctggttctcattctattttggaaccattgtgg 180 ttggccagattgagattcattagagactccagattcatcatcggtcaaggttactctaag 240 ttcaaggataccattttcaaggttaccaaggttggtgccgatattatagttgttgctcct 300 aagtacgtcgaagagatcagaagattgtctagagatactggtagatccgttgaaccattc 360 attcatgatttcgccggtgaattattgggtggtttgaattttttggagtccgacttgcaa 420 accagagttgttcaacaaaagttgaccccaaacttgaaaaccatcgttccagttatggaa 480 gatgagatgcattacgctttggtttccgaattggattcttgtttggatggttctgaacat 540 tggaccagagttgatatgatccacatgttgtctagaatcgtgtccagaatttccgccaga 600 attttcttgggtcctaagtactgtagaaacgacttgtggttgaaaactactgctgagtac 660 actgagaacttgttcttgactggtactttgttgagattcgtcccaagaatgttgcaaaaa 720 tggattgctccattgctaccatccttcagacaattgcaagaaaacagacaagctgccaga 780 aagatcatctctgaaattttgactgatcaccagccagaaaaacatgacgaaacatctgat 840 aatggtgatccatacccagatatcttgaccttgatgtttcaagctgctaggggtaaagaa 900 aaggacattgaagatattgcccaacacaccttgttgttgtccttatcttctattcatacc 960 accgctttgactatgactcaagccttgtatgatttgtgtgcttacccacaatatttggat 1020 ccagttaagcacgaaattgccgataccttgcaatctgaaggttcttggtctaaagctatg 1080 ttggataagttgcacatgatggacagtttgttgagagaatcccaaagattgtctccagtt 1140 ttcttgttgaccttcaacagaatcttgcatactccattgactttgtccaacggtattcat 1200 ttgccaaagggtactagaattgctgctccatctgatgctattttgaacgatccatctttg 1260 gttccaggtccacaaccagctgatacttttgatcctttcaggtacattaaccactctact 1320 ggtgatgctaaaaagaccaagactaacttccaaactacctccttgcaaaacatggctttt 1380 ggttatggtaaatacgcttgtccaggtagattttacgttgccaacgaaatcaaattggtc 1440 ttgggtcatttgttgatgcactacgaattcaaatttccaccaggtatgggtagaccagtt 1500 aactctactgttgatactgatatgtacccagatttgggtgccagattattggtcagaaaa 1560 agaaagatggaagaatga 1578 SEQIDNO:86 MMDDTTSPYSTYHSVRSIRNQSAWALAPIAVFICYVVLRHNRKSVPAASAGSHSILEPLW 60 LARLRFIRDSRFIIGQGYSKFKDTIFKVTKVGADIIVVAPKYVEEIRRLSRDTGRSVEPF 120 IHDFAGELLGGLNFLESDLQTRVVQQKLTPNLKTIVPVMEDEMHYALVSELDSCLDGSEH 180 WTRVDMIHMLSRIVSRISARIFLGPKYCRNDLWLKTTAEYTENLFLTGTLLRFVPRMLQK 240 WIAPLLPSFRQLQENRQAARKIISEILTDHQPEKHDETSDNGDPYPDILTLMFQAARGKE 300 KDIEDIAQHTLLLSLSSIHTTALTMTQALYDLCAYPQYLDPVKHEIADTLQSEGSWSKAM 360 LDKLHMMDSLLRESQRLSPVFLLTFNRILHTPLTLSNGIHLPKGTRIAAPSDAILNDPSL 420 VPGPQPADTFDPFRYINHSTGDAKKTKTNFQTTSLQNMAFGYGKYACPGRFYVANEIKLV 480 LGHLLMHYEFKFPPGMGRPVNSTVDTDMYPDLGARLLVRKRKMEE 525 SEQIDNO:87 atgaccaaccactcttcatcctactactacgaattctacaaggatcactcccacaccttt 60 agaagatctatgtctgagaataccttgatctcttcttgtttggctttggctacttgcgct 120 attttgttgtctattcaatggttgaagccacaaccattgatcatggttaatggtagaaag 180 ttcggtgagttgtccaatgttagagctaagagggattttacttttggtgctagacagttg 240 ttggagaagggttttaagatgtctccagataagccattcagaatcatgggtgatgttggt 300 gaattgcatattttgccaccaaagtacgcttacgaagtcagaaacaacgaaaagttgtct 360 ttcactatggctgctttcaagtggttttatgctcatttgccaggtttcgaaggtttcaga 420 gaaggtactaatgaatcccacatcatgaagttggttgccagacatcaattgactcatcaa 480 ttgacattggttaccggtgctgtttctgaagaatgtgctttggttttgaaggatgtttac 540 accgattctccagaatggcatgatattactgctaaggatgctaacatgaagttcatggct 600 agaatcaccttcagagtgttcttgggtaaagaaatgtgtagaaacccacagtggttgaga 660 attacttctacctatgctgttattgccttcagagctgttgaagaattgagattgtggcca 720 tcttggttaagaccagttgttcaatggtttatgccacattgcactcaatctagagctttg 780 gttcaagaagctagagatttgatcaaccctttgttggaaagaagaagagaagaaaaggct 840 gaagctgaaagaactggtgaaaaggttacttacaacgatgctgttgaatggttggatgat 900 ttggctagagaaaaaggtgttggttatgatccagcttgtgctcaattgtctttgtctgtt 960 gctgctttacattctaccactgatttcttcacccaagtcatgttcgatattgctcaaaac 1020 ccagaattgatcgaaccattgagagaagaaatcatctccgttttgggtaaacaaggttgg 1080 tctaagaactccttgtacaacttgaagttgatggactccgtcttgaaagaatcccaaaga 1140 ttgaagccaattgccattgcttctatgagaagattcactacccataacgttgaattgtcc 1200 gatggtgttattttgccaaagaacaagttgaccttggtttccgctcatcaacattgggat 1260 ccagaatattacaaggacccattgaagttcgatggttacagattcttcaacatgagaagg 1320 gaaccaggtaaagaatctaaggctcaattggtttctgctaccccagatcatatgggtttt 1380 ggttatggtttacatgcttgtccaggtagatttttcgcttccgaagaaatcaagattgcc 1440 ttgtcccatatcttgttgaagtacgattttaagccagtcgagggttcttctatggaacct 1500 agaaagtatggtttgaacatgaacgctaatccaaccgctaaattgtccgtcagaagaaga 1560 aaagaagagatcgccatttga 1581 SEQIDNO:88 MTNHSSSYYYEFYKDHSHTFRRSMSENTLISSCLALATCAILLSIQWLKPQPLIMVNGRK 60 FGELSNVRAKRDFTFGARQLLEKGFKMSPDKPFRIMGDVGELHILPPKYAYEVRNNEKLS 120 FTMAAFKWFYAHLPGFEGFREGTNESHIMKLVARHQLTHQLTLVTGAVSEECALVLKDVY 180 TDSPEWHDITAKDANMKFMARITFRVFLGKEMCRNPQWLRITSTYAVIAFRAVEELRLWP 240 SWLRPVVQWFMPHCTQSRALVQEARDLINPLLERRREEKAEAERTGEKVTYNDAVEWLDD 300 LAREKGVGYDPACAQLSLSVAALHSTTDFFTQVMFDIAQNPELIEPLREEIISVLGKQGW 360 SKNSLYNLKLMDSVLKESQRLKPIAIASMRRFTTHNVELSDGVILPKNKLTLVSAHQHWD 420 PEYYKDPLKFDGYRFFNMRREPGKESKAQLVSATPDHMGFGYGLHACPGRFFASEEIKIA 480 LSHILLKYDFKPVEGSSMEPRKYGLNMNANPTAKLSVRRRKEEIAI 526 SEQIDNO:89 atggccaaccattcttcatcctactaccatgaattctacaaggatcattcccataccgtt 60 ttgaccttgatgtctgaaaagccagttatcttgccatccttgattttgggtacttgtgct 120 gttttgttgtgcatccaatggttgaaaccacaaccattgattatggtcaacggtagaaag 180 ttcggtgaattgtctaatgttagagccaagagggattttacttttggtgccagacaattg 240 ctagagaagggtttgaaaatgtctccagataagccattcagaatcatgggtgatgttggt 300 gaattgcatattttgccaccaaagtacgcttacgaagtcagaaacaacgaaaagttgtct 360 ttcactatggctgctttcaagtggttttatgctcatttgccaggtttcgaaggtttcaga 420 gaaggtactaatgaatcccacatcatgaagttggttgccagacatcaattgactcatcaa 480 ttgacattggttaccggtgctgtttctgaagaatgtgctttggttttgaaggatgtttac 540 accgattctccagaatggcatgatattactgctaaggatgctaacatgaagttgatggct 600 agaatcacctctagagtgttcttgggtaaagaaatgtgtagaaacccacagtggttgaga 660 attacttctacctatgctgttattgccttcagagctgttgaagaattgagattgtggcca 720 tcttggttaagaccagttgttcaatggtttatgccacattgcactcaatctagagctttg 780 gttcaagaagctagagatttgatcaaccctttgttggaaagaagaagagaagaaaaggct 840 gaagctgaaagaactggtgaaaaggttacttacaacgatgctgttgaatggttggatgat 900 ttggctagagaaaaaggtgttggttatgatccagcttgtgctcaattgtctttgtctgtt 960 gctgctttacattctaccactgatttcttcacccaagtcatgttcgatattgctcaaaac 1020 ccagaattgatcgaaccattgagggaagaaattattgccgttttgggtaaacaaggctgg 1080 tctaagaattccttgtacaacttgaagttgatcgactccgtcttgaaagaatcccaaaga 1140 ttgaagccaattgccattgcttctatgagaagattcactacccataacgttaagttgtcc 1200 gatggtgttattttgccaaagaacaagttgaccttggtttccgctcatcaacattgggat 1260 ccagaatattacaaggacccattgaagttcgatggttacagattcttcaacatgagaagg 1320 gaaccaggtaaagaatctaaggctcaattggtttctgctaccccagatcatatgggtttt 1380 ggttatggtttacatgcttgtccaggtagatttttcgcttccgaagaaatcaagattgcc 1440 ttgtcccatatcttgttgaagtacgattttaagccagtcgagggttcttctatggaacct 1500 agaaagtatggtttgaacatgaacgctaatccaaccgctaaattgtccgtcagaagaaga 1560 aaagaagagatcgccatttga 1581 SEQIDNO:90 MANHSSSYYHEFYKDHSHTVLTLMSEKPVILPSLILGTCAVLLCIQWLKPQPLIMVNGRK 60 FGELSNVRAKRDFTFGARQLLEKGLKMSPDKPFRIMGDVGELHILPPKYAYEVRNNEKLS 120 FTMAAFKWFYAHLPGFEGFREGTNESHIMKLVARHQLTHQLTLVTGAVSEECALVLKDVY 180 TDSPEWHDITAKDANMKLMARITSRVFLGKEMCRNPQWLRITSTYAVIAFRAVEELRLWP 240 SWLRPVVQWFMPHCTQSRALVQEARDLINPLLERRREEKAEAERTGEKVTYNDAVEWLDD 300 LAREKGVGYDPACAQLSLSVAALHSTTDFFTQVMFDIAQNPELIEPLREEIIAVLGKQGW 360 SKNSLYNLKLIDSVLKESQRLKPIAIASMRRFTTHNVKLSDGVILPKNKLTLVSAHQHWD 420 PEYYKDPLKFDGYRFFNMRREPGKESKAQLVSATPDHMGFGYGLHACPGRFFASEEIKIA 480 LSHILLKYDFKPVEGSSMEPRKYGLNMNANPTAKLSVRRRKEEIAI 526 SEQIDNO:91 atgtccgccttccaaaaagaaaccgttttgtctgttagacactggaccgaatctttgttt 60 tcattcactgctactagagatccaggtttcagatttcaaaatggtcaattcgccatgatc 120 ggtttggaagttgaaggtaaaccattgatgagagcttactctatggcttctgctaatcat 180 gaagaagccttggaattcttctcaatcaaggttcaagatggtccattgacttccagattg 240 caaaagattagagaaggcgatatcatcttggttggtagaaaagctactggtactttgatt 300 accggtaacttgattccaggtaagaggttgttgttgttgtctactggtactggtttggct 360 ccatttgcttcattgattaaggatccagatgtctacgaaaactacgaaactatcgttttg 420 gctcatggttgcagacaagtttctgaattggcttatggtgaacacttggttgaaggtttg 480 agaaaccatgaatttttcggtccattgatcagagacaagttggtttattacccaaccgtt 540 actagagagccattcagaaatagaggtagaatcaccgatttgattgcctctaatcagttg 600 ttcgatgatattggtcaaggtggtttggatatcgaaaccgatagaattatgttgtgtggt 660 tctccaggtatgttggaagaattgcatgctatgtttgctgctagaggttttgttgaaggt 720 aatcattctcaaccaggtcacttcgttattgaaaaggctttcgttcagaggtaa 774 SEQIDNO:92 MSAFQKETVLSVRHWTESLFSFTATRDPGFRFQNGQFAMIGLEVEGKPLMRAYSMASANH 60 EEALEFFSIKVQDGPLTSRLQKIREGDIILVGRKATGILITGNLIPGKRLLLLSTGTGLA 120 PFASLIKDPDVYENYETIVLAHGCRQVSELAYGEHLVEGLRNHEFFGPLIRDKLVYYPTV 180 TREPFRNRGRITDLIASNQLFDDIGQGGLDIETDRIMLCGSPGMLEELHAMFAARGFVEG 240 NHSQPGHFVIEKAFVQR 257 SEQIDNO:93 atgaagcacatcgatgtcatgaacttcatctccaagatttgctcttggtctaaagattct 60 ccaggtttcgttttgttgatctccatcttggttatcttgggttccgttactttcattcca 120 aagtgtggtagaagatctgcttttgatgctttgccaatcgttaacaagccaaagtttggt 180 ccaatcttctccattattgctaggtggagattcatccaccaatccaagaaaattttggaa 240 gagggtcaaaagtgctactccaatagaccttttagaatttggactgattggggtgaagtt 300 ttgatgttgactccagattatgcccacgaaattagaaacgatccacacttgtctttttca 360 ggtgccgttaagattgatggtcatgctgatattccaggtttcgaaactgttaagttgatc 420 tcccatccagacaacttgattcaattggttgctagaaagcaattgaccagacatttggct 480 gctgttattcaaccattgtcctctgttactgaagaagccttgattaagaacttgggcaaa 540 tctcaagaatggtccgaaatctacttgaagtacgccgttttggatattatcgccagattg 600 tcatctaggatctactttggtgagttgttgtaccaaaacgaagagtggttgtctatcgtt 660 aagaattacgctactcatttcttcaccgcctcttccgatttgagaaaagttccatgggct 720 ttcagatctttggttcattggtttgttccatcttgcagagctttgagattggaaagatac 780 aacgctagaagagttttggaaccagttatctctcaaagaaggcaattgaaagaagctgct 840 aaaactgctggtggtactccattgcattttgaagatgctattgaatgggctgaagttgaa 900 gctagagttaagggtactaagtacgatccagttatcttccaattgaccttgtccttgttg 960 gctattcataccacttacgacttgttggaaatgtgcatgattgatttggctaaaagacca 1020 gactgcatcgaggacttgagaaaagaagttattaccgtcttgagaaaggatggttggaca 1080 aaaaatgccttgtacaacatgaagttgttggactccgctatcaaagaatcccaaagattg 1140 aaaccaggttccatcacttctatgagaagatacgctacttccgatgtccaattgagagat 1200 ggtgttgttttgaaaaagggcaacagattgaacgttttgaccttgcatagatccccagat 1260 ttgtttccatctccagatacttatgacccatacaggttctacaacattagaggtcaacca 1320 ggtaaagaaaactgggctcaattggtttctacctccgttgaacatatgggttttggtcat 1380 ggtgaacattcttgtccaggtagattttttgctgccaacgaaatcaaagttgccttggct 1440 catattttggttaagtacgattggaagttgtccgatgaagctggtggttgtactgaagtt 1500 aagggtatggttgaaaaagctggttccaaggttaagatcttggtcagacaaagacaagat 1560 gtcgaatccgttttggatgaagcttga 1587 SEQIDNO:94 MKHIDVMNFISKICSWSKDSPGFVLLISILVILGSVTFIPKCGRRSAFDALPIVNKPKFG 60 PIFSIIARWRFIHQSKKILEEGQKCYSNRPFRIWTDWGEVLMLTPDYAHEIRNDPHLSFS 120 GAVKIDGHADIPGFETVKLISHPDNLIQLVARKQLTRHLAAVIQPLSSVTEEALIKNLGK 180 SQEWSEIYLKYAVLDIIARLSSRIYFGELLYQNEEWLSIVKNYATHFFTASSDLRKVPWA 240 FRSLVHWFVPSCRALRLERYNARRVLEPVISQRRQLKEAAKTAGGTPLHFEDAIEWAEVE 300 ARVKGTKYDPVIFQLTLSLLAIHTTYDLLEMCMIDLAKRPDCIEDLRKEVITVLRKDGWT 360 KNALYNMKLLDSAIKESQRLKPGSITSMRRYATSDVQLRDGVVLKKGNRLNVLTLHRSPD 420 LFPSPDTYDPYRFYNIRGQPGKENWAQLVSTSVEHMGFGHGEHSCPGRFFAANEIKVALA 480 HILVKYDWKLSDEAGGCTEVKGMVEKAGSKVKILVRQRQDVESVLDEA 528 SEQIDNO:95 atggatgttcaagatacaaccgctgcttgtcatgatgcttttgctgaattggcttctcca 60 gcttgtattcaagatccatatcctttcatgagatggttgagagaacatgatccagttcat 120 agagctgcttcaggtttgtttttgttgtctagacatgctgatatctactgggcttttaaa 180 gctactggtgatgcttttagaggtccagctccatctgaattggctagatattttccaaga 240 gctgcctcttctttgtccttgaatttgttggcttctaccttggctatgaaggaaccacca 300 actcatacaagattgagaagattgatctccagagatttcaccgttggtcaaattgataat 360 ttgaggccatccattgctagaatcgttgctgctagattggatggtatggctccagctttg 420 gaaagaggtgaagctgttgacttgcatagagaatttgctttggctttgccaatgttggtt 480 tttgctgaactatttggtatgccacaagacgacgtttttgaattgtctgctatcgtttcc 540 gctatcttggaaggtttgtctccacatgcttcagatccacaattggctgctgctgatgtt 600 gcttctgctagagttaaggcttatttcggtgatttgatcttgagaaagagagccgatcca 660 agaagagatatcgtttctactttggttggtgctcatactgatgatgctgatactttgtct 720 gatgccgaattgatttctatgttgtggggtatgttgttgggtggttttgctactactgct 780 gctactattgatcatgctgttttggctatgttggcttacccagaagaaagacattggttg 840 caaggtgatgctgctggtgttgaagcttttgttgaagaggttttgagatgtgaagctcca 900 gctatgttttcctcaattccaagaattgcccaaagggatattgaattgcatggtgttgtt 960 attccaaaggatgccgatgttagagttttgattgctgctggtaatagagatccagatgca 1020 tttgctgatccagatagatttgatccagttaggttttacggtactagaccaggtatgtca 1080 tctgatggtaagatcatgttgtctttcggtcatggtattcatttctgtttgggtgctcaa 1140 ttggctagagttcaattggctgaatctttgccacaaattcaagctagatttccaactttg 1200 gctttggctgaacaacctactagagaaccatctgcttttttgagaactttcagagctttg 1260 ccagttagattgcatgctcaagctgctgctgaagttagagttgttgttgatcaagatttg 1320 tgtggtactaccggtcaatgtgttttgactttgccaggtacttttagacaaagggaacca 1380 gatggtgttgctgaagtatgtatggctactgttccacaagctttacatgctgctgttaga 1440 ttggctgcttctcaatgtccagttgctgctattagagttattgaatctgaagctggtgat 1500 gatcattgcactaatccaggtccaacaccatctccagctgatgctgaaagacatgctgct 1560 aaagatttgagaaatccaggtgaacatgacggcactatttga 1602 SEQIDNO:96 MDVQDTTAACHDAFAELASPACIQDPYPFMRWLREHDPVHRAASGLFLLSRHADIYWAFK 60 ATGDAFRGPAPSELARYFPRAASSLSLNLLASTLAMKEPPTHTRLRRLISRDFTVGQIDN 120 LRPSIARIVAARLDGMAPALERGEAVDLHREFALALPMLVFAELFGMPQDDVFELSAIVS 180 AILEGLSPHASDPQLAAADVASARVKAYFGDLILRKRADPRRDIVSTLVGAHTDDADTLS 240 DAELISMLWGMLLGGFATTAATIDHAVLAMLAYPEERHWLQGDAAGVEAFVEEVLRCEAP 300 AMFSSIPRIAQRDIELHGVVIPKDADVRVLIAAGNRDPDAFADPDRFDPVRFYGTRPGMS 360 SDGKIMLSFGHGIHFCLGAQLARVQLAESLPQIQARFPTLALAEQPTREPSAFLRTFRAL 420 PVRLHAQAAAEVRVVVDQDLCGTTGQCVLTLPGTFRQREPDGVAEVCMATVPQALHAAVR 480 LAASQCPVAAIRVIESEAGDDHCTNPGPTPSPADAERHAAKDLRNPGEHDGTI 533 SEQIDNO:97 atggttgttgttgttgctgcagctatggctgctgcttctttgtgttgtggtgttgctgct 60 tacttgtattacgttttgtggttggctccagaaagattgagagcacatttgagaaggcaa 120 ggtattggtggtccaactccatcttttccatatggtaatttggccgatatgagatcacat 180 gctgctgctgcagctggtggtaaagctactggtgaaggtagacaagagggtgatatagtt 240 catgattacagacaagctgtgttcccattctacgaaaattggagaaaacaatacggtcca 300 gtgttcacttactctgttggtaatatggttttcttgcacgtttccagaccagatatcgtt 360 agagaattgtctttgtgcgtttccttggacttgggtaaatcttcttatatgaaggctacc 420 caccaacctttgtttggtgaaggtattttgaagtctaatggtaacgcttgggctcaccaa 480 agaaaattgattgctccagaattcttcccagataaggttaagggtatggttgatttgatg 540 gttgattccgctcaagtcttggtttcttcatgggaagatagaatcgatagatctggtggt 600 aatgccttggatttgatgatcgatgatgatatcagagcttactccgccgatgttatttct 660 agaacttgtttcggttcctcctacgttaagggtaagcaaattttcgacatgatcagagag 720 ttgcaaaagaccgtttctaccaagaagcaaaacttgttggctgaaatgactggcttgtct 780 tttttgtttccaaaggcttctggtagagctgcttggagattgaatggtagagttagagct 840 ttgattttggacttggttggtgaaaatggtgaagaggatggtggtaatttgttgtctgct 900 atgttgagatctgctagaggtggtggtggtggcggtggtgaagttgcagctgctgctgaa 960 gattttgttgttgataactgcaagaacatctacttcgctggttatgaatctactgctgtt 1020 actgctgcttggtgtttgatgttgttggctttacatccagaatggcaagatagagttaga 1080 gatgaagttcaagctgcttgttgcggtggtggtggaagatctccagattttccagcttta 1140 caaaagatgaagaacttgaccatggtgatccaagaaactttgagattatatccagctggt 1200 gccgttgtttctagacaagctttgagagaattatccttgggtggtgttagagttccaaga 1260 ggtgttaatatctacgttccagtttctaccttgcatttggatgctgaattgtggggtggt 1320 ggtgctggtgctgctgaatttgatccagctagatttgctgatgctagaccaccattgcat 1380 gcttatttgccatttggtgccggtgctagaacatgtttgggtcaaacttttgctatggcc 1440 gaattgaaggttttgttgtctttggttttgtgcagattcgaagttgctttgtctccagaa 1500 tatgttcattctccagctcacaagttgatcgttgaagctgaacatggtgttagattggtc 1560 ttgaagaaagtcagatctaagtgtgattgggctggtttcgattga 1605 SEQIDNO:98 MVVVVAAAMAAASLCCGVAAYLYYVLWLAPERLRAHLRRQGIGGPTPSFPYGNLADMRSH 60 AAAAAGGKATGEGRQEGDIVHDYRQAVFPFYENWRKQYGPVFTYSVGNMVFLHVSRPDIV 120 RELSLCVSLDLGKSSYMKATHQPLFGEGILKSNGNAWAHQRKLIAPEFFPDKVKGMVDLM 180 VDSAQVLVSSWEDRIDRSGGNALDLMIDDDIRAYSADVISRTCFGSSYVKGKQIFDMIRE 240 LQKTVSTKKQNLLAEMTGLSFLFPKASGRAAWRLNGRVRALILDLVGENGEEDGGNLLSA 300 MLRSARGGGGGGGEVAAAAEDFVVDNCKNIYFAGYESTAVTAAWCLMLLALHPEWQDRVR 360 DEVQAACCGGGGRSPDFPALQKMKNLTMVIQETLRLYPAGAVVSRQALRELSLGGVRVPR 420 GVNIYVPVSTLHLDAELWGGGAGAAEFDPARFADARPPLHAYLPFGAGARTCLGQTFAMA 480 ELKVLLSLVLCRFEVALSPEYVHSPAHKLIVEAEHGVRLVLKKVRSKCDWAGFD 534 SEQIDNO:99 atggctcaattggataccttggatatcgttgttttggctgctttgccattgggtactgtt 60 gcttattttactaagggtacttactgggctgtttctgctgatccatatgctaatccattg 120 actaatgctaatggtgctgctagagctggtaagtccagaaacattattgaaaagttggaa 180 gaatccgacaagaactgcgttgttttttacggttctcaaactggtactgctgaagattat 240 gcttccaggttgtctaaagaaggtcattctagattcggtttgaacaccatggttgctgat 300 ttggaagaatacgatttcgacaacttggactcattcccagaagataagttggctgttttt 360 gttttggctacttatggtgaaggtgaacctactgataatgccgttgaattctacgaattc 420 atcggttccgaagatatcactttttctgatggtggttccatcgatgataagccattgtct 480 aagttgaactacgttgcttttggtttgggtaacaacacctacgaacattacaactccatg 540 gttagaaacgtcgataagtacttgacaaagttgggtgctactagattgggttctgccggt 600 gaaggtgatgatggtgctggtactatggaagaagattttttggcttggaaagaacctatg 660 tgggctgctgttgctgaaaagatgaatttggaagaaagagaagctgaatacgaagccgtt 720 ttcgaagttactgaaaagccagatttgaacgctcaagatgatactgtttatttgggtgag 780 ccaaacaagaaccacttggaaggtaatcaaaagggtccattcaatgctaacaacccattc 840 attgctccaatcgttgaatctcatgaactattcaccaccaaagaaagaaactgcttgcac 900 atggaaattagcattggtggttctaacttgtcttacactaccggtgatcatattgctatt 960 tggccaaacaatgccggtaaagaagttgacagattcttcaaggttttgggcaaagaagat 1020 aagagacataccgttattgctgtcagaggtttggatccaactgctaaagttccatttcca 1080 tctccaactacttatgatgctgctgttagattccatttggaaattggtgctgctgtctct 1140 agacaattggtttctactattgctcaattcgccccaaacgaagatattaaggctgaaatg 1200 gctaaattgggttccgataaggattacttcaagttgcaagttaccgacagaaacttgaat 1260 ttggctcagttgttggaaatttgcggtaaaggtcaaccatggactaagattccattctcc 1320 tttatgttcgaatccttgttgaagattcagccaaggtactactccatctcttcttcatct 1380 ttggttcagaaggacaaggtttctattaccgctgttgttgaatctttggaaagaccaggt 1440 gctccacatgttttgaaaggtgttactaccaattacttgttggccttgaagcaaaagcaa 1500 catggtgatccaaatccagatccacatggtttgaattacgctattactggtccaagaaac 1560 aagtacgatggtatccatgttccagttcatgttagacactctaacttcaaattgccatcc 1620 gatccatctaagccaatagttatggttggtccaggtactggtgttgctccttttagaggt 1680 tttgttcaagaaagagctgctcaagctaaagctggtcataatgttggtaagaccattttg 1740 ttcttcggttgcagaaaagcctctgaggatttcttgtatcaaaatgaatgggcccagtac 1800 aaagaagctttgggagataatttcgaaatctacaccgctttctctagagatggtccaaaa 1860 aaggtttacgtccagaaccatttggaagaacatggtgaagaagttaacaggttgttggaa 1920 aaaaaggcctacttctacgtttgtggtgatgctgctcatatggctagagatgttaatacc 1980 ttgttgggcaagttgatctccaagtacagaaatgtctctgaaactaagggtgaagaaatc 2040 gttaaggctatgagagcctctaatcagtaccaagaagatgtttggtcttaa 2091 SEQIDNO:100 MAQLDTLDIVVLAALPLGTVAYFTKGTYWAVSADPYANPLTNANGAARAGKSRNIIEKLE 60 ESDKNCVVFYGSQTGTAEDYASRLSKEGHSRFGLNTMVADLEEYDFDNLDSFPEDKLAVF 120 VLATYGEGEPTDNAVEFYEFIGSEDITFSDGGSIDDKPLSKLNYVAFGLGNNTYEHYNSM 180 VRNVDKYLTKLGATRLGSAGEGDDGAGTMEEDFLAWKEPMWAAVAEKMNLEEREAEYEAV 240 FEVTEKPDLNAQDDTVYLGEPNKNHLEGNQKGPFNANNPFIAPIVESHELFTTKERNCLH 300 MEISIGGSNLSYTTGDHIAIWPNNAGKEVDRFFKVLGKEDKRHTVIAVRGLDPTAKVPFP 360 SPTTYDAAVRFHLEIGAAVSRQLVSTIAQFAPNEDIKAEMAKLGSDKDYFKLQVTDRNLN 420 LAQLLEICGKGQPWTKIPFSFMFESLLKIQPRYYSISSSSLVQKDKVSITAVVESLERPG 480 APHVLKGVTTNYLLALKQKQHGDPNPDPHGLNYAITGPRNKYDGIHVPVHVRHSNFKLPS 540 DPSKPIVMVGPGTGVAPFRGFVQERAAQAKAGHNVGKTILFFGCRKASEDFLYQNEWAQY 600 KEALGDNFEIYTAFSRDGPKKVYVQNHLEEHGEEVNRLLEKKAYFYVCGDAAHMARDVNT 660 LLGKLISKYRNVSETKGEEIVKAMRASNQYQEDVWS 696 SEQIDNO:101 atgccaggtaagattgaaaacggtactccaaaggatttgaaaaccggtaacgattttgtt 60 tccgctgctaagtctttgttggatagagcttttaagtcccaccattcttactacggtttg 120 tgttctacttcttgccaagtttatgatactgcttgggttgctatgattccaaagactaga 180 gataacgtcaagcaatggttgttcccagaatgtttccactacttgttgaaaactcaagct 240 gctgatggttcttggggttctttgccaactactcaaactgctggtattttggatactgct 300 tctgctgttttggctttgttgtgtcatgctcaagaaccattgcaaatcttggatgtttct 360 ccagacgaaatgggtttgagaattgaacatggtgttaccagcttgaagagacaattggct 420 gtttggaatgatgtcgaagataccaaccatatcggtgtcgaattcattattccagccttg 480 ttgtccatgttggaaaaagaattggatgtcccatctttcgaattcccatgcagatctatt 540 ttggaaagaatgcacggtgaaaagttgggtcatttcgatttggaacaagtttacggtaag 600 ccatcctctttgttgcattctttggaagctttcttgggcaagttggatttcgatagattg 660 tctcatcacttgtaccacggttctatgatggcttctccatcttctactgctgcttatttg 720 attggtgctactaagtgggatgatgaagctgaagattacttgagacacgttatgagaaat 780 ggtgctggtcatggtaatggtggtatttctggtacttttccaactacccatttcgaatgc 840 tcttggattattgctaccttgttgaaggttggtttcaccttgaaacaaatcgatggtgat 900 ggtttgagaggtttgtctaccattttgttggaagctttgagagatgagaacggtgttatt 960 ggttttgctccaagaactgctgatgttgatgatactgctaaagctttgttggccttgtcc 1020 ttggttaatcaaccagtttctccagatatcatgatcaaggttttcgaaggtaaggatcat 1080 ttcactaccttcggttctgaaagagatccatctttgacttccaacttgcacgttttgttg 1140 tccttgttgaagcagtctaacttgtctcaataccacccacaaattctaaagactaccttg 1200 ttcacttgtagatggtggtggggttctgatcattgtgttaaggataagtggaacttgtct 1260 cacttgtacccaactatgttgttggttgaagctttcactgaagtcttgcatttgattgac 1320 ggtggtgaattgtcctctttgttcgatgaatctttcaagtgcaagatcggcttgtctatt 1380 ttccaagctgttttgagaatcatcttgacccaagataatgacggttcttggagaggttat 1440 agagaacaaacttgctacgctatcttggctttggttcaagctagacatgtttgtttcttc 1500 acccacatggttgatagattgcaatcctgtgttgatagaggtttctcttggttgaagtct 1560 tgctctttccattcccaagatttgacttggacttctaagactgcttacgaagttggtttt 1620 gttgctgaagcttacaaattggctgctttacaatctgcctctttggaagttccagctgct 1680 actattggtcattctgttacttcagctgttccatcttctgatttggagaagtacatgaga 1740 ttggttagaaagaccgctttgttctctccattggatgaatggggtttgatggcctctatt 1800 atcgaatcttctttcttcgtgccattgctacaagctcaaagagttgaaatctacccaaga 1860 gataacatcaaggtcgacgaagataagtacttgtccattattccattcacctgggttggt 1920 tgtaacaacagatctagaactttcgcttctaacagatggttgtacgacatgatgtacttg 1980 tctttgttgggttaccaaaccgatgagtatatggaagctgttgctggtccagtttttggt 2040 gatgtttctttgttgcaccaaaccatcgataaggttattgataacaccatgggtaacttg 2100 gctagagctaatggtactgttcattctggtaatggtcatcaacatgagtctccaaacatt 2160 ggtcaagttgaagatactttgaccaggttcactaactcttttttgaaccacaaggatgtc 2220 ttgaactcctcatcttctgatcaagataccttgagaagagaattcagaaccttcatgcat 2280 gcccatattacccaaatcgaagataactccagattctccaaacaagcttcttctgatgct 2340 ttctcatctccagaacaatcttacttccaatgggttaattctaccggtggttctcatgtt 2400 gcttgtgcttattcttttgctttctccaactgtttgatgtccgctaatttgttgcaaggt 2460 aaggatgcttttccatccggtactcaaaagtacttgatctcctctgttatgagacatgct 2520 accaacatgtgtagaatgtacaacgatttcggttccattgctagagataatgccgaaaga 2580 aacgttaactccattcacttcccagaattcactttgtgtaacggtacttctcaaaacttg 2640 gacgaaagaaaagagaggttgttgaagattgctacctacgaacaaggttacttggataga 2700 gcattggaagccttggaaagacaatctagagatgatgctggtgatagagctggttctaaa 2760 gatatgagaaagttgaagatcgtcaagttgttctgtgatgttaccgacttgtatgatcag 2820 ttgtacgttatcaaggacttgtcctcttcaatgaagtaa 2859 SEQIDNO:102 MPGKIENGTPKDLKTGNDFVSAAKSLLDRAFKSHHSYYGLCSTSCQVYDTAWVAMIPKTR 60 DNVKQWLFPECFHYLLKTQAADGSWGSLPTTQTAGILDTASAVLALLCHAQEPLQILDVS 120 PDEMGLRIEHGVTSLKRQLAVWNDVEDTNHIGVEFIIPALLSMLEKELDVPSFEFPCRSI 180 LERMHGEKLGHFDLEQVYGKPSSLLHSLEAFLGKLDFDRLSHHLYHGSMMASPSSTAAYL 240 IGATKWDDEAEDYLRHVMRNGAGHGNGGISGTFPTTHFECSWIIATLLKVGFTLKQIDGD 300 GLRGLSTILLEALRDEGNIVGFAPRTADVDDTAKALLALSLVNQPVSPDIMIKVFEGKDH 360 FTTFGSERDPSLTSNLHVLLSLLKQSNLSQYHPQILKTTLFTCRWWWGSDHCVKDKWNLS 420 HLYPTMLLVEAFTEVLHLIDGGELSSLFDESFKCKIGLSIFQAVLRIILTQDNDGSWRGY 480 REQTCYAILALVQARHVCFFTHMVDRLQSCVDRGFSWLKSCSFHSQDLTWTSKTAYEVGF 540 VAEAYKLAALQSASLEVPAATIGHSVTSAVPSSDLEKYMRLVRKTALFSPLDEWGLMASI 600 IESSFFVPLLQAQRVEIYPRDNIKVDEDKYLSIIPFTWVGCNNRSRTFASNRWLYDMMYL 660 SLLGYQTDEYMEAVAGPVFGDVSLLHQTIDKVIDNTMGNLARANGTVHSGNGHQHESPNI 720 GQVEDTLTRFTNSVLNHKDVLNSSSSDQDTLRREFRTFMHAHITQIEDNSRFSKQASSDA 780 FSSPEQSYFQWVNSTGGSHVACAYSFAFSNCLMSANLLQGKDAFPSGTQKYLISSVMRHA 840 TNMCRMYNDFGSIARDNAERNVNSIHFPEFTLCNGTSQNLDERKERLLKIATYEQGYLDR 900 ALEALERQSRDDAGDRAGSKDMRKLKIVKLFCDVTDLYDQLYVIKDLSSSMK 952 SEQIDNO:103 atgcacattttgacttacccatccggtaagattgaaaacggtactccaaaggatttgaaa 60 accggtaacgattttgtttccgctgctaagtctttgttggatagagcttttaagtcccac 120 cattcttactacggtttgtgttctacttcttgccaagtttatgatactgcttgggttgct 180 atgattccaaagactagagataacgtcaagcaatggttgttcccagaatgtttccactac 240 ttgttgaaaactcaagctgctgatggttcttggggttctttgccaactactcaaactgct 300 ggtattttggatactgcttctgctgttttggctttgttgtgtcatgctcaagaaccattg 360 caaatcttggatgtttctccagacgaaatgggtttgagaattgaacatggtgttaccagc 420 ttgaagagacaattggctgtttggaatgatgtcgaagataccaaccatatcggtgtcgaa 480 ttcattattccagccttgttgtccatgttggaaaaagaattggatgtcccatctttcgaa 540 ttcccatgcagatctattttggaaagaatgcacggtgaaaagttgggtcatttcgatttg 600 gaacaagtttacggtaagccatcctctttgttgcattctttggaagctttcttgggcaag 660 ttggatttcgatagattgtctcatcacttgtaccacggttctatgatggcttctccatct 720 tctactgctgcttatttgattggtgctactaagtgggatgatgaagctgaagattacttg 780 agacacgttatgagaaatggtgctggtcatggtaatggtggtatttctggtacttttcca 840 actacccatttcgaatgctcttggattattgctactttgttgaagggtggtttcaccttg 900 aaacaaattgatggtgatggtttgagaggcttgtctaccattttgttggaagctttgaga 960 gatgagaacggtgttattggttttgctccaagaactgctgatgttgatgatactgctaaa 1020 gctttgttggccttgtccttggttaatcaaccagtttctccagatatcatgatcaagggt 1080 tttgaaggtaaggatcatttcactaccttcggttctgaaagagatccatctttgacttcc 1140 aacttgcacgttttgttgtctttgccaggtaagcaatctaacttgtctcaataccatcca 1200 cagatcttgaaaactaccttgttcacttgtagatggtggtggggttctgatcattgtgtt 1260 aaggataagtggaacttgtctcacttgtacccaactatgttgttggttgaagctttcact 1320 gaagtcttgcatttgattgacggtggtgaattgtcctctttgttcgatgaatctttcaag 1380 tgcaagatcggcttgtctattttccaagctgttttgagaatcatcttgacccaagataat 1440 gacggttcttggagaggttatagagaacaaacttgctacgctatcttggctttggttcaa 1500 gctagacatgtttgtttcttcacccacatggttgatagattgcaatcctgtgttgataga 1560 ggtttctcttggttgaagtcttgctctttccattcccaagatttgacttggacttctaag 1620 actgcttacgaagttggttttgttgctgaagcttacaaattggctgctttacaatctgcc 1680 tctttggaagttccagctgctactattggtcattctgttacttcagctgttccatcttct 1740 gatttggagaagtacatgagattggttagaaagaccgctttgttctctccattggatgaa 1800 tggggtttgatggcctctattatcgaatcttctttcttcgtgccattgctacaagctcaa 1860 agagttgaaatctacccaagagataacatcaaggtcgacgaagataagtacttgtccatt 1920 attccattcacctgggttggttgtaacaacagatctagaactttcgcttctaacagatgg 1980 ttgtacgacatgatgtacttgtctttgttgggttaccaaaccgatgagtatatggaagct 2040 gttgctggtccagtttttggtgatgtttctttgttgcaccaaaccatcgataaggttatt 2100 gataacaccatgggtaacttggctagagctaatggtactgttcattctggtaatggtcat 2160 caacatgagtctccaaacattggtcaagttgaagatactttgaccaggttcactaactct 2220 gttttgaaccacaaggatgtcttgaactcctcatcttctgatcaagataccttgagaaga 2280 gaattcagaaccttcatgcatgcccatattacccaaatcgaagataactccagattctcc 2340 aaacaagcttcttctgatgctttctcatctccagaacaatcttacttccaatgggttaat 2400 tctaccggtggttctcatgttgcttgtgcttattcttttgctttctccaactgtttgatg 2460 tccgctaatttgttgcaaggtaaggatgcttttccatccggtactcaaaagtacttgatc 2520 tcctctgttatgagacatgctaccaacatgtgtagaatgtacaacgatttcggttccatt 2580 gctagagataatgccgaaagaaacgttaactccattcacttcccagaattcactttgtgt 2640 aacggtacttctcaaaacttggacgaaagaaaagagaggttgttgaagattgctacctac 2700 gaacaaggttacttggatagagcattggaagccttggaaagacaatctagagatgatgct 2760 ggtgatagagctggttctaaagatatgagaaagttgaagatcgtcaagttgttctgtgat 2820 gttaccgactttatgatcagttgtacgttatcaaggacttgtcctcttcaatgaagtaa 2880 SEQIDNO:104 MHILTYPSGKIENGTPKDLKTGNDFVSAAKSLLDRAFKSHHSYYGLCSTSCQVYDTAWVA 60 MIPKTRDNVKQWLFPECFHYLLKTQAADGSWGSLPTTQTAGILDTASAVLALLCHAQEPL 120 QILDVSPDEMGLRIEHGVTSLKRQLAVWNDVEDTNHIGVEFIIPALLSMLEKELDVPSFE 180 FPCRSILERMHGEKLGHFDLEQVYGKPSSLLHSLEAFLGKLDFDRLSHHLYHGSMMASPS 240 STAAYLIGATKWDDEAEDYLRHVMRNGAGHGNGGISGTFPTTHFECSWIIATLLKGGFTL 300 KQIDGDGLRGLSTILLEALRDENGVIGFAPRTADVDDTAKALLALSLVNQPVSPDIMIKG 360 FEGKDHFTTFGSERDPSLTSNLHVLLSLPGKQSNLSQYHPQILKTTLFTCRWWWGSDHCV 420 KDKWNLSHLYPTMLLVEAFTEVLHLIDGGELSSLFDESFKCKIGLSIFQAVLRIILTQDN 480 DGSWRGYREQTCYAILALVQARHVCFFTHMVDRLQSCVDRGFSWLKSCSFHSQDLTWTSK 540 TAYEVGFVAEAYKLAALQSASLEVPAATIGHSVTSAVPSSDLEKYMRLVRKTALFSPLDE 600 WGLMASIIESSFFVPLLQAQRVELYPRDNIKVDEDKYLSIIPFTWVGCNNRSRTFASNRW 660 LYDMMYLSLLGYQTDEYMEAVAGPVFGDVSLLHQTIDKVIDNTMGNLARANGTVHSGNGH 720 QHESPNIGQVEDTLTRFTNSVLNHKDVLNSSSSDQDTLRREFRTFMHAHITQIEDNSRFS 780 KQASSDAFSSPEQSYFQWVNSTGGSHVACAYSFAFSNCLMSANLLQGKDAFPSGTQKYLI 840 SSVMRHATNMCRMYNDFGSIARDNAERNVNSIHFPEFTLCNGTSQNLDERKERLLKIATY 900 EQGYLDRALEALERQSRDDAGDRAGSKDMRKLKIVKLFCDVTDLYDQLYVIKDLSSSMK 959 SEQIDNO:105 atgttggaaggtattggtatcggttcttctccacaatctttgttggattctgccaaggat 60 ttgattgctgaagcttgttctagaaccgatccattttatggtttgtctaccgcttcttgt 120 caaacttatgatactgcttgggttgccatggttgttaagagattggaatctggtgaagat 180 gcttgggctttcccacaatcttttaggtatattttggaagcccaaacttctggtggtggt 240 tggggtgatccaaaagcttctaaaactgttggtattttggataccgctgctgctttgttg 300 gcattatacagacatttggatagaccattgcaaatcaccgaagttaccagaatggatgtc 360 gaatccagaattgaaaaggcttctacctctttggtgtcccaattgcaacaatgggatgat 420 ttggttgaatccaaccatatcggtgtcgaattgattttgccttccttgttggaacaattg 480 agacaaatcaatccagtcttgcactctactagattcaaggctgaacaagatttgaccaga 540 atgcacgaagaaaagttgagacacttcgatgtctctagcttgtattcttctagaccatct 600 tctgccttgcattctttggaagcttttttgggtaaattggacttcgatagagttggtcat 660 cacttgtatcatggttctatgatggcttctccatcttctactgctgcttatttgattggt 720 gcttctacttacgattctaccgctgaagcttacttgtcccatattttgaaatgtaccgct 780 aaaggttctccaggtggtattccaggtactttcccaattactaatttcgaatactcctgg 840 attaccgccactttgttgagagattgctttgcttatgaagatttggctggtccatctttg 900 gattgcattggtcaaactttggaagaagctttacaagctggtaagggtgttattggtttt 960 gctccaagaactgctgatgttgatgatactgctaaaggtttgttggctttgacctctatg 1020 agaagatatggtcatgctgatccaaagccaatgatcaaggttttcgaaagagaagatcat 1080 ttcaccaccttcggttctgaaagagatccatcttttacctctaactgccacgttttgttg 1140 tctttgttggctcaagaatctgacttgccattatacagagcccaaatctacaaggctact 1200 aagttcttgtgtgacttcttgttctatagggatggtccattgaaagataagtggcatatg 1260 acttcatcctacccatctatgttgttggttgaagctttttccgagttgttgagattgcaa 1320 gacgaacaaaagttcgaacagttgttgacctctgatgaacaacacagagttttcatcgtt 1380 ttgttccaaacctgtttgagaaccttgttggtccaatctgaagatggttcttggtctggt 1440 tgtactgaacaaacttctcatgctgtatgtactttggctagagcttggagattgaacttg 1500 ttcattgacttaagaccagacttgcaagttgctattcaagccggtattcaatacttggat 1560 agacctgaagctcaaatgggtcaaaactggacttctaagactgtttactccgttgatttg 1620 gttggtaaggcttacattttggctgctagaaaaatggcccaagatttgtctgatagaact 1680 ccatttggtcctaagagggaagatttcatgtctttgaagaagttcaccacctacttggaa 1740 acctctaaaagattgccattattgcaagctactccaccttggcaaattattgcttctttg 1800 actgaatccgctttgttcttgcctttgttgaggaaagaaaaagaagccatctttccaagg 1860 gatggtactatgttgactccagatgattacttggatatcattccatacacctgggttatt 1920 tgcggtaacagaattgatgttcatacctctccatctttggccttggatatgatgttgttg 1980 tctatgtacggttaccagaacgacgaattctttgaaactcatgctatggctggtcattac 2040 caatctggttctgatttgaagagattggttgatgatgtcttgcaacagaacattccaaaa 2100 tgtgctgaaccatctaacggttcttctaaacatgatactggtaaccagtctagaactgct 2160 caagaagctgctatttctttgccagaaatgtctgctggtttgaacagattcatctcctac 2220 atcttgaaacatccattggttgctcaagctcatccaaactctaaatccgaattgcacaga 2280 gaattgcaagctttcttgcatgctcattctgatcaatctgacgaaaacagaagattcgct 2340 gcccaagaagaaaaagacgaattgcaatctccatcccaaaccttgtttcaatacgttaga 2400 tctactggtggtgatcatgttgcttgtgcttactctttgtctttcatgttgtgcatcatc 2460 tcttcatccttgtgtgatggtggtgaagtttttcaaactgccgaagaaaagtatttggct 2520 gctgctgctgcaagacatttggctactatgtgtagaatctacaacgactatggttccttg 2580 gctagagatactgctgaaagaaatgttaactccatgcactacccagaattcagacaaact 2640 actgctcaagctgaagatccaactatggctaaaaagaaggctttgttgtcattgggtgaa 2700 tacgaacacgatttcttgagagataccttggacagattggaaaaagctgttgctactcca 2760 ccaccaggtggtatggttgaatctaaaagattaagagtcgtcaggttgttcagatacttc 2820 tgtgatgttactgacttgtacgatcagttgtacgtcttgaaggatttgtcctcttcattg 2880 agaacctaa 2889 SEQIDNO:106 MLEGIGIGSSPQSLLDSAKDLIAEACSRTDPFYGLSTASCQTYDTAWVAMVVKRLESGED 60 AWAFPQSFRYILEAQTSGGGWGDPKASKTVGILDTAAALLALYRHLDRPLQITEVTRMDV 120 ESRIEKASTSLVSQLQQWDDLVESNHIGVELILPSLLEQLRQINPVLHSTRFKAEQDLTR 180 MHEEKLRHFDVSSLYSSRPSSALHSLEAFLGKLDFDRVGHHLYHGSMMASPSSTAAYLIG 240 ASTYDSTAEAYLSHILKCTAKGSPGGIPGTFPITNFEYSWITATLLRDCFAYEDLAGPSL 300 DCIGQTLEEALQAGKGVIGFAPRTADVDDTAKGLLALTSMRRYGHADPKPMIKVFEREDH 360 FTTFGSERDPSFTSNCHVLLSLLAQESDLPLYRAQIYKATKFLCDFLFYRDGPLKDKWHM 420 TSSYPSMLLVEAFSELLRLQDEQKFEQLLTSDEQHRVFIVLFQTCLRTLLVQSEDGSWSG 480 CTEQTSHAVCTLARAWRLNLFIDLRPDLQVAIQAGIQYLDRPEAQMGQNWTSKTVYSVDL 540 VGKAYILAARKMAQDLSDRTPFGPKREDFMSLKKFTTYLETSKRLPLLQATPPWQIIASL 600 TESALFLPLLRKEKEAIFPRDGTMLTPDDYLDIIPYTWVICGNRIDVHTSPSLALDMMLL 660 SMYGYQNDEFFETHAMAGHYQSGSDLKRLVDDVLQQNIPKCAEPSNGSSKHDTGNQSRTA 720 QEAAISLPEMSAGLNRFISYILKHPLVAQAHPNSKSELHRELQAFLHAHSDQSDENRRFA 780 AQEEKDELQSPSQTLFQYVRSTGGDHVACAYSLSFMLCIISSSLCDGGEVFQTAEEKYLA 840 AAAARHLATMCRIYNDYGSLARDTAERNVNSMHYPEFRQTTAQAEDPTMAKKKALLSLGE 900 YEHDFLRDTLDRLEKAVATPPPGGMVESKRLRVVRLFRYFCDVTDLYDQLYVLKDLSSSL 960 RT 962 SEQIDNO:107 atgtacgagaggtacttgttgttgttgcatatcttgactcacaagtccggtaagattgaa 60 aatggtactccaaagtacttgaaaaccggtgatgatttggtttctgctgctaagtctttg 120 ttggatagagctttcaagtcccatcattcttactacggtttgtgttctacctcttgccaa 180 gtttatgatactgcttgggttgccatgattagaaagactactgaaaatgtcaagcactgg 240 ttgttcccagaatgtttccattacttgttgaaaacccaagctgctgatggttcttggggt 300 gctttgccaactactcaaactgctggtattttggatactgcttctgctgttttggctttg 360 ttgtctcatgttagaaagccattgcaaatcttggatgtttccccagacgaaattggtcca 420 agaattgaacatggtgttgcctcattgaaaagacaattggctgtttggaaggacgtcgaa 480 gaaactaatcatatcggtgttgaattgatcgttccagccttgttgtctaccttggaaaaa 540 gaattgggtgagtcctcttttgaattcccatgtaagggtatcttggagaagatgtacgaa 600 gaaaagttgggtaacttcgacttgaagaaggtttacggtaaaccatcctctttgttgcat 660 tctttggaagctttcttgggtcaaatcgatttcgatagattgtcccatcacttgtacaga 720 ggttctatgatggcttctccatcttctactgctgcttatttgattggtgctactaagtgg 780 gatgatgaagctgaagattacttgagacacatcgttagaaatggtgctggtcatggtgat 840 ggtggtatttctggtacttttccaactacccatttcgaatgctcttggattttggctact 900 ttgttgcaaggtggtttcaccatgaagcaaattgattctaatggtttgagaggtttggct 960 accattttggctgatgctttgagagatgagaatggtgttattggttttgctccaagaact 1020 gccgatgttgatgatactgctaaagctttgttggccttgtccttgatcaatcaaccagtt 1080 tctccagacatcatgatcaaggtttttgaaggtaaggatcacttcactaccttcggttct 1140 gaaagagatccatctttgacttccaacttgcatgttttgttgtgcttgttgaagcagcca 1200 aacgtttctcaataccatccacaaattctaaagaccaccttgttcacttgtagatggtgg 1260 tggggttctgatcattgtgttaaggataagtggaacttgtctcacttgtacccaactatg 1320 ttgttggttgaagctttcactgaagtcttgcatttgattgatgctggtgagttgtcatcc 1380 ttgttcgataagtctttgaagtgcaagatcggcttgtctattttccaagctgttttgaga 1440 atcatcttgacccaagataatgacggttcttggagagcttatagagaacaaacttgctac 1500 gctatcttggctttggttcaagctagacatgtttgtttcttcacccacatggttgataga 1560 ttgcagtcttgtattgatagaggtgtctcttggttgaagtcctgtagatttcattcccaa 1620 gatttgacttggacttctaagactgcttacgaagttggttttgttgctgaagcttacaaa 1680 ttggctgctttacaatctgcctctttggaagttccagctgctactattggtcattctgtt 1740 acttcagctgttccatcttctgatttggagaagtacatgagattggttagaaagaccgct 1800 ttgttctctccattggatgaatggggtttgagagcttctgttatcgaatcttctttcttc 1860 gtgccattattgcaagcccaaagagttgaaatctacccaagagataacatcaagatcgat 1920 gaggacaagtatttgagcattattccattcacttgggtcggttgtaacaacagatctaga 1980 acttttgcttccaacagatggttgtacgacatgatgtatttgtccttgttgggttaccaa 2040 accgatgagtatatggaagctgttgctggtccagttttttccgatgtttctttgttgaga 2100 ttggccatcgataaggttattgataacaccagagttaacttggctggtacaaatggtact 2160 gttcataatggtaacggtcaccaacatgaatccccaaacattagacaagttgaagatacc 2220 ttgaccagattcgctaactctgttttgaaccacaaggatgtcttgaactcctcatcttct 2280 gatcaagacactttgagaagagaattcagagcttttatgcatgctcataccacccaaatc 2340 gaagataactctagattctctaagcaagcctctggtgatgttttttcatctccagaacaa 2400 tcctacttccaatgggttaattctactggtggttctcatgttgcttgtgcttactctttt 2460 gctttctctaactgtttgatgtccgctaatttgccacaaggtaaagaagcttttccatct 2520 gctacacagaagtacttgatctcttctgttatgagacatgctaccaacatgtgcagaatg 2580 tacaatgatttcggttccattgccagagataacgttgaaagaaacgttaactctatgcac 2640 ttcccagaattcgctttgtgtaagggtatttcccaaaccatcgatgacagaaagaagaga 2700 ttgtcccaaattgccatgtacgaacaaggttgtttggatagagcattggaagctttggaa 2760 agacaatctagagatgatgccggtgattctgctggttctaaagatgttagaaagatcaag 2820 atcgtcaagttgttctgtgaagttaccgacttgtatgatcagttgtacgttatcaaggac 2880 ttgtcctcttcaatgaagtaa 2901 SEQIDNO:108 MYERYLLLLHILTHKSGKIENGTPKYLKTGDDLVSAAKSLLDRAFKSHHSYYGLCSTSCQ 60 VYDTAWVAMIRKTTENVKHWLFPECFHYLLKTQAADGSWGALPTTQTAGILDTASAVLAL 120 LSHVRKPLQILDVSPDEIGPRIEHGVASLKRQLAVWKDVEETNHIGVELIVPALLSTLEK 180 ELGESSFEFPCKGILEKMYEEKLGNFDLKKVYGKPSSLLHSLEAFLGQIDFDRLSHHLYR 240 GSMMASPSSTAAYLIGATKWDDEAEDYLRHIVRNGAGHGDGGISGTFPTTHFECSWILAT 300 LLQGGFTMKQIDSNGLRGLATILADALRDENGVIGFAPRTADVDDTAKALLALSLINQPV 360 SPDIMIKVFEGKDHFTTFGSERDPSLTSNLHVLLCLLKQPNVSQYHPQILKTTLFTCRWW 420 WGSDHCVKDKWNLSHLYPTMLLVEAFTEVLHLIDAGELSSLFDKSLKCKIGLSIFQAVLR 480 IILTQDNDGSWRAYREQTCYAILALVQARHVCFFTHMVDRLQSCIDRGVSWLKSCRFHSQ 540 DLTWTSKTAYEVGFVAEAYKLAALQSASLEVPAATIGHSVTSAVPSSDLEKYMRLVRKTA 600 LFSPLDEWGLRASVIESSFFVPLLQAQRVEIYPRDNIKIDEDKYLSIIPFTWVGCNNRSR 660 TFASNRWLYDMMYLSLLGYQTDEYMEAVAGPVFSDVSLLRLAIDKVIDNTRVNLAGTNGT 720 VHNGNGHQHESPNIRQVEDTLTRFANSVLNHKDVLNSSSSDQDTLRREFRAFMHAHTTQI 780 EDNSRFSKQASGDVFSSPEQSYFQWVNSTGGSHVACAYSFAFSNCLMSANLPQGKEAFPS 840 ATQKYLISSVMRHATNMCRMYNDFGSIARDNVERNVNSMHFPEFALCKGISQTIDDRKKR 900 LSQIAMYEQGCLDRALEALERQSRDDAGDSAGSKDVRKIKIVKLFCEVTDLYDQLYVIKD 960 LSSSMK 966 SEQIDNO:109 atgaagactgtattgcaaccagataagcactcccacaagttgattttgtcatctcaacaa 60 ccagttccaactccatctcatccacaagatgttttggttaaggttcatgctacttgtcca 120 tgtaagggtgaattggattgggctttgtgggctccagaattcattggtgataagattcca 180 attccaggtcaagatttggctggtactgttgtttctgctccagaaaattctggtttcaag 240 ccagatgatgaagtttacgctagaattgaagctaatagaccaggtgctgctgctgaatat 300 gttttggctagagtttctgaattggccatcagaccaaagaatttgacttgggctgaaact 360 gctgcttctccaatttctgctttgactgcttatcaaggtttgttcactagaggtggttta 420 gatccaaaagctttggctggtgatgaagctgctagagaaaaaaatggtaaggtcagagtt 480 ttgatcaacggttctgctggtggtgttggttcttgggctgttcaattggctagattggct 540 ggtgttaagactattgccggtgttgttggtactcaaaacatcgattttgtcagacaattg 600 ggtgctaccgaaaccattgattacaaaaagcaatccattggtgaatgggctactcaagat 660 ccatcttctagacaattcgatttggttttcgattgcatcggtttgccatctttgtctcaa 720 acttggtatgctgttagagaaggtggtactttggtttctgtttgtgctccaccagaacaa 780 aacagaccagaagatgttaagaaagaagtcaactccatcttcttcgttatcgatccagtt 840 ggtaaggatttggaagttatcaccaagttgttggaagctggtcaaatcaagccacatatc 900 gattctgttgttggtttggatgatttcgaagaagcttgggaaaaagtcgaatctggtaga 960 actaagggtaaggttgttgttatggttatgaaggacgagtaa 1002 SEQIDNO:110 MKTVLQPDKHSHKLILSSQQPVPTPSHPQDVLVKVHATCPCKGELDWALWAPEFIGDKIP 60 IPGQDLAGTVVSAPENSGFKPDDEVYARIEANRPGAAAEYVLARVSELAIRPKNLTWAET 120 AASPISALTAYQGLFTRGGLDPKALAGDEAAREKNGKVRVLINGSAGGVGSWAVQLARLA 180 GVKTIAGVVGTQNIDFVRQLGATETIDYKKQSIGEWATQDPSSRQFDLVFDCIGLPSLSQ 240 TWYAVREGGTLVSVCAPPEQNRPEDVKKEVNSIFFVIDPVGKDLEVITKLLEAGQIKPHI 300 DSVVGLDDFEEAWEKVESGRTKGKVVVMVMKDE 333 SEQIDNO:111 atgggtagattcgaaggtaaggttgctgttgttactggtgctggtgctggtattggtaaa 60 gcttgtgctttggctattgctagagaaggtggtagagttgttgttgctgatattgatggt 120 tctgctgctattgcttgtactgctcaaattgctgctgaagctggtcatgctttggcttta 180 gctattgatattgctgatgctcaagctgttgctgctttgtttgaaactgctgaaagacat 240 tttggtggtgttgatttgttggttaacaacgcttctgctatgcatttgactccaagagat 300 agagccattttggaattggaattggctgtttgggatcaaactatggctagaaatttgagg 360 ggtactttgttgtgttgcagacaagctattccaagaatgattgctagaggtggtggtgct 420 atagttaacatgtcatcttgtcaaggtttgtctggtgatactgctttgacttcttatgct 480 gcttctaaggctgctatgaacatgttgtcatcttcattggctactcaatacggtcatgct 540 caaattagatgtaatgctgttgctccaggtttgatcatgactgaaagattgagaatgcaa 600 acccatttgagaaggcaccaattattgccaagagttggtagaccaagaacttggccaaga 660 tggtggagatcttgttctccaactatgttgagatcttctactggtcaagttgtctgtatt 720 gatggtggtatgttggctcatgttccaacttatgctgatggtggtaattctagagctgct 780 agaccagctggtgaaacagctgaagctgatgctgctccaagatgttaa 828 SEQIDNO:112 MGRFEGKVAVVTGAGAGIGKACALAIAREGGRVVVADIDGSAAIACTAQIAAEAGHALAL 60 AIDIADAQAVAALFETAERHFGGVDLLVNNASAMHLTPRDRAILELELAVWDQTMARNLR 120 GTLLCCRQAIPRMIARGGGAIVNMSSCQGLSGDTALTSYAASKAAMNMLSSSLATQYGHA 180 QIRCNAVAPGLIMTERLRMQTHLRRHQLLPRVGRPRTWPRWWRSCSPTMLRSSTGQVVCI 240 DGGMLAHVPTYADGGNSRAARPAGETAEADAAPRC 275 SEQIDNO:113 atgtccttcccagatgaacaaaaggttgatttccaaaccttccagaacgttatcaacaat 60 caattgtctccaacctccgaatccagacatggtatttgtccatctactgaagaatccttg 120 tgggaatctccagtttctactcaagatgatgttgatagagctgtttctgctgctaaagct 180 gcttatccagcttggagaaaattgtcttgggacgaaagagcttcttacttggttaagttt 240 gctgatgctattgaagcccacaagcaagaattcattgatttgttgggtagagaagctggt 300 aaaccaccacaagctggtggttttgaattgatgttggttatggaacacgttagggaaact 360 ccaaagttgagaattggtgaagttaagccagaagataacgaagatagaaccgctgttgtt 420 agatacgttccaattggtgttggtgttggtatagttccatggaattttccaatgttgttg 480 ggtattggtaaagcttacccagctatgttggctggtaatacttttatttggaagccatct 540 ccatacaccccatactctgctttgaaattggctgaaattggtgctaaagttttgccacca 600 ggtgttttacaagctttgtctggtggtgatgatttgggtccaatgttgactgctcatcca 660 gatgttgctaaggtttcttttactggttctactgaaaccggtaaaaagattatggctgct 720 tgtgctgctactttgaagagagttactttggaattgggtggtaatgatgctgctatcgtt 780 tgtgaagatgttgatattccaggtgttgctggtaaggttgcttttttggcttatgttcat 840 tctggtcagatctgcatgaacatcaagagaatctacgttcacgaatccatctacgacaag 900 ttcgtttccgaagttatcaagttcttgcatgctttgaaaaccggtgatttctctgatcca 960 gaagctttttttggtccaatccaaaacaagatgcagtacgaaaaattgcagaggttgtac 1020 gaacaaatcgataagcaaggttggaagtgtgcttttggttctgcttctccagctacttct 1080 gaaaaaggttattttgttccaccagtcttggttgataatccaccagaagattctgaaatc 1140 gtccaaatggaaccatttggtccaatagttccagttatgaagtggcaatctgaagatgat 1200 gttattgctagagctaacgcttctgattatggtttgggtgcttctgtttggtctaaagat 1260 gttgctagagcaagaagaatggctgaattattggaagctggttctgtttgggttaacacc 1320 cattttgaagttgctccaaatgttccttttggtggtcataagcaatctggtattggtatg 1380 gattggggtgaagttggtttgaaaggttggtgtaatccacaagcttattgggtcaaacat 1440 tccggttaa 1449 SEQIDNO:114 MSFPDEQKVDFQTFQNVINNQLSPTSESRHGICPSTEESLWESPVSTQDDVDRAVSAAKA 60 AYPAWRKLSWDERASYLVKFADAIEAHKQEFIDLLGREAGKPPQAGGFELMLVMEHVRET 120 PKLRIGEVKPEDNEDRTAVVRYVPIGVGVGIVPWNFPMLLGIGKAYPAMLAGNTFIWKPS 180 PYTPYSALKLAEIGAKVLPPGVLQALSGGDDLGPMLTAHPDVAKVSFTGSTETGKKIMAA 240 CAATLKRVILELGGNDAAIVCEDVDIPGVAGKVAFLAYVHSGQICMNIKRIYVHESIYDK 300 FVSEVIKFLHALKTGDFSDPEAFFGPIQNKMQYEKLQRLYEQIDKQGWKCAFGSASPATS 360 EKGYFVPPVLVDNPPEDSEIVQMEPFGPIVPVMKWQSEDDVIARANASDYGLGASVWSKD 420 VARARRMAELLEAGSVWVNTHFEVAPNVPFGGHKQSGIGMDWGEVGLKGWCNPQAYWVKH 480 SG 482 SEQIDNO:115 atgggtagattcgaaggtaaagttgctgtcgtcactggtgctggtgccggtattggtaag 60 gcttgtgccttggctattgctagagaaggtggtcgtgttgtcgtcgccgacatcgatggt 120 tccgctgctatcgcttgtactgctcaaatcgctgctgaagctggtcatgctttggctttg 180 gctatcgatatcgctgatgctcaagccgtcgccgccttattcgaaaccgccgaaagacat 240 ttcggtggtgttgacttgttggttaataacgcttccgctatgcacttgactcctagagac 300 agagctattttagaattggaattggctgtttgggatcaaaccatggctaccaacttgaga 360 ggtactttgttgtgctgtcgtcaagccatccctcgtatgattgctagaggtggtggtgct 420 atcgttaacatgtcttcttgtcaaggtttatctggtgacaccgctttgacttcctacgct 480 gcttctaaggccgccatgaacatgttgtcctcttctttggccacccaatatggtcacgcc 540 caaatcagatgtaacgccgttgctccaggtttaatcatgactgaaagattgttggctaaa 600 ttggatgcttgtatgcaaactcatttgagaagacaccaattgttgccaagagtcggtaga 660 cctgaagacgttgctgccttggttgcttttttgttatctgacgacgctgctttcatcact 720 ggtcaagttgtctgtatcgatggtggtatgttggctcacgttccaacctacgctgacggt 780 ggtaactctcgtgctgccagaccagctggtgaaactgctgaagccgatgctgctccaaga 840 tgctaa 846 SEQIDNO:116 MGRFEGKVAVVTGAGAGIGKACALAIAREGGRVVVADIDGSAAIACTAQIAAEAGHALAL 60 AIDIADAQAVAALFETAERHFGGVDLLVNNASAMHLTPRDRAILELALAVWDQTMATNLR 120 GTLLCCRQAIPRMIARGGGAIVNMSSCQGLSGDTALTSYAASKAAMNMLSSSLATQYGHA 180 QIRCNAVAPGLIMTERLLAKLDACMQTHLRRHQLLPRVGRPEDVAALVAFLLSDDAAFIT 240 GQVVCIDGGMLAHVPTYADGGNSRAARPAGETAEADAAPRC 281 SEQIDNO:117 atgagagttgttatcgatcaagatttgtgtggtactactggtcaatgtgtcttgactttg 60 ccaggtacttttagacaaagagaaccagacggtgtcgccgaagtctgtgttgctactgtc 120 ccacaagctttacacgctgctgctagattggctgcttcccaatgtcctgttgctgccatt 180 cgtgtcatcgagtctgacgctggtgaaagagcctctgctgatccagctccatccccagct 240 caagccgaaagacatgctgctaaggatcaaagaaatccaggtggtagattcgaaggtaag 300 gttgctgttgtcaccggtgctggtgctggtattggtaaagcttgtgctttagccattgct 360 agagaaggtggtagagttgttgtcgctgatatcgacggttctgctgccgtcgcctgtact 420 gcccaaatcgccgccgaggctggtcatgctttggctttggccatggatattgctgatgcc 480 caagccgttgctgctttgttcgaaactgctgaaagacactttggtggtgttgatttgttg 540 gtcaacaacgcttctgctatgcacttgaccccaagagatagaactattttggacttggac 600 ttggctgtctgggaccaaaccatggctactaatttgcgtggtaccttgttgtgttgtaga 660 caagctatcccacgtatgatcgcccgtggtggtggtgctatcgtcaacatgtcttcttgt 720 caaggtttatctggtgacaccgctcaaacttcttacgctgcctctaaggctgctatgaac 780 atgttgtccgcttctttggctacccaatacggtcacgctcaaattcgttgtaacgctgtc 840 gctccaggtttgattatgactgaaagattattagctaagttagatgaatgtatgcaaaga 900 cacttatccagacaccaattgttgcaacgtgtcggtagaccagaagatgttgctgccttg 960 gtcgcttttttattatctgacgacgctgctttcattactggtcaagtcttgtgtattgat 1020 ggtggtatgttggctcacgttccaacctacgctgacggtggtaactctagagctgctaga 1080 ccagccggtgatactgccaaggccgctgctggtccaagatgttaa 1125 SEQIDNO:118 MRVVIDQDLCGTTGQCVLTLPGTFRQREPDGVAEVCVATVPQALHAAARLAASQCPVAAI 60 RVIESDAGERASADPAPSPAQAERHAAKDQRNPGGRFEGKVAVVTGAGAGIGKACALAIA 120 REGGRVVVADIDGSAAVACTAQIAAEAGHALALAMDIADAQAVAALFETAERHFGGVDLL 180 VNNASAMHLTPRDRTILDLDLAVWDQTMATNLRGTLLCCRQAIPRMIARGGGAIVNMSSC 240 QGLSGDTAQTSYAASKAAMNMLSASLATQYGHAQIRCNAVAPGLIMTERLLAKLDECMQR 300 HLSRHQLLQRVGRPEDVAALVAFLLSDDAAFITGQVLCIDGGMLAHVPTYADGGNSRAAR 360 PAGDTAKAAAGPRC 374 SEQIDNO:119 atggacgctgtcactggtttgttgactgtcccagctactgctatcaccatcggtggtacc 60 gctgttgctttggctgtcgccttgatcttttggtacttaaaatccgatatgttgttgaat 120 ccattgaacagaagacatagattgagacatgacatcccagttgttccaggtgccttccca 180 ttggttggtcacttgcctgctgttgtttgcgatttgcctagattattgagaagagctgaa 240 cgtaccttgggttctcacttctggttagatttcggtccagctggtcatttgatgacttct 300 ttggacccagatgctttggctttgttgagacacaaggacgtctcttccggtttaattgaa 360 gatattgctccagaattattcggtggtactttggtcgctcaagacggtattgctcacaga 420 caagccagagacgctattcaagctgccttgttgcctaagggtttaactttggctggtatc 480 ggtgaattgttcgccccagttattagagccagagtccaaagatggagagaaagaggtgat 540 gtcactatcttgagagaaaccggtgatttgatgttaaagttgattttctccttgatgggt 600 atccctgctcaagatttgcctggttggcacagaaagtaccgtcaattattgcaattgatc 660 gtcgctccacctgtcgacttgccaggtttgccattgagaagaggtagagccgctagagac 720 tggatcgacgccagattgagagaatttgtcagagctgctcgtgagcacgcctctcgtacc 780 ggtttaatcaatgatatggtttctgctttcgacagatccgacgacgccttgtctgacgat 840 gttttggtcgctaacatcagattgttgttgttaggtggtcacgacaccaccgcttccact 900 atggcttggatggttattgaattggctcgtcaaccaggtttgtgggatgctttagttgaa 960 gaagctcaaagagttggtgctgttccaactcgtcatgctgacttggctcaatgtccagtt 1020 gccgaagccttattcagagaaactttaagagttcacccagccactccattattggtcaga 1080 agagctttgagagaattgagaatcggtcaacaacgtatcccaaccggtactgacttgtgt 1140 attccattgttgcacttctccacctccgctttgttgcatgaagctccagatcaatttaga 1200 ttggctagatggttacaaagaaccgaaccaatcagaccagttgatatgttacaattcggt 1260 actggtccacacttttgtatgggttaccacttagtttggttggaattggttcaattctgt 1320 attgctttggctttgaccatgcacgaagctggtgttagacctagattgttatccggtgtt 1380 gaaaagggtagaagatattacccaaccgcccatccatccatgaccattagaattggtttt 1440 tcttaa 1446 SEQIDNO:120 MDAVTGLLTVPATAITIGGTAVALAVALIFWYLKSDMLLNPLNRRHRLRHDIPVVPGAFP 60 LVGHLPAVVCDLPRLLRRAERTLGSHFWLDFGPAGHLMTSLDPDALALLRHKDVSSGLIE 120 DIAPELFGGTLVAQDGIAHRQARDAIQAALLPKGLTLAGIGELFAPVIRARVQRWRERGD 180 VTILRETGDLMLKLIFSLMGIPAQDLPGWHRKYRQLLQLIVAPPVDLPGLPLRRGRAARD 240 WIDARLREFVRAAREHASRTGLINDMVSAFDRSDDALSDDVLVANIRLLLLGGHDTTAST 300 MAWMVIELARQPGLWDALVEEAQRVGAVPTRHADLAQCPVAEALFRETLRVHPATPLLVR 360 RALRELRIGQQRIPTGIDLCIPLLHFSTSALLHEAPDQFRLARWLQRTEPIRPVDMLQFG 420 TGPHFCMGYHLVWLELVQFCIALALTMHEAGVRPRLLSGVEKGRRYYPTAHPSMTIRIGF 480 S 481 SEQIDNO:121 atgttgttgaatccattgaacagaagacatagattgagacatgacatcccagttgttcca 60 ggtgccttcccattggttggtcacttgcctgctgttgtttgcgatttgcctagattattg 120 agaagagctgaacgtaccttgggttctcacttctggttagatttcggtccagctggtcat 180 ttgatgacttctttggacccagatgctttggctttgttgagacacaaggacgtctcttcc 240 ggtttaattgaagatattgctccagaattattcggtggtactttggtcgctcaagacggt 300 attgctcacagacaagccagagacgctattcaagctgccttgttgcctaagggtttaact 360 ttggctggtatcggtgaattgttcgccccagttattagagccagagtccaaagatggaga 420 gaaagaggtgatgtcactatcttgagagaaaccggtgatttgatgttaaagttgattttc 480 tccttgatgggtatccctgctcaagatttgcctggttggcacagaaagtaccgtcaatta 540 ttgcaattgatcgtcgctccacctgtcgacttgccaggtttgccattgagaagaggtaga 600 gccgctagagactggatcgacgccagattgagagaatttgtcagagctgctcgtgagcac 660 gcctctcgtaccggtttaatcaatgatatggtttctgctttcgacagatccgacgacgcc 720 ttgtctgacgatgttttggtcgctaacatcagattgttgttgttaggtggtcacgacacc 780 accgcttccactatggcttggatggttattgaattggctcgtcaaccaggtttgtgggat 840 gctttagttgaagaagctcaaagagttggtgctgttccaactcgtcatgctgacttggct 900 caatgtccagttgccgaagccttattcagagaaactttaagagttcacccagccactcca 960 ttattggtcagaagagctttgagagaattgagaatcggtcaacaacgtatcccaaccggt 1020 actgacttgtgtattccattgttgcacttctccacctccgctttgttgcatgaagctcca 1080 gatcaatttagattggctagatggttacaaagaaccgaaccaatcagaccagttgatatg 1140 ttacaattcggtactggtccacacttttgtatgggttaccacttagtttggttggaattg 1200 gttcaattctgtattgctttggctttgaccatgcacgaagctggtgttagacctagattg 1260 ttatccggtgttgaaaagggtagaagatattacccaaccgcccatccatccatgaccatt 1320 agaattggtttttcttaa 1338 SEQIDNO:122 MLLNPLNRRHRLRHDIPVVPGAFPLVGHLPAVVCDLPRLLRRAERTLGSHFWLDFGPAGH 60 LMTSLDPDALALLRHKDVSSGLIEDIAPELFGGTLVAQDGIAHRQARDAIQAALLPKGLT 120 LAGIGELFAPVIRARVQRWRERGDVTILRETGDLMLKLIFSLMGIPAQDLPGWHRKYRQL 180 LQLIVAPPVDLPGLPLRRGRAARDWIDARLREFVRAAREHASRTGLINDMVSAFDRSDDA 240 LSDDVLVANIRLLLLGGHDTTASTMAWMVIELARQPGLWDALVEEAQRVGAVPTRHADLA 300 QCPVAEALFRETLRVHPATPLLVRRALRELRIGQQRIPTGTDLCIPLLHFSTSALLHEAP 360 DQFRLARWLQRTEPIRPVDMLQFGTGPHFCMGYHLVWLELVQFCIALALTMHEAGVRPRL 420 LSGVEKGRRYYPTAHPSMTIRIGFS 445 SEQIDNO:123 atggatgctgtcaccggtttgttaaccgttccagctaccgctattaccatcggtggtacc 60 gctgtcgccttagctgttgctttgattttctggtacttaaagtcttctgaacaacaacct 120 ttgccaaccttgccaatgtggagagttgaccacattgaaccttctccagaaatgttggct 180 ttgagagctaatggtcctatccatcgtgttcgtttcccatctggtcacgaaggttggtgg 240 gtcaccggttatgacgaagctaaggctgttttgtccgatgccgccttccgtcctgctggt 300 atgcctccagctgctttcactccagactctgtcattttgggttctccaggttggttagtc 360 tctcacgaaggtagagaacatgctagattgcgtgctattgttgctccagctttctctgat 420 agaagagttaaattgttggtccaacaagtcgaagccattgctgcccacttgttcgagact 480 ttagctgcccaacctcaacctgccgatttgagaagacacttgtctttccctttaccagcc 540 atggttatttctgccttaatgggtgtcttatacgaggaccacgctttctttgctggtttg 600 tctgacgaagttatgactcaccaacatgaatccggtccacgttctgcttctagattggcc 660 tgggaggaattgagagcctacattagaggtaagatgagagacaagagacaagacccagac 720 gataacttgttaactgatttgttggctgctgtcgatcaaggtaaggcttccgaagaagaa 780 gctgttggtttggccgctggtatgttggttgctggtcatgaatctactgttgcccaaatc 840 gaatttggtttgttggccatgttcagacacccacaacaaagagaaagattagttggtgat 900 ccatctttggttgacaaggctgttgaggaaattttgagaatgtatccaccaggtgctggt 960 tgggatggtatcatgcgttacccaagaactgatgttactatcgctggtgaacacattcca 1020 gccgaatccaaggttttggtcggtttgccagctacctccttcgatccacaccactttgac 1080 gatccagaaatcttcgacatcgaaagacaagaaaaaccacacttagccttttcctacggt 1140 cctcacgcttgtatcggtgttgctttggctagattggagttgaaggttgtcttcggttct 1200 attttccaaagattgcctgctttacgtttagccgttgctccagaacaattgaagttgaga 1260 aaggaaatcatcaccggtggttttgaacaattcccagttttgtggtaa 1308 SEQIDNO:124 MDAVTGLLTVPATAITIGGTAVALAVALIFWYLKSSEQQPLPTLPMWRVDHIEPSPEMLA 60 LRANGPIHRVRFPSGHEGWWVTGYDEAKAVLSDAAFRPAGMPPAAFTPDSVILGSPGWLV 120 SHEGREHARLRAIVAPAFSDRRVKLLVQQVEAIAAHLFETLAAQPQPADLRRHLSFPLPA 180 MVISALMGVLYEDHAFFAGLSDEVMTHQHESGPRSASRLAWEELRAYIRGKMRDKRQDPD 240 DNLLTDLLAAVDQGKASEEEAVGLAAGMLVAGHESTVAQIEFGLLAMFRHPQQRERLVGD 300 PSLVDKAVEEILRMYPPGAGWDGIMRYPRTDVTIAGEHIPAESKVLVGLPATSFDPHHFD 360 DPEIFDIERQEKPHLAFSYGPHACIGVALARLELKVVFGSIFQRLPALRLAVAPEQLKLR 420 KEIITGGFEQFPVLW 435 SEQIDNO:125 atggacgctgttaccggtttgttgactgttccagctactgctatcaccattggtggtact 60 gctgttgctttggctgtcgctttaatcttctggtatttaaagtccgacgttcaagaaacc 120 actgctgcttgcagagacgctttcgctgaattagcttccccagcttgtattcacgatcct 180 tacccattcatgagatggttgcgtgaacacgacccagttcacagagctgcctctggtttg 240 ttcttgttgtccagacatgctgatatcttttgggctttcaaggccaccggtgatgctttc 300 agaggtccagctccaggtgagttggctagatacttttctagagctgccacctctccatcc 360 ttgaacttgttggcctctactttggctatgaaggatccacctacccacaccagattgaga 420 agattgatttctagagacttcactatgggtcaaatcgacaacttgagaccatccattgcc 480 agaatcgttgccgctagattagatggtattactccagccttggaaagaggtgaagctgtc 540 gacttgcacagagaatttgctttggccttacctatgttggttttcgctgaattgtttggt 600 atgcctcaagatgatatgtttgagttagctgccggtatcggtactattttggaaggtttg 660 ggtccacatgcttctgatccacaattggctgctgccgacgctgcttctgctagagtccaa 720 gcttacttcggtgatttgatccaaagaaaacgtaccgatcctagaagagacatcgtctcc 780 atgttggttggtgctcacgatgacgatgccgatactttgtctgacgctgaattaatttct 840 atgttgtggggtatgttgttaggtggtttcgttaccactgctgcctccatcgatcatgct 900 gttttggctatgttggcttatccagaacaaagacattggttacaagctgacgctgctaga 960 gttagagcttttgttgaagaagttttaagatgtgacgctccagctatgttttcctccatt 1020 ccaagaattgctcaaagagatatcgaattgggtggtgtcgtcattcctaagaacgctgac 1080 gttagagtcttaatcgcctccggtaacagagatccagacgcttttgctgatccagataga 1140 ttcgatccagctagattctatggtacctccccaggtatgtctactgacggtaaaattatg 1200 ttatctttcggtcatggtatccacttctgcttaggtgcccaattggccagagtccaattg 1260 gctgaatctttgcctagaattcaagctagatttccaactttggcttttgctggtcaacca 1320 accagagaaccatccgctttcttaagaactttccgtactttgccagtcagattgcatgcc 1380 caaggttcctaa 1392 SEQIDNO:126 MDAVTGLLTVPATAITIGGTAVALAVALIFWYLKSDVQETTAACRDAFAELASPACIHDP 60 YPFMRWLREHDPVHRAASGLFLLSRHADIFWAFKATGDAFRGPAPGELARYESRAATSPS 120 LNLLASTLAMKDPPTHTRLRRLISRDFTMGQIDNLRPSIARIVAARLDGITPALERGEAV 180 DLHREFALALPMLVFAELFGMPQDDMFELAAGIGTILEGLGPHASDPQLAAADAASARVQ 240 AYFGDLIQRKRTDPRRDIVSMLVGAHDDDADTLSDAELISMLWGMLLGGFVTTAASIDHA 300 VLAMLAYPEQRHWLQADAARVRAFVEEVLRCDAPAMFSSIPRIAQRDIELGGVVIPKNAD 360 VRVLIASGNRDPDAFADPDRFDPARFYGTSPGMSTDGKIMLSFGHGIHFCLGAQLARVQL 420 AESLPRIQARFPTLAFAGQPTREPSAFLRTFRTLPVRLHAQGS 463 SEQIDNO:127 atgtctgaacaacaacctttgccaaccttgccaatgtggagagttgaccacattgaacct 60 tctccagaaatgttggctttgagagctaatggtcctatccatcgtgttcgtttcccatct 120 ggtcacgaaggttggtgggtcaccggttatgacgaagctaaggctgttttgtccgatgcc 180 gccttccgtcctgctggtatgcctccagctgctttcactccagactctgtcattttgggt 240 tctccaggttggttagtctctcacgaaggtagagaacatgctagattgcgtgctattgtt 300 gctccagctttctctgatagaagagttaaattgttggtccaacaagtcgaagccattgct 360 gcccacttgttcgagactttagctgcccaacctcaacctgccgatttgagaagacacttg 420 tctttccctttaccagccatggttatttctgccttaatgggtgtcttatacgaggaccac 480 gctttctttgctggtttgtctgacgaagttatgactcaccaacatgaatccggtccacgt 540 tctgcttctagattggcctgggaggaattgagagcctacattagaggtaagatgagagac 600 aagagacaagacccagacgataacttgttaactgatttgttggctgctgtcgatcaaggt 660 aaggcttccgaagaagaagctgttggtttggccgctggtatgttggttgctggtcatgaa 720 tctactgttgcccaaatcgaatttggtttgttggccatgttcagacacccacaacaaaga 780 gaaagattagttggtgatccatctttggttgacaaggctgttgaggaaattttgagaatg 840 tatccaccaggtgctggttgggatggtatcatgcgttacccaagaactgatgttactatc 900 gctggtgaacacattccagccgaatccaaggttttggtcggtttgccagctacctccttc 960 gatccacaccactttgacgatccagaaatcttcgacatcgaaagacaagaaaaaccacac 1020 ttagccttttcctacggtcctcacgcttgtatcggtgttgctttggctagattggagttg 1080 aaggttgtcttcggttctattttccaaagattgcctgctttacgtttagccgttgctcca 1140 gaacaattgaagttgagaaaggaaatcatcaccggtggttttgaacaattcccagttttg 1200 tggtaa 1206 SEQIDNO:128 MSEQQPLPTLPMWRVDHIEPSPEMLALRANGPIHRVRFPSGHEGWWVTGYDEAKAVLSDA 60 AFRPAGMPPAAFTPDSVILGSPGWLVSHEGREHARLRAIVAPAFSDRRVKLLVQQVEAIA 120 AHLFETLAAQPQPADLRRHLSFPLPAMVISALMGVLYEDHAFFAGLSDEVMTHQHESGPR 180 SASRLAWEELRAYIRGKMRDKRQDPDDNLLTDLLAAVDQGKASEEEAVGLAAGMLVAGHE 240 STVAQIEFGLLAMFRHPQQRERLVGDPSLVDKAVEEILRMYPPGAGWDGIMRYPRIDVTI 300 AGEHIPAESKVLVGLPATSFDPHHFDDPEIFDIERQEKPHLAFSYGPHACIGVALARLEL 360 KVVFGSIFQRLPALRLAVAPEQLKLRKEIITGGFEQFPVLW 401 SEQIDNO:129 atgttgtccagacatgctgatatcttttgggctttcaaggccaccggtgatgctttcaga 60 ggtccagctccaggtgagttggctagatacttttctagagctgccacctctccatccttg 120 aacttgttggcctctactttggctatgaaggatccacctacccacaccagattgagaaga 180 ttgatttctagagacttcactatgggtcaaatcgacaacttgagaccatccattgccaga 240 atcgttgccgctagattagatggtattactccagccttggaaagaggtgaagctgtcgac 300 ttgcacagagaatttgctttggccttacctatgttggttttcgctgaattgtttggtatg 360 cctcaagatgatatgtttgagttagctgccggtatcggtactattttggaaggtttgggt 420 ccacatgcttctgatccacaattggctgctgccgacgctgcttctgctagagtccaagct 480 tacttcggtgatttgatccaaagaaaacgtaccgatcctagaagagacatcgtctccatg 540 ttggttggtgctcacgatgacgatgccgatactttgtctgacgctgaattaatttctatg 600 ttgtggggtatgttgttaggtggtttcgttaccactgctgcctccatcgatcatgctgtt 660 ttggctattttggcttatccagaacaaagacattggttacaagctgacgctgctagagtt 720 agagcttttgttgaagaagttttaagatgtgacgctccagctatgttttcctccattcca 780 agaattgctcaaagagatatcgaattgggtggtgtcgtcattcctaagaacgctgacgtt 840 agagtcttaatcgcctccggtaacagagatccagacgcttttgctgatccagatagattc 900 gatccagctagattctatggtacctccccaggtatgtctactgacggtaaaattatgtta 960 tctttcggtcatggtatccacttctgcttaggtgcccaattggccagagtccaattggct 1020 gaatctttgcctagaattcaagctagatttccaactttggcttttgctggtcaaccaacc 1080 agagaaccatccgctttcttaagaactttccgtactttgccagtcagattgcatgcccaa 1140 ggttcctaa 1149 SEQIDNO:130 MLSRHADIFWAFKATGDAFRGPAPGELARYFSRAATSPSLNLLASTLAMKDPPTHTRLRR 60 LISRDFTMGQIDNLRPSIARIVAARLDGITPALERGEAVDLHREFALALPMLVFAELFGM 120 PQDDMFELAAGIGTILEGLGPHASDPQLAAADAASARVQAYFGDLIQRKRTDPRRDIVSM 180 LVGAHDDDADTLSDAELISMLWGMLLGGFVTTAASIDHAVLAMLAYPEQRHWLQADAARV 240 RAFVEEVLRCDAPAMFSSIPRIAQRDIELGGVVIPKNADVRVLIASGNRDPDAFADPDRF 300 DPARFYGTSPGMSTDGKIMLSFGHGIHFCLGAQLARVQLAESLPRIQARFPTLAFAGQPT 360 REPSAFLRTFRTLPVRLHAQGS 382 SEQIDNO:131 atgatccaaaccgaaagagccgttcaacaagttttggaatggggtagatctttgactggt 60 tttgctgatgaacatgctgttgaagctgttagaggtggtcagtacatcttgcaaagaatt 120 catccatctttgagaggtacatctgctagaactggtagagatccacaagacgaaactttg 180 atcgttaccttctatagagaattggccttgttgttttggttggatgattgcaatgatttg 240 ggcttgatttccccagaacaattggctgctgttgaacaagctttgggtcaaggtgttcca 300 tgtgctttgccaggttttgaaggttgtgctgttttgagagcttctttggctactttggct 360 tacgatagaagagattatgctcagttgttggatgataccagatgttattctgctgcttta 420 agagctggtcatgctcaagctgttgctgctgaaagatggtcttatgctgaatacttgcat 480 aacggtattgactccattgcttacgctaacgttttctgttgtttgtctttgttgtggggt 540 ttggatatggctactttgagagctagaccagcttttagacaagtcttgagattgatttcc 600 gccatcggtagattgcaaaatgacttgcatggttgcgataaggatagatctgctggtgaa 660 gctgataacgctgttattttgttgttgcaaagatacccagctatgccagttgttgaattc 720 ttgaatgatgaattggctggtcacaccagaatgttgcatagagttatggctgaagaaaga 780 tttccagctccatggggtccattgattgaagctatggctgctattagagttcagtactac 840 agaacttctacctccagatatagatccgatgctgtaagaggtggacaaagagcaccagct 900 taa 903 SEQIDNO:132 MIQTERAVQQVLEWGRSLTGFADEHAVEAVRGGQYILQRIHPSLRGTSARTGRDPQDETL 60 IVTFYRELALLFWLDDCNDLGLISPEQLAAVEQALGQGVPCALPGFEGCAVLRASLATLA 120 YDRRDYAQLLDDTRCYSAALRAGHAQAVAAERWSYAEYLHNGIDSIAYANVFCCLSLLWG 180 LDMATLRARPAFRQVLRLISAIGRLQNDLHGCDKDRSAGEADNAVILLLQRYPAMPVVEF 240 LNDELAGHTRMLHRVMAEERFPAPWGPLIEAMAAIRVQYYRTSTSRYRSDAVRGGQRAPA 300 SEQIDNO:133 atggctggtgattctcatgaaccatttgctactatagtcgagtctcctttgtcttacgtt 60 tcttccttgccatccaaacatttcagagttcaattattggaggccttgaacatctggtat 120 gaattgccacaaaacgaggtttccaagatcggtgatatcttgcagttgttgcataactcc 180 tcattgatcttggatgacttccaagatagatccccattgagaagaggtagaccagctgct 240 catgctttgtttggtgaagctcaagctattaactcttcctcttacggtttcattaaggct 300 gttgctttggctcaagaatccttcgatttggaatctactaaggctgttactaccgctatg 360 ttgagatcttttgaaggtcaagctgctgaattgcattggactcatacaaaaacttgccca 420 tccgttcaagaatacttggaaatggttaacttctcctccttgttgcatttggctccacaa 480 ttgatgcaagctaaaagaggttctgctactccagttgatcaaaggtctatggtttccttg 540 atgagattgctaggtcaattctaccaaatcagggacgactatatgaacttgacttctgct 600 cattacgaaaaggataagggtttctgcgaagatttggacgaaggtaaatattccttgcca 660 ttgattcatgctttggccgttaagccaagatctgttttgttggcttctgctttggctgct 720 tctggtgctccaggtggtttatctagacaacaaaaagtctgcatcttggaagaattggaa 780 aaggctagatctttggcttggacaaaagctactttgtgcgaattgcaagttgccatgtct 840 gaagaaattgcccaattggaagatagattcggtagaccaaacgagttgttgcaaaccttg 900 atttctaaggttgccattaagtaa 924 SEQIDNO:134 MAGDSHEPFATIVESPLSYVSSLPSKHFRVQLLEALNIWYELPQNEVSKIGDILQLLHNS 60 SLILDDFQDRSPLRRGRPAAHALFGEAQAINSSSYGFIKAVALAQESFDLESTKAVTTAM 120 LRSFEGQAAELHWTHTKTCPSVQEYLEMVNFSSLLHLAPQLMQAKRGSATPVDQRSMVSL 180 MRLLGQFYQIRDDYMNLTSAHYEKDKGFCEDLDEGKYSLPLIHALAVKPRSVLLASALAA 240 SGAPGGLSRQQKVCILEELEKARSLAWTKATLCELQVAMSEEIAQLEDRFGRPNELLQTL 300 ISKVAIK 307 SEQIDNO:135 atggctgctagattgttaagagttgcctctgctgcactaggtgatactgccggaagatgg 60 agactattagtaagaccaagagctggcgccggtggattaaggggctcaagaggtcctggt 120 ctaggaggcggtgccgtcgctacaagaaccctttccgtgagtggaagggcacaaagctct 180 tcagaggacaaaattactgttcactttatcaatagagatggtgagacattgaccactaag 240 ggcaaaatcggtgactccttattggatgtagtcgtgcagaacaacttagacattgatgga 300 ttcggtgcttgtgaaggcacactagcctgcagtacctgtcaccttatatttgagcaacat 360 atcttcgaaaagttggaagcaattactgatgaggaaaacgacatgttagatctagcttat 420 ggtttgacagacaggagcagattaggatgccagatatgtcttaccaaagccatggataat 480 atgactgttagagtaccagatgcagtctctgacgctagggaatcaatcgatatgggtatg 540 aactccagtaagattgagtaa 561 SEQIDNO:136 MAARLLRVASAALGDTAGRWRLLVRPRAGAGGLRGSRGPGLGGGAVATRTLSVSGRAQSS 60 SEDKITVHFINRDGETLITKGKIGDSLLDVVVQNNLDIDGFGACEGTLACSTCHLIFEQH 120 IFEKLEAITDEENDMLDLAYGLTDRSRLGCQICLTKAMDNMTVRVPDAVSDARESIDMGM 180 NSSKIE 186 SEQIDNO:137 atgcttttgaacacctttacccaaactgccagaagtgacaggtgtgctttctatggaaat 60 gtcgaagtgggcagagatgttacagtacaagaattaagggtctacaggttgaccgcagtt 120 gttctaagctatggtgccgaagatcaccaggcacttgatattccaggtgaagagttgcca 180 ggagttttttctgcaagagctttcgtaggctggtacaacggtttgccagaaaatagagaa 240 ttagcccctgacctatcatgcgatactgcagtcatattgggacaaggtaacgtggctttg 300 gacgttgccaggatacttttgaccccacctgaccacttagagaaaactgatattaccgaa 360 gcagctctaggcgcccttagacagtccagagtaaagacagtctggatagttggtaggaga 420 ggaccattgcaagtggcctttactatcaaagagcttagagagatgattcaacttcctggc 480 accaggcctatgttggacccagctgatttcttaggccttcaggatagaattagggaagcc 540 gcaagacctagaaagaggttgatggagttactattgagaacagctactgaaaaaccaggt 600 gttgaagaggccgcaagaagggctagtgctagcagagcttggggattaaggtttttcaga 660 agccctcaacaagtacttaggcttccagacggtagggcaagaagatcagcttggcagtcc 720 cctgaattggaaggcataggagaggcccatccaggtagcgcacactggggctgtggtgga 780 cctccatgcggtttagtactttcttcaatcggctataagtctaggcctattgatccaagc 840 gtgccttttgacccaaaattgggtgttgtaccaaatatggaaggaagagtcgttgatgtg 900 cctggtttatactgttccggctgggttaagagaggaccaacaggtgtaataaccactaca 960 atgactgatagttttctaaccggtcaaattttgctacaggaccttaaagctggccatttg 1020 ccttccggtccaaggcctggctcagccttcattaaggcactattagattctaggggtgtc 1080 tggccagtttcctttagtgactgggaaaaattggatgctgaggaagtgagcagaggccaa 1140 gcatctggaaagcctagagaaaaacttctagatcctcaagagatgctaagattgttaggt 1200 cactga 1206 SEQIDNO:138 MLLNTFTQTARSDRCAFYGNVEVGRDVTVQELRVYRLTAVVLSYGAEDHQALDIPGEELP 60 GVFSARAFVGWYNGLPENRELAPDLSCDTAVILGQGNVALDVARILLTPPDHLEKTDITE 120 AALGALRQSRVKTVWIVGRRGPLQVAFTIKELREMIQLPGTRPMLDPADFLGLQDRIREA 180 ARPRKRLMELLLRTATEKPGVEEAARRASASRAWGLRFFRSPQQVLRLPDGRARRSAWQS 240 PELEGIGEAHPGSAHWGCGGPPCGLVLSSIGYKSRPIDPSVPFDPKLGVVPNMEGRVVDV 300 PGLYCSGWVKRGPTGVITTTMTDSFLTGQILLQDLKAGHLPSGPRPGSAFIKALLDSRGV 360 WPVSFSDWEKLDAEEVSRGQASGKPREKLLDPQEMLRLLGH 401 SEQIDNO:139 atggtggacacaaacttattggcttctgttgccgtcgctctagtcgtcgttttcgttgct 60 tacaagtactttaatggtgggctggaagtccaatcatctaatgctggatctagtacacct 120 tttggtaatgcaaaggctgacgaagacggagattccaggaacttcgtggctttgatggaa 180 aaaaataataagaacgttattgttttctatggttcccaaacaggaacggccgaggatttg 240 gctagcaaattggccaaggagttaagctcaaagtatggtctaaggacaatgaccgccgat 300 cccgaaaattttgatttcgacaaatttgatacctttccagagagtcatctggctgttttt 360 atcacagccagttacggagatggcgaacctacagacaatgcacaggatttatattccttc 420 ttaggtaattcaccaagtttctcacaggatggtgaaacccttgagaaccttaattttgca 480 gtgttcggtttaggtaatgtactatatgaattctacaacaaggccggcagagatatgcac 540 aagtttctaactgatttaggcggtcactcaataggtccatacggggaaggtgatgactca 600 aaagggatgttagaggaagattacatggcatggaaagatgaatttctagctgccctagtt 660 acgaaatggggtttgaaggaaagagaagctgtctacgagccagccattagtgtgaaggat 720 attgaagaggatgctcaatcacatgacgtttacttgggtgaaccaaacctaaagcactta 780 caagctagcaaggcccgtgaagtccccaaagggccgtataatgctagcaatccaatgtta 840 gccaaggttacagcagctcaggagttgtttactaacactgatcgtcattgtattcatatg 900 gagtttgatactaccggcgcgaggtataccacgggcgatcacctggctttctggtgtcaa 960 aataacgaagaggaagttcagagattcgctaaggcattaggtataaccaacccgcagcaa 1020 ccaattgcaatatcagtgcttgacaagacttcaacagtaagaattcccagtccaactacc 1080 tatgagaccattataagacattttttagagatcaacggcccagtgagccgtcaagttctt 1140 agtagcattgcaccgttcgccccgagcgaggaagtcaagaaagctacgcaacagctaggc 1200 tctaacaaggaactgtttgctagtcatgttgccgcaaaaaagtttaacatagcaagattg 1260 ttgttgcatttatcaggcggccaaccttggaaaaacgtccccttttcattcatcattgaa 1320 accattccccatctacaacccaggtactactctatttcctcatcatcagtccaaagccct 1380 aatactatctctattactgctgtcgtggaaagacaaaagttagccggtgtagatcatgaa 1440 ttgagaggtgtagccacgaatcaaattttggccttgtccgaagcattgataggtagacct 1500 tcaagcacatacagactacagcagccccatgattttacaggttcattaaattcacaagat 1560 attagagtaccagtacatattagacatagcttatttaagctacctgccaaacccacagtt 1620 ccaataataatggtcggaccaggtaccggcgtcgcgccattcagaggttttgtgcatgaa 1680 agggcagctcaaaaggctgccggtaaggaagttggaaaagctctattgttcaccggatca 1740 agacatgcaaatgaggattttctatacagagacgaatggaaacaatttagtgattttttg 1800 gatttggaaacagctttttctagagattccaatactaaggtttatgtgcaacacaagctg 1860 aaagaaagagccaaggacgtgtttgctttgcttaatgaaggcgcggttttctatgtctgc 1920 ggtgacgcgggtggaatgtcacatgatgtgcatagcgccttgttggaaattgtagctcaa 1980 gagggtaacttgtctagcgaagatgcagataaatttgtcaggaaaatgagatcaagaaat 2040 aagtaccaagaggatgtatggtaa 2064 SEQIDNO:140 MVDTNLLASVAVALVVVFVAYKYFNGGLEVQSSNAGSSTPFGNAKADEDGDSRNFVALME 60 KNNKNVIVFYGSQTGTAEDLASKLAKELSSKYGLRTMTADPENFDFDKFDTFPESHLAVF 120 ITASYGDGEPTDNAQDLYSFLGNSPSFSQDGETLENLNFAVFGLGNVLYEFYNKAGRDMH 180 KFLTDLGGHSIGPYGEGDDSKGMLEEDYMAWKDEFLAALVTKWGLKEREAVYEPAISVKD 240 IEEDAQSHDVYLGEPNLKHLQASKAREVPKGPYNASNPMLAKVTAAQELFTNTDRHCIHM 300 EFDTTGARYTTGDHLAFWCQNNEEEVQRFAKALGITNPQQPIAISVLDKTSTVRIPSPIT 360 YETIIRHFLEINGPVSRQVLSSIAPFAPSEEVKKATQQLGSNKELFASHVAAKKFNIARL 420 LLHLSGGQPWKNVPFSFIIETIPHLQPRYYSISSSSVQSPNTISITAVVERQKLAGVDHE 480 LRGVATNQILALSEALIGRPSSTYRLQQPHDFTGSLNSQDIRVPVHIRHSLFKLPAKPTV 540 PIIMVGPGTGVAPFRGFVHERAAQKAAGKEVGKALLFTGSRHANEDFLYRDEWKQFSDFL 600 DLETAFSRDSNTKVYVQHKLKERAKDVFALLNEGAVFYVCGDAGGMSHDVHSALLEIVAQ 660 EGNLSSEDADKFVRKMRSRNKYQEDVW 687 SEQIDNO:141 atgtccatattcaacatgatcacttcttacgctggcagtcaattactgccattctatatt 60 gctatttttgtttttactctggttccttgggctatcaggttttcttggcttgaattgagg 120 aaggggtctgtagtccccttagcaaatccacccgatagtctttttggaacaggtaagaca 180 cgtagatcctttgtaaaattatctagggaaatattagctaaggctagatcattgtttccg 240 aacgaaccctttagattaatcactgactggggcgaggtattaatattacctcctgatttt 300 gctgacgaaatacgtaatgatccgaggctatcattcagtaaagctgctatgcaagataat 360 cacgccggtattccagggtttgagacagtcgctttggtgggacgtgaagaccaattaata 420 caaaaagtcgccagaaagcaattgactaagcatcttagcgcagtaattgaacctctgagt 480 agggaaagtaccctagctgtatctctaaattttggagaaacgacagaatggagagccatt 540 aggcttaagccagcaattcttgatattattgctaggatctcctcacgtatctatctagga 600 gatcaactatgcaggaatgaggcatggctaaagattactaagacttacacaacaaacttt 660 tacactgcctctaccaatcttagaatgttccccagaagtataagacctttagctcactgg 720 ttcttgccagaatgtagaaagcttcgtcaagagaggaaggatgcaattggtattataacg 780 ccactaatcgaaaggagaagagaattgcgtagagcagctattgcagctggacagccttta 840 ccagtttttcacgacgcaatcgattggtccgaacaagaggctgaagctgccggtacaggt 900 gcatcatttgaccctgtgatatttcaattaacattgtctttgttggctattcatacaacc 960 tatgacttattgcaacagaccatgatagacttgggtaggcaccctgaatatatagaacct 1020 ctgagacaagaagttgtgcaactgttgagagaagaaggttggaagaaaactactttattt 1080 aagatgaagttacttgattccgcaataaaggaaagtcaaagaatgaaaccaggatccatt 1140 gtcacgatgcgtcgttacgtgaccgaggacatcacactatcctctggtttaacgctaaaa 1200 aaaggcaccagattgaatgttgacaatcgtaggttggatgatcccaagatctatgacaat 1260 cctgaagtctataatccttatcgtttttatgatatgagatccgaagcaggtaaagatcat 1320 ggcgcccagctggttagtacaggctctaatcacatgggttttggccatgggcaacattca 1380 tgtccgggtagattttttgccgcaaatgagatcaaagtagccctatgtcatattttagtg 1440 aaatatgactggaaattatgcccagatacagaaaccaaacctgacactcgtgggatgata 1500 gctaagtctagcccagttactgacatccttattaagagaagagaatcagtagagttagat 1560 ttagaggcgatttaa 1575 SEQIDNO:142 MSIFNMITSYAGSQLLPFYIAIFVFTLVPWAIRFSWLELRKGSVVPLANPPDSLFGTGKT 60 RRSFVKLSREILAKARSLFPNEPFRLITDWGEVLILPPDFADEIRNDPRLSFSKAAMQDN 120 HAGIPGFETVALVGREDQLIQKVARKQLTKHLSAVIEPLSRESTLAVSLNFGETTEWRAI 180 RLKPAILDIIARISSRIYLGDQLCRNEAWLKITKTYTINFYTASTNLRMFPRSIRPLAHW 240 FLPECRKLRQERKDAIGIITPLIERRRELRRAAIAAGQPLPVFHDAIDWSEQEAEAAGTG 300 ASFDPVIFQLTLSLLAIHTTYDLLQQTMIDLGRHPEYIEPLRQEVVQLLREEGWKKTTLF 360 KMKLLDSAIKESQRMKPGSIVIMRRYVTEDITLSSGLTLKKGTRLNVDNRRLDDPKIYDN 420 PEVYNPYRFYDMRSEAGKDHGAQLVSTGSNHMGFGHGQHSCPGRFFAANEIKVALCHILV 480 KYDWKLCPDTETKPDTRGMIAKSSPVTDILIKRRESVELDLEAI 524 SEQIDNO:143 atgaaatatacaacctgtcagatgaacatcttcccttccctatggtcaatgaaaacgtcc 60 ttcagatggcctagaacatccaaatggtcttcagtttcactatatgacatgatgttgagg 120 actgtagccctgctgtcaggtagagctttcgttggcttaccactatgtagagatgaggga 180 tggttgcaggcaagtataggttatacagtccaatgcgtttcaataagagatcagcttttt 240 acttggagccccgtattgagaccaattatcgggccattcttgccctcagttagaagtgtg 300 aggagacacttgagatttgctgcagaaattatggctcctcttatcagtcaggctttacaa 360 gatgaaaagcaacacagggctgatacacttttagcagatcagaccgaaggtcgtggcacg 420 tttatttcttggttactgagacacctgccagaagaattacgtactcctgagcaagtagga 480 ctggaccagatgcttgtatcttttgccgcaattcacactacaacaatggctctaaccaaa 540 gtcgtgtgggaattagttaagagaccagaatacatcgaacccttgagaactgaaatgcaa 600 gatgtcttcgggcccgatgcggtttcaccagacatttgcattaataaagaggccctatcc 660 aggttgcataaattggattcttttattagggaggttcaaagatggtgtccttccactttt 720 gttactcctagccgtagagtgatgaagtccatgacgctgagcaacggaattaaactgcaa 780 cgtggtacgagtattgcttttcctgctcatgctatacatatgtcagaagaaacacctact 840 ttttcacctgacttttcttctgacttcgaaaatccttcccctagaatttttgatgggttc 900 cgttatttaaacttgaggtcaatcaagggacaaggaagccagcatcaagcggctactacc 960 ggtcctgattacttaatttttaaccatggtaaacatgcttgccctggtagattttttgct 1020 atttcagaaataaaaatgatcttgatagagttactagctaagtacgatttcaggttggaa 1080 gacggaaaaccagggcctgaactaatgagagttggtactgagacaagattggatacaaag 1140 gcaggtttggagatgagacgtagataa 1167 SEQIDNO:144 MKYTTCQMNIFPSLWSMKTSFRWPRTSKWSSVSLYDMMLRTVALLSGRAFVGLPLCRDEG 60 WLQASIGYTVQCVSIRDQLFTWSPVLRPIIGPFLPSVRSVRRHLRFAAEIMAPLISQALQ 120 DEKQHRADTLLADQTEGRGTFISWLLRHLPEELRTPEQVGLDQMLVSFAAIHTTIMALTK 180 VVWELVKRPEYIEPLRTEMQDVFGPDAVSPDICINKEALSRLHKLDSFIREVQRWCPSTF 240 VTPSRRVMKSMTLSNGIKLQRGTSIAFPAHAIHMSEETPTFSPDFSSDFENPSPRIFDGF 300 RYLNLRSIKGQGSQHQAATTGPDYLIFNHGKHACPGRFFAISEIKMILIELLAKYDFRLE 360 DGKPGPELMRVGTETRLDTKAGLEMRRR 388 SEQIDNO:145 atggctaaccattccagttcatactaccatgaattttacaaagatcattctcacacagtc 60 ttgacgctaatgtctgaaaaacctgtgattttgccatccttaatacttggaacctgtgcc 120 gtgttgttatgtatacaatggctgaaaccgcagcctttaatcatggtcaacggtagaaag 180 tttggagaattgtctaatgtaagagccaagcgtgattttaccttcggtgcgagacaattg 240 ttagaaaagggtctgaaaatgtcacctgacaaacccttcagaataatgggtgatgttggt 300 gagttgcatatcttgccaccaaaatatgcttatgaagtacgtaacaatgaaaaactatct 360 ttcaccatggcagccttcaaatggttttacgcacacttgcctggtttcgaaggtttcaga 420 gaaggtaccaatgaatcacatattatgaagttggtcgcaaggcatcaactaacacatcaa 480 ctgacactagttacaggtgcagtctccgaagagtgtgctcttgttttaaaggatgtttac 540 accgatagtcccgagtggcatgacatcaccgccaaggacgcaaatatgaaactgatggct 600 aggataactagtagagttttccttggtaaagaaatgtgcagaaaccctcaatggttacgt 660 atcacatctacatatgccgtgattgcattcagagcagtagaggaactaagattatggcca 720 tcatggttgagaccagttgttcaatggtttatgccacactgtacgcagtctagagccctt 780 gtgcaagaagcaagggacttaattaatccgttgttggaaaggagaagggaagaaaaagcg 840 gaggctgaaaggacgggtgagaaggtaacttacaatgacgctgtggaatggttggacgat 900 ttggccagggaaaagggagtgggttatgatcctgcctgcgctcaattaagcctaagtgtt 960 gccgccttacattcaactactgacttcttcactcaagttatgtttgatattgctcaaaat 1020 cctgagttgatagaaccgttaagagaagagatcatagcagtcttgggcaaacagggatgg 1080 tccaagaacagtttgtataatcttaaactgatggattctgtgttgaaagagtcacaacgt 1140 ctaaagccaatagccatcgctagcatgaggagatttactacacacaacgttaaattgtcc 1200 gatggcgtcatattacccaagaacaagttaacgttagttagcgcacatcagcactgggat 1260 ccagagtactacaaagacccattaaaatttgatggctatagattctttaacatgagacgt 1320 gagcccggcaaagaatcaaaagcacaactagtctctgcgaccccagaccatatggggttc 1380 ggttatggcctacatgcctgtcctggcaggttttttgcttctgaagaaatcaaaatcgca 1440 ctgtcacacatcttactgaagtatgattttaagcccgttgaaggtagttccatggagcca 1500 agaaagtatggtttgaacatgaacgcaaaccctactgcgaaactgagcgttcgtagaaga 1560 aaggaagagattgctatttaa 1581 SEQIDNO:146 MANHSSSYYHEFYKDHSHTVLTLMSEKPVILPSLILGTCAVLLCIQWLKPQPLIMVNGRK 60 FGELSNVRAKRDFTFGARQLLEKGLKMSPDKPFRIMGDVGELHILPPKYAYEVRNNEKLS 120 FTMAAFKWFYAHLPGFEGFREGTNESHIMKLVARHQLTHQLTLVTGAVSEECALVLKDVY 180 TDSPEWHDITAKDANMKLMARITSRVFLGKEMCRNPQWLRITSTYAVIAFRAVEELRLWP 240 SWLRPVVQWFMPHCTQSRALVQEARDLINPLLERRREEKAEAERTGEKVTYNDAVEWLDD 300 LAREKGVGYDPACAQLSLSVAALHSTTDFFTQVMFDIAQNPELIEPLREEIIAVLGKQGW 360 SKNSLYNLKLMDSVLKESQRLKPIAIASMRRFTTHNVKLSDGVILPKNKLTLVSAHQHWD 420 PEYYKDPLKFDGYRFFNMRREPGKESKAQLVSATPDHMGFGYGLHACPGRFFASEEIKIA 480 LSHILLKYDFKPVEGSSMEPRKYGLNMNANPTAKLSVRRRKEEIAI 526 SEQIDNO:147 atgtctaaggttgtgtacgtttctcatgatggtacccgtagggaactagatgttgctgat 60 ggcgtttcattaatgcaagctgcagtttcaaatggtatatatgatattgtcggcgattgt 120 ggtggaagtgcttcctgtgcgacgtgtcatgtctatgtaaacgaagcttttacggataag 180 gtcccagctgctaatgaaagagagataggtatgttggaatgtgttacagcggagttaaaa 240 ccaaattccagactatgctgccaaattattatgacccctgaactggatggaatagtagtt 300 gatgttcctgacagacaatggtaa 324 SEQIDNO:148 MSKVVYVSHDGTRRELDVADGVSLMQAAVSNGIYDIVGDCGGSASCATCHVYVNEAFTDK 60 VPAANEREIGMLECVTAELKPNSRLCCQIIMTPELDGIVVDVPDRQW 107 SEQIDNO:149 atgaacgcgaacgataatgtcgtaattgtgggtactggattagccggcgtagaggtggct 60 tttggattaagagcgtctggatgggaaggtaatatcaggctggttggggatgccactgtt 120 ataccacatcacttgcctcctctgtctaaagcttatttggccggcaaagctactgctgag 180 tccttatacttaaggactccggatgcctatgcagcccaaaatatccaattgttgggtgga 240 acgcaggtgacggccatcaacagagatcgtcaacaagttattttgagtgatggaagagca 300 ttggactacgatagactggttttggctacaggtggtagacctaggcctctaccagttgca 360 agtggtgccgttggaaaagccaacaatttcagatatttaaggactctagaagacgctgaa 420 tgcattaggaggcagttgatagcagacaatagactagttgtgattgggggcgggtacatc 480 ggcttagaagtagcagcgacagcaataaaagcgaacatgcacgttacactattagatacg 540 gccgcaagagtactagagagggtaaccgcacctccagtgtctgcattttatgaacatcta 600 catagagaggcgggtgttgacatcaggactggaactcaggtgtgcggtttcgaaatgtcc 660 acagatcaacaaaaggtcaccgcggttttgtgtgaagatgggacaagattgccagcagat 720 ttggtcattgccgggatcggtctaatccctaattgtgaactggcctctgccgcaggcctg 780 caagttgataatggtatcgttattaacgaacatatgcaaactagcgacccgttaataatg 840 gcggtcggagattgtgctcgttttcatagccagctatacgaccgttgggttagaatagag 900 tcagttcctaacgcattggaacaagccaggaaaatcgctgccatactttgtggtaaagta 960 ccaagagatgaggcagctccatggttctggagcgatcaatacgaaatcggtttgaaaatg 1020 gttggattgagcgagggctacgacagaattatcgttagaggtagcttggcccaaccagat 1080 ttttcagttttttacttacaaggtgatagagttctagcagtcgatactgtcaacagaccg 1140 gtagagttcaaccaaagcaagcaaatcattactgatagactacctgtcgaaccaaacctt 1200 cttggagatgaatccgtgccattgaaagaaatcattgccgccgcgaaggccgaactttcc 1260 agtgcttga 1269 SEQIDNO:150 MNANDNVVIVGTGLAGVEVAFGLRASGWEGNIRLVGDATVIPHHLPPLSKAYLAGKATAE 60 SLYLRTPDAYAAQNIQLLGGTQVTAINRDRQQVILSDGRALDYDRLVLATGGRPRPLPVA 120 SGAVGKANNFRYLRTLEDAECIRRQLIADNRLVVIGGGYIGLEVAATAIKANMHVILLDT 180 AARVLERVTAPPVSAFYEHLHREAGVDIRTGTQVCGFEMSTDQQKVTAVLCEDGTRLPAD 240 LVIAGIGLIPNCELASAAGLQVDNGIVINEHMQTSDPLIMAVGDCARFHSQLYDRWVRIE 300 SVPNALEQARKIAAILCGKVPRDEAAPWFWSDQYEIGLKMVGLSEGYDRIIVRGSLAQPD 360 FSVFYLQGDRVLAVDTVNRPVEFNQSKQIITDRLPVEPNLLGDESVPLKEIIAAAKAELS 420 SA 422 SEQIDNO:151 atggctaacactggtattccaaccgttgatgtttctttgttcttgtccgaaggtgaaaac 60 gaagctaagaagcaagctattcaaaccattaccgaagcctgttcttcttacggttttttc 120 caaatcgttaaccacggtatcccaatcgaatttttgaaagaagccttgcagttgtccaag 180 acattttttcattatccagacgaaatcaagttgcaatactctccaaaaccaggtgctcca 240 ttattggctggttttaacaagcaaaagaccaactgcgttgacaagaacgaatacgttttg 300 gtttttccaccaggctctaagtttaacatctatccacaagaaccaccacaattcaaagaa 360 accttggaagagatgttcttgaagttgtctgatgtctccttggtcatcgaatccattttg 420 aatgtttgtttgggtttgccaccaggtttcttgaagcaattcaacaatgatagatcctgg 480 gacttcatgaccaacttgtattattacccagctgctgatgttggtgaaaacggtttgatt 540 catcatgaagatgctaactgcatcaccttggttattcaagatgatgctggtggtttacaa 600 gtccaaaaagattctgaatggattccagttactccagttgaaggtgctatcgttgttaac 660 gttggtgatatcatccaagtcttgtccaacaagaagttcaagtctgctactcacagagtt 720 gttagacagaagggtaaagaaagatactccttcgctttcttcagatcattgcatggtgat 780 aagtgggttgaaccattgccagaattcaccaaagaaattggtgaaaagccaaagtacaag 840 ggcttcgaattcaatgaatacttggccttgagattgaagaacaagactcatccaccatct 900 agagttgaagatgagatttccatcaagcactacgagatcaactga 945 SEQIDNO:152 MANTGIPTVDVSLFLSEGENEAKKQAIQTITEACSSYGFFQIVNHGIPIEFLKEALQLSK 60 TFFHYPDEIKLQYSPKPGAPLLAGFNKQKTNCVDKNEYVLVFPPGSKFNIYPQEPPQFKE 120 TLEEMFLKLSDVSLVIESILNVCLGLPPGFLKQFNNDRSWDFMTNLYYYPAADVGENGLI 180 HHEDANCITLVIQDDAGGLQVQKDSEWIPVTPVEGAIVVNVGDIIQVLSNKKEKSATHRV 240 VRQKGKERYSFAFFRSLHGDKWVEPLPEFTKEIGEKPKYKGFEFNEYLALRLKNKTHPPS 300 RVEDEISIKHYEIN 314 SEQIDNO:153 atgtcctctagatctaccccaagaaaagaacctatttgcgcttctggtattttcccatcc 60 gttgataatcaagctttggaagttccaccaggtattcaaaagttgacctaccaatctttg 120 acctcctctacctctttcagattattgcaagttttgtccgatggtggtagagatattttg 180 agatgcaagatgttcgatgctgatttggctgctagagaaccaccaagatatattgctttg 240 tcttacacctggcacgaagaatctttgccaaaaacttttagaccagtcttgatcaacgac 300 aagtacttgaacgtttctttgaacttgtggaacttcttgcaaaactacagagaaacctcc 360 ggtgaaagaattatctggattgatcaaatctgcatcaatcaagaagataaggacgaatgc 420 gttcaacaaattggtcaaatgtgcaagatctaccaatgcgcttctatggatttgttctgg 480 attggtgaaccaggtgaaaatgctgaagctgttttggatttgttgtcctccttgaacaga 540 ttggaaacctacttgttggaatccggttcttctagaccaggtatttctgctttgttgaac 600 ccaattttcatgagagctgttggtttgccagaacatgataatccaatttggggttccttg 660 atgcaattcatttctagaactgctttccaaagagcctggatcattcaagaagttgctgtt 720 tctagaaccaccgctattttttgtggtttgttgatgttgccattcgatgttgttggtaga 780 gctgctacttttttggttgaatcctcttggattaaggttttccacgaaatgtacaacgtt 840 tctggtgctgctggttttattactggtatgatgaactgcagagtcagacatcaagaaggt 900 gaacatcaatctttggacttgttgttggcttctaccagaagattcaaagctacaaagcca 960 gttgataagatcttcgccttgattaacttggctgaatccggtagaaaagaagctttgcca 1020 ccagctttaagaccagattacagaaaatctatcgtcggtgttttcagagatgtcaccttg 1080 tacttgattagacaaggttccttggatgttttgtccggtgttgaagatgttaagttcaga 1140 caaatccacgaattgccatcttggattccagattactctgttcatcaagttgcctccatt 1200 ttgtgtatgccaccaagaccaggttggttgacattatatgctgctgctgttggtagagat 1260 gtttccgttcaaaattctccagctgatccaaacattttgaccttgtctgcttacaaggtt 1320 gacaccatttctaagattggttccattgccgaagaatccatctacttgactttggaaaaa 1380 tgggcctctatggttgatttttctgctgcttatccaactgttaacggtaacacttgtcca 1440 atgattgatgctttttggagaaccttgattggtaacattggtttgggtacttctcaatac 1500 ccagtttctgaagattgggctcattcttttgctgttttcgctttacaagccagagaagaa 1560 ttgcaacatcacttctcttcatcctctgatactgaaagagctgctttggaatctccaata 1620 gttactccaggtatcgactccattttgagattggttaaggatcattaccacggtaacaac 1680 gattctgatcaagatggtggtttgtacgaatctaccatgcatcatgtttcttggtacaga 1740 agattattcttgaccaacggtggttactttggtttggctcatccatcttctcaaccaggt 1800 gatgaagttgttttgttgtctggtggtagagttccattcgttgttagaagagtttctgcc 1860 gaaagaagagaatgctattctatcgttggtgaaacctacgttcatggtattatggacggt 1920 gaattattggatgctactgacggtaaatgggaagacttgcaattcaagtga 1971 SEQIDNO:154 MSSRSTPRKEPICASGIFPSVDNQALEVPPGIQKLTYQSLTSSTSFRLLQVLSDGGRDIL 60 RCKMFDADLAAREPPRYIALSYTWHEESLPKTFRPVLINDKYLNVSLNLWNFLQNYRETS 120 GERIIWIDQICINQEDKDECVQQIGQMCKIYQCASMDLFWIGEPGENAEAVLDLLSSLNR 180 LETYLLESGSSRPGISALLNPIFMRAVGLPEHDNPIWGSLMQFISRTAFQRAWIIQEVAV 240 SRTTAIFCGLLMLPFDVVGRAATFLVESSWIKVFHEMYNVSGAAGFITGMMNCRVRHQEG 300 EHQSLDLLLASTRRFKATKPVDKIFALINLAESGRKEALPPALRPDYRKSIVGVERDVIL 360 YLIRQGSLDVLSGVEDVKFRQIHELPSWIPDYSVHQVASILCMPPRPGWLTLYAAAVGRD 420 VSVQNSPADPNILTLSAYKVDTISKIGSIAEESIYLTLEKWASMVDFSAAYPTVNGNTCP 480 MIDAFWRTLIGNIGLGTSQYPVSEDWAHSFAVFALQAREELQHHFSSSSDTERAALESPI 540 VTPGIDSILRLVKDHYHGNNDSDQDGGLYESTMHHVSWYRRLFLTNGGYFGLAHPSSQPG 600 DEVVLLSGGRVPFVVRRVSAERRECYSIVGETYVHGIMDGELLDATDGKWEDLQFK 656 SEQIDNO:155 atggcagatagtttggccgttagacatgcagctgctttaaaattaatcgaagatttaacg 60 tcttcattgaatgatgtagaacctttaggagatattagcagagcgcaagcggattatgat 120 gctgccgaagaaagacatagaagggaacaagacccggctaggaaaagggcattgtgcagg 180 gaactagtaaggtacggcgatagactggaggaaattgagaagcaacataaggaagctgaa 240 gccaagtgtaaagaacaactagatctatttgacacaagactagcgaaagagggttaccgt 300 aaactagccacaagggcgtcctctataactggtactaaccaaactacacaccaatcatcc 360 aatacttctggaaacttaattcagacacctgatccgaactacggacaactttcaggcttt 420 acaaacgacagagctactcatgaaaacaccgaatcaccaggaacgttgcctcaatcttcc 480 actattaggaacacaatagaaccgaggctaactcccagtagaacaaattcagctgctcca 540 tccagaggtatttccacggatatcgatcaacaagtcagaatagaacctacagtccaaaca 600 gacaggtctaatcaaaggcgtgacaacccctctagttctagaccagccaagagacagaga 660 caaggcgcatctagtgaaacagttacagaaaggacaataaccttcgatgaggtatatcag 720 gggggaaaggctaggtggaaatacaggatcaccaaggtgcatggattatattacgtattc 780 ggctgtgagaagcatgaaaaacattttggtaaagaaaatccattacaatcagcaatgtcc 840 catttaaagggtaaaggccattcttgtaagagacctaatgctactcaagctttacgtagt 900 ctgggaatacaagttttaccatgtacggatagagatcttgagctaaacaacaaagccgtt 960 gacaggtacctggcagaacaagaagaaaagaataaaagaagaaaggcgtctgtaaaagat 1020 ttaagtcaagcacctcaaactggtgaaatttatatggcatggttcggagatgatgataaa 1080 ggctactggctacacgcctttctggtcataccattctttcctaggccaggcgacggcatg 1140 gacgttcaaactgtaacaggctccaatttaaacgatgatattccagcctgctataggttc 1200 gatgaaactactgatgggtataactggactgaggactacaaagaatatggcaaatacgca 1260 aataatagagtttacccaattatgtgtcttgtgggtcagatccctcataaagtcgattgg 1320 ttacctgtctgccatttcagaaaacttaatcttgaagatgaagacctagaggacaaagat 1380 gtcattaaagcgtttatgcgtaaaaataccaccgggaatacaggttacggcaacgaggtt 1440 gatgatgaatcagaagatctatatggtgattcctttgcaggtgatgatgatgtgcctaca 1500 agctctgaaaggagacagtctccgataggaaatagttctgaaaatatcaatactgatcaa 1560 agcatacaagcaggcgccaccgctgaaaatcaagaaagcggtaccttaggtccaaactta 1620 gcgactcaagaggttaaagatgaattagcgacgatcgggagaggcgatggtgctactagt 1680 gctgctgatcaaccggcaagagctaggcaaatgtctgtccgtcgtcgttggccttctgct 1740 agaaagggaccaccggatatggaaaccgttagcgattcagagtaa 1785 SEQIDNO:156 MADSLAVRHAAALKLIEDLTSSLNDVEPLGDISRAQADYDAAEERHRREQDPARKRALCR 60 ELVRYGDRLEEIEKQHKEAEAKCKEQLDLFDTRLAKEGYRKLATRASSITGTNQTTHQSS 120 NTSGNLIQTPDPNYGQLSGFTNDRATHENTESPGTLPQSSTIRNTIEPRLTPSRTNSAAP 180 SRGISTDIDQQVRIEPTVQTDRSNQRRDNPSSSRPAKRQRQGASSETVTERTITFDEVYQ 240 GGKARWKYRITKVHGLYYVFGCEKHEKHFGKENPLQSAMSHLKGKGHSCKRPNATQALRS 300 LGIQVLPCTDRDLELNNKAVDRYLAEQEEKNKRRKASVKDLSQAPQTGEIYMAWFGDDDK 360 GYWLHAFLVIPFFPRPGDGMDVQTVTGSNLNDDIPACYRFDETTDGYNWTEDYKEYGKYA 420 NNRVYPIMCLVGQIPHKVDWLPVCHFRKLNLEDEDLEDKDVIKAFMRKNTTGNTGYGNEV 480 DDESEDLYGDSFAGDDDVPTSSERRQSPIGNSSENINTDQSIQAGATAENQESGTLGPNL 540 ATQEVKDELATIGRGDGATSAADQPARARQMSVRRRWPSARKGPPDMETVSDSE 594 SEQIDNO:157 atggctcaattggataccttggatttggttgttttggccgttttgttggttggttctgtt 60 gcttattttaccaagggtacttattgggctgttgctaaagatccatatgcttctactggt 120 ccagctatgaatggtgctgctaaagctggtaaaaccagaaacattatcgaaaagatggaa 180 gaaaccggtaagaactgcgttattttctacggttctcaaactggtactgctgaagattat 240 gcttccagattggctaaagaaggttctcaaagattcggtttgaaaaccatggttgccgat 300 ttggaagaatacgactacgaaaacttggaccaattcccagaagataaggttgcttttttc 360 gttttggctacttacggtgaaggtgaacctactgataatgctgttgaattctaccaattc 420 ttcaccggtgatgatgttgcttttgaatctgcttctgctgacgaaaaaccattgtctaag 480 ttgaagtacgttgctttcggtttgggtaacaacacttacgaacattacaacgccatggtt 540 agacaagttgatgctgcttttcaaaagttgggtccacaaagaattggttctgctggtgaa 600 ggtgatgatggtgctggtactatggaagaagattttttggcttggaaagaacctatgtgg 660 gctgctttgtctgaatctatggacttggaagaaagagaagctgtttacgaaccagttttc 720 tgtgttaccgaaaacgaatctttgtccccagaagatgaaactgtttatttgggtgaacct 780 acccaatctcacttgcaaggtactccaaaaggtccatattctgctcataatccattcatt 840 gctccaatcgctgaatccagagaattattcactgttaaggacagaaactgcttgcacatg 900 gaaatttctattgccggttctaacttgtcttaccaaaccggtgatcatattgctgtttgg 960 ccaactaatgctggtgctgaagttgatagattcttgcaagtttttggtttggaaggtaag 1020 agagactccgttattaacatcaagggtattgatgttaccgccaaggttccaattccaact 1080 ccaactacttatgatgctgccgtcagatattacatggaagtttgtgctccagtctccaga 1140 caatttgttgctactttggctgcttttgctccagatgaagaatctaaagctgaaatcgtt 1200 agattgggttcccacaaggattactttcacgaaaaggttaccaatcaatgcttcaatatg 1260 gctcaagccttgcaatctattacctctaaaccattttctgccgtcccattctctttgttg 1320 attgaaggtattaccaagttgcaacctagatattactccatctcctcctcttcattggtt 1380 caaaaggataagatttccatcaccgccgttgttgaatctgttagattgccaggtgcttct 1440 catatggttaagggtgttactaccaattacttgttggccttgaagcaaaagcaaaacggt 1500 gatccatctccagatccacatggtttgacttattctattactggtccaagaaacaagtac 1560 gatggtatccatgttccagttcatgttagacactctaacttcaagttgccatctgatcca 1620 tctagaccaattatcatggttggtccaggtactggtgttgctccttttagaggttttatt 1680 caagaaagagctgctttggctgctaagggtgaaaaagttggtccaactgttttgttcttc 1740 ggttgcagaaaatccgacgaagatttcttgtacaaggacgaatggaaaacctaccaagat 1800 caattgggtgacaacttgaagattattaccgccttttctagagaaggtccacaaaaggtt 1860 tacgtccaacatagattgagagaacactccgaattggtttccgatttgttgaaacaaaag 1920 gccaccttttacgtttgtggtgatgctgctaatatggccagagaagttaatttggttttg 1980 ggtcaaattatcgctgcccaaagaggtttgccagctgaaaaaggtgaagaaatggtcaaa 2040 cacatgagaagaagaggtagataccaagaagatgtctggtcttaa 2085 SEQIDNO:158 MAQLDTLDLVVLAVLLVGSVAYFTKGTYWAVAKDPYASTGPAMNGAAKAGKTRNIIEKME 60 ETGKNCVIFYGSQTGTAEDYASRLAKEGSQRFGLKTMVADLEEYDYENLDQFPEDKVAFF 120 VLATYGEGEPTDNAVEFYQFFTGDDVAFESASADEKPLSKLKYVAFGLGNNTYEHYNAMV 180 RQVDAAFQKLGPQRIGSAGEGDDGAGTMEEDFLAWKEPMWAALSESMDLEEREAVYEPVF 240 CVTENESLSPEDETVYLGEPTQSHLQGTPKGPYSAHNPFIAPIAESRELFTVKDRNCLHM 300 EISIAGSNLSYQTGDHIAVWPTNAGAEVDRFLQVFGLEGKRDSVINIKGIDVTAKVPIPT 360 PTTYDAAVRYYMEVCAPVSRQFVATLAAFAPDEESKAEIVRLGSHKDYFHEKVTNQCFNM 420 AQALQSITSKPFSAVPFSLLIEGITKLQPRYYSISSSSLVQKDKISITAVVESVRLPGAS 480 HMVKGVTTNYLLALKQKQNGDPSPDPHGLTYSITGPRNKYDGIHVPVHVRHSNFKLPSDP 540 SRPIIMVGPGTGVAPFRGFIQERAALAAKGEKVGPTVLFFGCRKSDEDFLYKDEWKTYQD 600 QLGDNLKIITAFSREGPQKVYVQHRLREHSELVSDLLKQKATFYVCGDAANMAREVNLVL 660 GQIIAAQRGLPAEKGEEMVKHMRRRGRYQEDVWS 694 SEQIDNO:159 atgtccgccaagaaagaattcaccatgcaagatgttgctgaacacaatacctcttccgat 60 atctacatggttgttcacgataaggtttacgattgcaccaagttcttggatgaacatcca 120 ggtggtgaagaagttatgttggacgttgctggtcaagatgctactgaagcttttgaagat 180 gttggtcattctgatgaagccagagaagttttggatggtttgttggttggtgaattgaaa 240 agattgccaggtgatgaaggtccaaagagacaaattgctaactccaatcaaggttctggt 300 aaagctgatccagctggttcttctttgaatacttatgctatcgttgttgccgttggtttc 360 attgcttatgttgcttacaactacttgcaaaagcaacaagaagctcaaggtcaagcttct 420 gcttaa 426 SEQIDNO:160 MSAKKEFTMQDVAEHNTSSDIYMVVHDKVYDCTKFLDEHPGGEEVMLDVAGQDATEAFED 60 VGHSDEAREVLDGLLVGELKRLPGDEGPKRQIANSNQGSGKADPAGSSLNTYAIVVAVGF 120 IAYVAYNYLQKQQEAQGQASA 141 SEQIDNO:161 atggacttgaagaatcaaaccttcaccttccatttcgatatggctaaggatactggtatt 60 ccaaccgttgatttgtctgttttctctgctcaaaacgaaaccgaagctaagaagaaggct 120 ttcgaaactatctaccaagcctgttcttcttacggtttcttccaaatcgttaaccatggt 180 gttccaatcgaattcttggaagaagctttggaattgtccagaacattcttccattaccca 240 gatgacatcaagttgaagtactcttctaaaccaggtgctccattattggctggttttaac 300 aagcaaaagaagaactgcgttgacaagaacgaatacgttttggtttttccaccaggctct 360 aactacaatatctatccacaagaaccaccacaattcaaagaattattggaagaaatgttc 420 aagaagttgtccaaggtctgcttgttgttggaatctatcgttaacgaatctttgggtttg 480 ccaccagattttttgaagcagtacaacaacgatagatcctgggattttatgaccaccttg 540 tactacttttctgctactgaagaaggtgaaaacggtttgactcatcatgaagatggtaac 600 tgcattaccttggttttccaagatgataccggtggtttacaagttagaaaagatggtgaa 660 tggatcccagttgttccagttgaaggtgctatcgttgttaacattggtgatgttatccag 720 gtcttgtccaacaagaaattcaagtctgctacccacagagttgttagacaaaagggtaaa 780 gaaagattctcctacgccttcttccataacttgcatggtgataagtgggttgaaccattg 840 ccacaattcactgaagaaattggtgaaaagccaaagtacaagggtttccaattcaaggat 900 taccaagccttgagattgaagaacaaaactcatccaccatctagagttgaggacgaaatt 960 agaattacccactacgagatcagctaa 987 SEQIDNO:162 MDLKNQTFTFHFDMAKDTGIPTVDLSVFSAQNETEAKKKAFETIYQACSSYGFFQIVNHG 60 VPIEFLEEALELSRTFFHYPDDIKLKYSSKPGAPLLAGFNKQKKNCVDKNEYVLVFPPGS 120 NYNIYPQEPPQFKELLEEMFKKLSKVCLLLESIVNESLGLPPDFLKQYNNDRSWDFMTTL 180 YYFSATEEGENGLTHHEDGNCITLVFQDDTGGLQVRKDGEWIPVVPVEGAIVVNIGDVIQ 240 VLSNKKFKSATHRVVRQKGKERFSYAFFHNLHGDKWVEPLPQFTEEIGEKPKYKGFQFKD 300 YQALRLKNKTHPPSRVEDEIRITHYEIS 328 SEQIDNO:163 atggcctccatcacccatttcttacaagattttcaagctactccattcgctactgctttt 60 gctgttggtggtgtttctttgttgatattcttcttcttcatccgtggtttccactctact 120 aagaaaaacgaatattacaagttgccaccagttccagttgttccaggtttgccagttgtt 180 ggtaatttgttgcaattgaaagaaaagaagccatacaagactttcttgagatgggctgaa 240 attcatggtccaatctactctattagaactggtgcttctaccatggttgttgttaactct 300 actcatgttgccaaagaagctatggttaccagattctcttcaatctctaccagaaagttg 360 tccaaggctttggaattattgacctccaacaaatctatggttgccacctctgattacaac 420 gaatttcacaagatggtcaagaagtacatcttggccgaattattgggtgctaatgctcaa 480 aagagacacagaattcatagagacaccttgatcgaaaacgtcttgaacaaattgcatgcc 540 cataccaagaattctccattgcaagctgttaacttcagaaagatcttcgaatctgaatta 600 ttcggtttggctatgaagcaagccttgggttatgatgttgattccttgttcgttgaagaa 660 ttgggtactaccttgtccagagaagaaatctacaacgttttggtcagtgacatgttgaag 720 ggtgctattgaagttgattggagagactttttcccatacttgaaatggatcccaaacaag 780 tccttcgaaatgaagattcaaagattggcctctagaagacaagccgttatgaactctatt 840 gtcaaagaacaaaagaagtccattgcctctggtaagggtgaaaactgttacttgaattac 900 ttgttgtccgaagctaagactttgaccgaaaagcaaatttccattttggcctgggaaacc 960 attattgaaactgctgatacaactgttgttaccactgaatgggctatgtacgaattggct 1020 aaaaacccaaagcaacaagacagattatacaacgaaatccaaaacgtctgcggtactgat 1080 aagattaccgaagaacatttgtccaagttgccttacttgtctgctgtttttcacgaaacc 1140 ttgagaaagtattctccatctccattggttccattgagatacgctcatgaagatactcaa 1200 ttgggtggttattatgttccagccggtactgaaattgctgttaatatctacggttgcaac 1260 atggacaagaatcaatgggaaactccagaagaatggaagccagaaagatttttggacgaa 1320 aagtacgatccaatggacatgtacaagactatgtcttttggttccggtaaaagagtttgc 1380 gctggttctttacaagctagtttgattgcttgtacctccatcggtagattggttcaagaa 1440 tttgaatggagattgaaagacggtgaagttgaaaacgttgataccttgggtttgactacc 1500 cataagttgtatccaatgcaagctatcttgcaacctagaaactga 1545 SEQIDNO:164 MASITHFLQDFQATPFATAFAVGGVSLLIFFFFIRGFHSTKKNEYYKLPPVPVVPGLPVV 60 GNLLQLKEKKPYKTFLRWAEIHGPIYSIRTGASTMVVVNSTHVAKEAMVTRFSSISTRKL 120 SKALELLTSNKSMVATSDYNEFHKMVKKYILAELLGANAQKRHRIHRDTLIENVLNKLHA 180 HTKNSPLQAVNFRKIFESELFGLAMKQALGYDVDSLFVEELGTTLSREEIYNVLVSDMLK 240 GAIEVDWRDFFPYLKWIPNKSFEMKIQRLASRRQAVMNSIVKEQKKSIASGKGENCYLNY 300 LLSEAKTLTEKQISILAWETIIETADTTVVTTEWAMYELAKNPKQQDRLYNEIQNVCGTD 360 KITEEHLSKLPYLSAVFHETLRKYSPSPLVPLRYAHEDTQLGGYYVPAGTEIAVNIYGCN 420 MDKNQWETPEEWKPERFLDEKYDPMDMYKTMSEGSGKRVCAGSLQASLIACTSIGRLVQE 480 FEWRLKDGEVENVDTLGLTTHKLYPMQAILQPRN 514 SEQIDNO:165 atgcaatcagattcagtcaaagtctctccatttgatttggtttccgctgctatgaatggc 60 aaggcaatggaaaagttgaacgctagtgaatctgaagatccaacaacattgcctgcacta 120 aagatgctagttgaaaatagagaattgttgacactgttcacaacttccttcgcagttctt 180 attgggtgtcttgtatttctaatgtggagacgttcatcctctaaaaagctggtacaagat 240 ccagttccacaagttatcgttgtaaagaagaaagagaaggagtcagaggttgatgacggg 300 aaaaagaaagtttctattttctacggcacacaaacaggaactgccgaaggttttgctaaa 360 gcattagtcgaggaagcaaaagtgagatatgaaaagacctctttcaaggttatcgatcta 420 gatgactacgctgcagatgatgatgaatatgaggaaaaactgaaaaaggaatccttagcc 480 ttcttcttcttggccacatacggtgatggtgaacctactgataatgctgctaacttctac 540 aagtggttcacagaaggcgacgataaaggtgaatggctgaaaaagttacaatacggagta 600 tttggtttaggtaacagacaatatgaacatttcaacaagatcgctattgtagttgatgat 660 aaacttactgaaatgggagccaaaagattagtaccagtaggattaggggatgatgatcag 720 tgtatagaagatgacttcaccgcctggaaggaattggtatggccagaattggatcaactt 780 ttaagggacgaagatgatacttctgtgactaccccatacactgcagccgtattggagtac 840 agagtggtttaccatgataaaccagcagactcatatgctgaagatcaaacccatacaaac 900 ggtcatgttgttcatgatgcacagcatccttcaagatctaatgtggctttcaaaaaggaa 960 ctacacacctctcaatcagataggtcttgtactcacttagaattcgatatttctcacaca 1020 ggactgtcttacgaaactggcgatcacgttggcgtttattccgagaacttgtccgaagtt 1080 gtcgatgaagcactaaaactgttagggttatcaccagacacatacttctcagtccatgct 1140 gataaggaggatgggacacctatcggtggtgcttcactaccaccaccttttcctccttgc 1200 acattgagagacgctctaaccagatacgcagatgtcttatcctcacctaaaaaggtagct 1260 ttgctggcattggctgctcatgctagtgatcctagtgaagccgataggttaaagttcctg 1320 gcttcaccagccggaaaagatgaatatgcacaatggatcgtcgccaaccaacgttctttg 1380 ctagaagtgatgcaaagttttccatctgccaagcctccattaggtgtgttcttcgcagca 1440 gtagctccacgtttacaaccaagatactactctatcagttcatctcctaagatgtctcct 1500 aacagaatacatgttacatgtgctttggtgtacgagactactccagcaggcagaattcac 1560 agaggattgtgttcaacctggatgaaaaatgctgtccctttaacagagtcacctgattgc 1620 tctcaagcatccattttcgttagaacatcaaatttcagacttccagtggatccaaaagtt 1680 ccagtcattatgataggaccaggcactggtcttgccccattcaggggctttcttcaagag 1740 agattggccttgaaggaatctggtacagaattgggttcttctatctttttctttggttgc 1800 cgtaatagaaaagttgactttatctacgaggacgagcttaacaattttgttgagacagga 1860 gcattgtcagaattgatcgtcgcattttcaagagaagggactgccaaagagtacgttcag 1920 cacaagatgagtcaaaaagcctccgatatatggaaacttctaagtgaaggtgcctatctt 1980 tatgtctgtggcgatgcaaagggcatggccaaggatgtccatagaactctgcatacaatt 2040 gttcaggaacaagggagtctggattcttccaaggctgaattgtacgtcaaaaacttacag 2100 atgtctggaagatacttaagagatgtttggtaa 2133 SEQIDNO:166 MQSDSVKVSPFDLVSAAMNGKAMEKLNASESEDPTTLPALKMLVENRELLTLFTTSFAVL 60 IGCLVFLMWRRSSSKKLVQDPVPQVIVVKKKEKESEVDDGKKKVSIFYGTQTGTAEGFAK 120 ALVEEAKVRYEKTSFKVIDLDDYAADDDEYEEKLKKESLAFFFLATYGDGEPTDNAANFY 180 KWFTEGDDKGEWLKKLQYGVFGLGNRQYEHFNKIAIVVDDKLTEMGAKRLVPVGLGDDDQ 240 CIEDDFTAWKELVWPELDQLLRDEDDTSVTTPYTAAVLEYRVVYHDKPADSYAEDQTHTN 300 GHVVHDAQHPSRSNVAFKKELHTSQSDRSCTHLEFDISHTGLSYETGDHVGVYSENLSEV 360 VDEALKLLGLSPDTYFSVHADKEDGTPIGGASLPPPFPPCTLRDALTRYADVLSSPKKVA 420 LLALAAHASDPSEADRLKFLASPAGKDEYAQWIVANQRSLLEVMQSFPSAKPPLGVFFAA 480 VAPRLQPRYYSISSSPKMSPNRIHVTCALVYETTPAGRIHRGLCSTWMKNAVPLTESPDC 540 SQASIFVRTSNFRLPVDPKVPVIMIGPGTGLAPFRGFLQERLALKESGTELGSSIFFFGC 600 RNRKVDFIYEDELNNFVETGALSELIVAFSREGTAKEYVQHKMSQKASDIWKLLSEGAYL 660 YVCGDAKGMAKDVHRTLHTIVQEQGSLDSSKAELYVKNLQMSGRYLRDVW 710 SEQIDNO:167 atgtcctccaactccgatttggtcagaagattggaatctgttttgggtgtttctttcggt 60 ggttctgttactgattccgttgttgttattgctaccacctctattgctttggttatcggt 120 gttttggttttgttgtggagaagatcctctgacagatctagagaagttaagcaattggct 180 gttccaaagccagttactatcgttgaagaagaagatgaattcgaagttgcttctggtaag 240 accagagtttctattttctacggtactcaaactggtactgctgaaggttttgctaaggct 300 ttggctgaagaaatcaaagccagatacgaaaaagctgccgttaaggttattgatttggat 360 gattacacagccgaagatgacaaatacggtgaaaagttgaagaaagaaactatggccttc 420 ttcatgttggctacttatggtgatggtgaacctactgataatgctgctagattttacaag 480 tggttcaccgaaggtactgatagaggtgtttggttggaacatttgagatacggtgtattc 540 ggtttgggtaacagacaatacgaacacttcaacaagattgccaaggttgttgatgatttg 600 ttggttgaacaaggtgccaagagattggttactgttggtttgggtgatgatgatcaatgc 660 atcgaagatgatttctccgcttggaaagaagccttgtggccagaattggatcaattattg 720 caagatgataccaacaccgtttctactccatacactgctgttattccagaatacagagtt 780 gttatccacgatccatctgttacctcttatgaagatccatactctaacatggctaacggt 840 aatgcctcttacgatattcatcatccatgtagagctaacgttgccgtccaaaaagaattg 900 cataagccagaatctgacagaagttgcatccatttggaattcgatattttcgctactggt 960 ttgacttacgaaaccggtgatcatgttggtgtttacgctgataattgtgatgatactgta 1020 gaagaagccgctaagttgttgggtcaaccattggatttgttgttctccattcataccgat 1080 aacaacgacggtacttctttgggttcttctttgccaccaccatttccaggtccatgtact 1140 ttgagaactgctttggctagatatgccgatttgttgaatccaccaaaaaaggctgctttg 1200 attgctttagctgctcatgctgatgaaccatctgaagctgaaagattgaagttcttgtca 1260 tctccacaaggtaaggacgaatattctaaatgggttgtcggttcccaaagatccttggtt 1320 gaagttatggctgaatttccatctgctaaaccaccattgggtgtattttttgctgctgtt 1380 gttcctagattgcaacctagatattactccatctcttccagtccaagatttgctccacat 1440 agagttcatgttacttgcgctttggtttatggtccaactccaactggtagaattcacaga 1500 ggtgtatgttcattctggatgaagaatgttgtcccattggaaaagtctcaaaactgttct 1560 tgggccccaattttcatcagacaatctaatttcaagttgccagccgatcattctgttcca 1620 atagttatggttggtccaggtactggtttagctccttttagaggtttcttacaagaaaga 1680 ttggccttgaaagaagaaggtgctcaagttggtcctgctttgttgttttttggttgcaga 1740 aacagacaaatggacttcatctacgaagtcgaattgaacaactttgtcgaacaaggtgct 1800 ttgtccgaattgatcgttgctttttcaagagaaggtccatccaaagaatacgtccaacat 1860 aagatggttgaaaaggcagcttacatgtggaacttgatttctcaaggtggttacttctac 1920 gtttgtggtgatgctaaaggtatggctagagatgttcatagaacattgcataccatcgtc 1980 caacaagaagaaaaggttgattctaccaaggccgaatccatcgttaagaaattgcaaatg 2040 gacggtagatacttgagagatgtttggtga 2070 SEQIDNO:168 MSSNSDLVRRLESVLGVSFGGSVTDSVVVIATTSIALVIGVLVLLWRRSSDRSREVKQLA 60 VPKPVTIVEEEDEFEVASGKTRVSIFYGTQTGTAEGFAKALAEEIKARYEKAAVKVIDLD 120 DYTAEDDKYGEKLKKETMAFFMLATYGDGEPTDNAARFYKWFTEGTDRGVWLEHLRYGVF 180 GLGNRQYEHFNKIAKVVDDLLVEQGAKRLVTVGLGDDDQCIEDDFSAWKEALWPELDQLL 240 QDDTNTVSTPYTAVIPEYRVVIHDPSVTSYEDPYSNMANGNASYDIHHPCRANVAVQKEL 300 HKPESDRSCIHLEFDIFATGLTYETGDHVGVYADNCDDTVEEAAKLLGQPLDLLFSIHTD 360 NNDGTSLGSSLPPPFPGPCTLRTALARYADLLNPPKKAALIALAAHADEPSEAERLKFLS 420 SPQGKDEYSKWVVGSQRSLVEVMAEFPSAKPPLGVFFAAVVPRLQPRYYSISSSPRFAPH 480 RVHVTCALVYGPTPTGRIHRGVCSFWMKNVVPLEKSQNCSWAPIFIRQSNFKLPADHSVP 540 IVMVGPGTGLAPFRGFLQERLALKEEGAQVGPALLFFGCRNRQMDFIYEVELNNFVEQGA 600 LSELIVAFSREGPSKEYVQHKMVEKAAYMWNLISQGGYFYVCGDAKGMARDVHRTLHTIV 660 QQEEKVDSTKAESIVKKLQMDGRYLRDVW 689 SEQIDNO:169 atggctaccttgttggaacattttcaagctatgccattcgctattccaattgctttggct 60 gctttgtcttggttgtttttgttctacatcaaggtttctttcttctccaacaaatccgct 120 caagctaaattgccaccagttccagttgttccaggtttgccagttattggtaatttgttg 180 caattgaaagaaaagaagccataccaaaccttcactagatgggctgaagaatatggtcca 240 atctactctattagaactggtgcttctactatggttgtcttgaacactactcaagttgcc 300 aaagaagctatggttaccagatacttgtctatctctaccagaaagttgtccaacgccttg 360 aaaattttgaccgctgataagtgcatggttgccatttctgattacaacgatttccacaag 420 atgatcaagagatatatcttgtctaacgttttgggtccatctgcccaaaaaagacataga 480 tctaacagagataccttgagagccaacgtttgttctagattgcattcccaagttaagaac 540 tctccaagagaagctgtcaactttagaagagttttcgaatgggaattattcggtatcgct 600 ttgaaacaagccttcggtaaggatattgaaaagccaatctacgtcgaagaattgggtact 660 actttgtccagagatgaaatcttcaaggttttggtcttggacattatggaaggtgccatt 720 gaagttgattggagagattttttcccatacttgcgttggattccaaacaccagaatggaa 780 actaagatccaaagattatactttagaagaaaggccgttatgaccgccttgattaacgaa 840 caaaagaaaagaattgcctccggtgaagaaatcaactgctacatcgatttcttgttgaaa 900 gaaggtaagaccttgaccatggaccaaatctctatgttgttgtgggaaaccgttattgaa 960 actgctgataccacaatggttactactgaatgggctatgtacgaagttgctaaggattct 1020 aaaagacaagacagattataccaagaaatccaaaaggtctgcggttctgaaatggttaca 1080 gaagaatacttgtcccaattgccatacttgaatgctgttttccacgaaactttgagaaaa 1140 cattctccagctgctttggttccattgagatatgctcatgaagatactcaattgggtggt 1200 tattacattccagccggtactgaaattgccattaacatctacggttgcaacatggacaaa 1260 caccaatgggaatctccagaagaatggaagccagaaagatttttggatcctaagtttgac 1320 ccaatggacttgtacaaaactatggcttttggtgctggtaaaagagtttgcgctggttct 1380 ttacaagctatgttgattgcttgtccaaccatcggtagattggttcaagaatttgaatgg 1440 aagttgagagatggtgaagaagaaaacgttgatactgttggtttgaccacccataagaga 1500 tatccaatgcatgctattttgaagccaagatcttaa 1536 SEQIDNO:170 MATLLEHFQAMPFAIPIALAALSWLFLFYIKVSFFSNKSAQAKLPPVPVVPGLPVIGNLL 60 QLKEKKPYQTFTRWAEEYGPIYSIRTGASTMVVLNITQVAKEAMVTRYLSISTRKLSNAL 120 KILTADKCMVAISDYNDFHKMIKRYILSNVLGPSAQKRHRSNRDTLRANVCSRLHSQVKN 180 SPREAVNFRRVFEWELFGIALKQAFGKDIEKPIYVEELGTTLSRDEIFKVLVLDIMEGAI 240 EVDWRDFFPYLRWIPNTRMETKIQRLYFRRKAVMTALINEQKKRIASGEEINCYIDFLLK 300 EGKILTMDQISMLLWETVIETADTTMVITEWAMYEVAKDSKRQDRLYQEIQKVCGSEMVT 360 EEYLSQLPYLNAVFHETLRKHSPAALVPLRYAHEDTQLGGYYIPAGTEIAINIYGCNMDK 420 HQWESPEEWKPERFLDPKFDPMDLYKTMAFGAGKRVCAGSLQAMLIACPTIGRLVQEFEW 480 KLRDGEEENVDTVGLITHKRYPMHAILKPRS 511 SEQIDNO:171 atggatgctgtgacgggtttgttaactgtcccagcaaccgctataactattggtggaact 60 gctgtagcattggcggtagcgctaatcttttggtacctgaaatcctacacatcagctaga 120 agatcccaatcaaatcatcttccaagagtgcctgaagtcccaggtgttccattgttagga 180 aatctgttacaattgaaggagaaaaagccatacatgacttttacgagatgggcagcgaca 240 tatggacctatctatagtatcaaaactggggctacaagtatggttgtggtatcatctaat 300 gagatagccaaggaggcattggtgaccagattccaatccatatctacaaggaacttatct 360 aaagccctgaaagtacttacagcagataagacaatggtcgcaatgtcagattatgatgat 420 tatcataaaacagttaagagacacatactgaccgccgtcttgggtcctaatgcacagaaa 480 aagcatagaattcacagagatatcatgatggataacatatctactcaacttcatgaattc 540 gtgaaaaacaacccagaacaggaagaggtagaccttagaaaaatctttcaatctgagtta 600 ttcggcttagctatgagacaagccttaggaaaggatgttgaaagtttgtacgttgaagac 660 ctgaaaatcactatgaatagagacgaaatctttcaagtccttgttgttgatccaatgatg 720 ggagcaatcgatgttgattggagagacttctttccatacctaaagtgggtcccaaacaaa 780 aagttcgaaaatactattcaacaaatgtacatcagaagagaagctgttatgaaatcttta 840 atcaaagagcacaaaaagagaatagcgtcaggcgaaaagctaaatagttatatcgattac 900 cttttatctgaagctcaaactttaaccgatcagcaactattgatgtccttgtgggaacca 960 atcattgaatcttcagatacaacaatggtcacaacagaatgggcaatgtacgaattagct 1020 aaaaaccctaaattgcaagataggttgtacagagacattaagtccgtctgtggatctgaa 1080 aagataaccgaagagcatctatcacagctgccttacattacagctattttccacgaaaca 1140 ctgagaagacactcaccagttcctatcattcctctaagacatgtacatgaagataccgtt 1200 ctaggcggctaccatgttcctgctggcacagaacttgccgttaacatctacggttgcaac 1260 atggacaaaaacgtttgggaaaatccagaggaatggaacccagaaagattcatgaaagag 1320 aatgagacaattgattttcaaaagacgatggccttcggtggtggtaagagagtttgtgct 1380 ggttccttgcaagcccttttaactgcatctattgggattgggagaatggttcaagagttc 1440 gaatggaaactgaaggatatgactcaagaggaagtgaacacgataggcctaactacacaa 1500 atgttaagaccattgagagctattatcaaacctaggatctaa 1542 SEQIDNO:172 MDAVTGLLTVPATAITIGGTAVALAVALIFWYLKSYTSARRSQSNHLPRVPEVPGVPLLG 60 NLLQLKEKKPYMTFTRWAATYGPIYSIKTGATSMVVVSSNEIAKEALVTRFQSISTRNLS 120 KALKVLTADKTMVAMSDYDDYHKTVKRHILTAVLGPNAQKKHRIHRDIMMDNISTQLHEF 180 VKNNPEQEEVDLRKIFQSELFGLAMRQALGKDVESLYVEDLKITMNRDEIFQVLVVDPMM 240 GAIDVDWRDFFPYLKWVPNKKFENTIQQMYIRREAVMKSLIKEHKKRIASGEKLNSYIDY 300 LLSEAQTLTDQQLLMSLWEPIIESSDTTMVTTEWAMYELAKNPKLQDRLYRDIKSVCGSE 360 KITEEHLSQLPYITAIFHETLRRHSPVPIIPLRHVHEDTVLGGYHVPAGTELAVNIYGCN 420 MDKNVWENPEEWNPERFMKENETIDFQKTMAFGGGKRVCAGSLQALLTASIGIGRMVQEF 480 EWKLKDMTQEEVNTIGLITQMLRPLRAIIKPRI 513 SEQIDNO:173 atggccgaattggataccttggatatcgttgttttgggtgttatcttcttgggtactgtt 60 gcttacttcaccaaaggtaaattgtggggtgttactaaggatccatacgctaatggtttt 120 gctgctggtggtgcttctaaaccaggtagaactagaaatatcgttgaagccatggaagaa 180 tctggtaagaactgtgttgttttctacggttctcaaactggtactgctgaagattatgct 240 tccagattggctaaagaaggtaagagtagattcggtttgaacaccatgattgccgatttg 300 gaagattacgatttcgataacttggataccgtcccatctgataacatcgttatgtttgtt 360 ttggctacctacggtgaaggtgaacctactgataatgctgttgacttctacgaattcatt 420 accggtgaagatgcttctttcaacgaaggtaatgatccaccattgggtaacttgaattac 480 gttgcttttggtttgggtaacaacacctacgaacattacaactccatggttagaaacgtc 540 aacaaggctttggaaaaattgggtgctcatagaattggtgaagctggtgaaggtgatgat 600 ggtgctggtactatggaagaagattttttggcttggaaagacccaatgtgggaagccttg 660 gctaaaaagatgggtttggaagaaagagaagctgtctacgaacctattttcgccattaac 720 gaaagagatgatttgacccctgaagccaatgaagtttatttgggtgaacctaacaagttg 780 cacttggaaggtactgctaaaggtccattcaattctcacaacccatatattgctccaatc 840 gccgaatcttacgaattattctctgctaaggatagaaactgcttgcacatggaaattgac 900 atctctggttctaatttgaagtacgaaaccggtgatcatattgccatttggccaactaat 960 ccaggtgaagaagttaacaagttcttggacatcttggacttgtccggtaaacaacattct 1020 gttgttactgttaaggccttggaacctacagctaaagttccttttccaaatccaactacc 1080 tacgatgccattttgagataccatttggaaatttgcgctccagtctctagacaattcgtt 1140 tctactttggctgcttttgctccaaacgatgatattaaggctgaaatgaacagattgggt 1200 tccgataaggattacttccacgaaaaaactggtccacactactacaacattgctagattt 1260 ttggcctctgtctctaaaggtgaaaagtggactaagattccattctccgctttcattgaa 1320 ggtttgactaagttgcaacctagatattactccatctcctcctcatctttggttcaacct 1380 aagaagatctctattaccgccgttgttgaatcccaacaaattccaggtagagatgatcct 1440 tttagaggtgttgctaccaattacttgttcgccttgaaacaaaagcaaaacggtgatcca 1500 aatcctgctccatttggtcaatcttatgaattgactggtccaagaaacaagtacgatggt 1560 attcatgttccagttcacgttagacactctaactttaagttgccatctgatccaggtaag 1620 ccaattatcatgattggtccaggtactggtgttgctccattcagaggttttgttcaagaa 1680 agagctaagcaagctagagatggtgttgaagttggtaaaaccttgttgttcttcggttgt 1740 agaaagtccactgaagatttcatgtaccaaaaagaatggcaagaatacaaagaagcctta 1800 ggtgacaagttcgaaatgattactgccttctcaagagaaggttctaagaaggtttacgtc 1860 caacacagattgaaagaaagatccaaagaagtctccgatttgttgtctcaaaaggcctac 1920 ttttacgtttgtggtgatgctgctcatatggccagagaagttaatactgttttggcccaa 1980 attatcgctgaaggtagaggtgtatctgaagctaagggtgaagaaatcgttaagaacatg 2040 agatccgccaatcaataccaagtttgctctgattttgttaccttgcactgtaaagaaacc 2100 acctacgctaattccgaattgcaagaagatgtttggtcctaa 2142 SEQIDNO:174 MAELDTLDIVVLGVIFLGTVAYFTKGKLWGVTKDPYANGFAAGGASKPGRTRNIVEAMEE 60 SGKNCVVFYGSQTGTAEDYASRLAKEGKSRFGLNTMIADLEDYDFDNLDTVPSDNIVMFV 120 LATYGEGEPTDNAVDFYEFITGEDASFNEGNDPPLGNLNYVAFGLGNNTYEHYNSMVRNV 180 NKALEKLGAHRIGEAGEGDDGAGTMEEDFLAWKDPMWEALAKKMGLEEREAVYEPIFAIN 240 ERDDLTPEANEVYLGEPNKLHLEGTAKGPFNSHNPYIAPIAESYELFSAKDRNCLHMEID 300 ISGSNLKYETGDHIAIWPTNPGEEVNKFLDILDLSGKQHSVVTVKALEPTAKVPFPNPTT 360 YDAILRYHLEICAPVSRQFVSTLAAFAPNDDIKAEMNRLGSDKDYFHEKTGPHYYNIARF 420 LASVSKGEKWTKIPFSAFIEGLTKLQPRYYSISSSSLVQPKKISITAVVESQQIPGRDDP 480 FRGVATNYLFALKQKQNGDPNPAPFGQSYELTGPRNKYDGIHVPVHVRHSNFKLPSDPGK 540 PIIMIGPGTGVAPFRGFVQERAKQARDGVEVGKTLLFFGCRKSTEDFMYQKEWQEYKEAL 600 GDKFEMITAFSREGSKKVYVQHRLKERSKEVSDLLSQKAYFYVCGDAAHMAREVNTVLAQ 660 IIAEGRGVSEAKGEEIVKNMRSANQYQVCSDFVTLHCKETTYANSELQEDVWS 713 SEQIDNO:175 atggcttcagaaaaagaaattaggagagagagattcttgaacgttttccctaaattagta 60 gaggaattgaacgcatcgcttttggcttacggtatgcctaaggaagcatgtgactggtat 120 gcccactcattgaactacaacactccaggcggtaagctaaatagaggtttgtccgttgtg 180 gacacgtatgctattctctccaacaagaccgttgaacaattggggcaagaagaatacgaa 240 aaggttgccattctaggttggtgcattgagttgttgcaggcttacttcttggtcgccgat 300 gatatgatggacaagtccattaccagaagaggccaaccatgttggtacaaggttcctgaa 360 gttggggaaattgccatcaatgacgcattcatgttagaggctgctatctacaagcttttg 420 aaatctcacttcagaaacgaaaaatactacatagatatcaccgaattgttccatgaggtc 480 accttccaaaccgaattgggccaattgatggacttaatcactgcacctgaagacaaagtc 540 gacttgagtaagttctccctaaagaagcactccttcatagttactttcaagactgcttac 600 tattctttctacttgcctgtcgcattggccatgtacgttgccggtatcacggatgaaaag 660 gatttgaaacaagccagagatgtcttgattccattgggtgaatacttccaaattcaagat 720 gactacttagactgcttcggtaccccagaacagatcggtaagatcggtacagatatccaa 780 gataacaaatgttcttgggtaatcaacaaggcattggaacttgcttccgcagaacaaaga 840 aagactttagacgaaaattacggtaagaaggactcagtcgcagaagccaaatgcaaaaag 900 attttcaatgacttgaaaattgaacagctataccacgaatatgaagagtctattgccaag 960 gatttgaaggccaaaatttctcaggtcgatgagtctcgtggcttcaaagctgatgtctta 1020 actgcgttcttgaacaaagtttacaagagaagcaaatag 1059 SEQIDNO:176 MASEKEIRRERFLNVFPKLVEELNASLLAYGMPKEACDWYAHSLNYNTPGGKLNRGLSVV 60 DTYAILSNKTVEQLGQEEYEKVAILGWCIELLQAYFLVADDMMDKSITRRGQPCWYKVPE 120 VGEIAINDAFMLEAAIYKLLKSHFRNEKYYIDITELFHEVTFQTELGQLMDLITAPEDKV 180 DLSKFSLKKHSFIVTFKTAYYSFYLPVALAMYVAGITDEKDLKQARDVLIPLGEYFQIQD 240 DYLDCFGTPEQIGKIGTDIQDNKCSWVINKALELASAEQRKTLDENYGKKDSVAEAKCKK 300 IFNDLKIEQLYHEYEESIAKDLKAKISQVDESRGFKADVLTAFLNKVYKRSK 352 SEQIDNO:177 atggtcgcacaaactttcaacctggatacctacttatcccaaagacaacaacaagttgaa 60 gaggccctaagtgctgctcttgtgccagcttatcctgagagaatatacgaagctatgaga 120 tactccctcctggcaggtggcaaaagattaagacctatcttatgtttagctgcttgcgaa 180 ttggcaggtggttctgttgaacaagccatgccaactgcgtgtgcacttgaaatgatccat 240 acaatgtcactaattcatgatgacctgccagccatggataacgatgatttcagaagagga 300 aagccaactaatcacaaggtgttcggggaagatatagccatcttagcgggtgatgcgctt 360 ttagcttacgcttttgaacatattgcttctcaaacaagaggagtaccacctcaattggtg 420 ctacaagttattgctagaatcggacacgccgttgctgcaacaggcctcgttggaggccaa 480 gtcgtagaccttgaatctgaaggtaaagctatttccttagaaacattggagtatattcac 540 tcacataagactggagccttgctggaagcatcagttgtctcaggcggtattctcgcaggg 600 gcagatgaagagcttttggccagattgtctcattacgctagagatataggcttggctttt 660 caaatcgtcgatgatatcctggatgttactgctacatctgaacagttggggaaaaccgct 720 ggtaaagaccaggcagccgcaaaggcaacttatccaagtctattgggtttagaagcctct 780 agacagaaagcggaagagttgattcaatctgctaaggaagccttaagaccttacggttca 840 caagcagagccactcctagcgctggcagacttcatcacacgtcgtcagcattaa 894 SEQIDNO:178 MVAQTFNLDTYLSQRQQQVEEALSAALVPAYPERIYEAMRYSLLAGGKRLRPILCLAACE 60 LAGGSVEQAMPTACALEMIHTMSLIHDDLPAMDNDDFRRGKPTNHKVFGEDIAILAGDAL 120 LAYAFEHIASQTRGVPPQLVLQVIARIGHAVAATGLVGGQVVDLESEGKAISLETLEYIH 180 SHKTGALLEASVVSGGILAGADEELLARLSHYARDIGLAFQIVDDILDVTATSEQLGKTA 240 GKDQAAAKATYPSLLGLEASRQKAEELIQSAKEALRPYGSQAEPLLALADFITRRQH 297 SEQIDNO:179 atggcacagcacacatcagaatccgcagctgtcgcaaagggcagcagtttgacccctata 60 gtgagaactgacgctgagtcaaggagaacaagatggccaaccgatgacgatgacgccgaa 120 cctttagtggatgagatcagggcaatgcttacttccatgtctgatggtgacatttccgtg 180 agcgcatacgatacagcctgggtcggattggttccaagattagacggcggtgaaggtcct 240 caatttccagcagctgtgagatggataagaaataaccagttgcctgacggaagttggggc 300 gatgccgcattattctctgcctatgacaggcttatcaatacccttgcctgcgttgtaact 360 ttgacaaggtggtccctagaaccagagatgagaggtagaggactatcttttttgggtagg 420 aacatgtggaaattagcaactgaagatgaagagtcaatgcctattggcttcgaattagca 480 tttccatctttgatagagcttgctaagagcctaggtgtccatgacttcccttatgatcac 540 caggccctacaaggaatctactcttcaagagagatcaaaatgaagaggattccaaaagaa 600 gtgatgcataccgttccaacatcaatattgcacagtttggagggtatgcctggcctagat 660 tgggctaaactacttaaactacagagcagcgacggaagttttttgttctcaccagctgcc 720 actgcatatgctttaatgaataccggagatgacaggtgttttagctacatcgatagaaca 780 gtaaagaaattcaacggcggcgtccctaatgtttatccagtggatctatttgaacatatt 840 tgggccgttgatagacttgaaagattaggaatctccaggtacttccaaaaggagatcgaa 900 caatgcatggattatgtaaacaggcattggactgaggacggtatttgttgggcaaggaac 960 tctgatgtcaaagaggtggacgacacagctatggcctttagacttcttaggttgcacggc 1020 tacagcgtcagtcctgatgtgtttaaaaacttcgaaaaggacggtgaatttttcgcattt 1080 gtcggacagtctaatcaagctgttaccggtatgtacaacttaaacagagcaagccagata 1140 tccttcccaggcgaggatgtgcttcatagagctggtgccttctcatatgagttcttgagg 1200 agaaaagaagcagagggagctttgagggacaagtggatcatttctaaagatctacctggt 1260 gaagttgtgtatactttggattttccatggtacggcaacttacctagagtcgaggccaga 1320 gactacctagagcaatacggaggtggtgatgacgtttggattggcaagacattgtatagg 1380 atgccacttgtaaacaatgatgtatatttggaattggcaagaatggatttcaaccactgc 1440 caggctttgcatcagttagagtggcaaggactaaaaagatggtatactgaaaataggttg 1500 atggactttggtgtcgcccaagaagatgcccttagagcttattttcttgcagccgcatct 1560 gtttacgagccttgtagagctgccgagaggcttgcatgggctagagccgcaatactagct 1620 aacgccgtgagcacccacttaagaaatagcccatcattcagagaaaggttagagcattct 1680 cttaggtgtagacctagtgaagagacagatggctcctggtttaactcctcaagtggctct 1740 gatgcagttttagtaaaggctgtcttaagacttactgattcattagccagggaagcacag 1800 ccaatccatggaggtgacccagaagatattatacacaagttgttaagatctgcttgggcc 1860 gagtgggttagggaaaaggcagacgctgccgatagcgtgtgcaatggtagttctgcagta 1920 gaacaagagggatcaagaatggtccatgataaacagacctgtctattattggctagaatg 1980 atcgaaatttctgccggtagggcagctggtgaagcagccagtgaggacggcgatagaaga 2040 ataattcaattaacaggctccatctgcgacagtcttaagcaaaaaatgctagtttcacag 2100 gaccctgaaaaaaatgaagagatgatgtctcacgtggatgacgaattgaagttgaggatt 2160 agagagttcgttcaatatttgcttagactaggtgaaaaaaagactggatctagcgaaacc 2220 aggcaaacatttttaagtatagtgaaatcatgttactatgctgctcattgcccacctcat 2280 gtcgttgatagacacattagtagagtgattttcgagccagtaagtgccgcaaagtaa 2337 SEQIDNO:180 MAQHTSESAAVAKGSSLTPIVRTDAESRRTRWPTDDDDAEPLVDEIRAMLTSMSDGDISV 60 SAYDTAWVGLVPRLDGGEGPQFPAAVRWIRNNQLPDGSWGDAALFSAYDRLINTLACVVT 120 LTRWSLEPEMRGRGLSFLGRNMWKLATEDEESMPIGFELAFPSLIELAKSLGVHDFPYDH 180 QALQGIYSSREIKMKRIPKEVMHTVPTSILHSLEGMPGLDWAKLLKLQSSDGSFLFSPAA 240 TAYALMNTGDDRCFSYIDRTVKKFNGGVPNVYPVDLFEHIWAVDRLERLGISRYFQKEIE 300 QCMDYVNRHWTEDGICWARNSDVKEVDDTAMAFRLLRLHGYSVSPDVFKNFEKDGEFFAF 360 VGQSNQAVTGMYNLNRASQISFPGEDVLHRAGAFSYEFLRRKEAEGALRDKWIISKDLPG 420 EVVYTLDFPWYGNLPRVEARDYLEQYGGGDDVWIGKTLYRMPLVNNDVYLELARMDFNHC 480 QALHQLEWQGLKRWYTENRLMDFGVAQEDALRAYFLAAASVYEPCRAAERLAWARAAILA 540 NAVSTHLRNSPSFRERLEHSLRCRPSEETDGSWFNSSSGSDAVLVKAVLRLTDSLAREAQ 600 PIHGGDPEDIIHKLLRSAWAEWVREKADAADSVCNGSSAVEQEGSRMVHDKQTCLLLARM 660 IEISAGRAAGEAASEDGDRRIIQLTGSICDSLKQKMLVSQDPEKNEEMMSHVDDELKLRI 720 REFVQYLLRLGEKKTGSSETRQTFLSIVKSCYYAAHCPPHVVDRHISRVIFEPVSAAK 778 SEQIDNO:181 atgtctattaatttgagatcttccggttgtagctccccaataagcgcaactttggaaagg 60 ggtctagactctgaagttcaaacaagagcaaacaatgtatcttttgagcagaccaaagag 120 aagatcaggaaaatgcttgagaaggtcgagttgagcgtgagtgcctatgacactagttgg 180 gtagctatggtcccatcaccatccagtcaaaacgcacctcttttcccacagtgcgtcaaa 240 tggctacttgataatcaacatgaggacggctcttggggattggataaccacgaccatcag 300 agcttaaagaaagatgtgttgtcatccacattagcctctatcctagctcttaagaaatgg 360 ggaataggcgaaagacagatcaataagggtctacagttcattgaattaaactctgcacta 420 gttaccgatgaaactatacaaaaacctacaggtttcgacatcatttttccaggaatgatt 480 aagtacgccagggaccttaatttgaccatacctcttggctcagaagtagtcgacgatatg 540 atcaggaaaagagatctagacttaaagtgtgatagcgagaaattcagcaaaggtagagag 600 gcttatcttgcctatgttcttgaaggaactaggaacttgaaggactgggacttaattgtg 660 aaatatcagagaaagaacggtagtctatttgatagtccagctacaaccgccgcagctttc 720 actcaatttggcaatgacggttgcttgaggtacttatgttcacttttacagaaattcgag 780 gccgcagtgcctagtgtatatccatttgatcaatacgctagattaagcataatcgtcact 840 ttagaatcattgggaattgacagagatttcaagactgagataaaaagcatattggatgag 900 acctataggtactggcttagaggtgacgaagaaatttgcctagatttggccacatgtgca 960 cttgcttttaggttgcttttagcccacggctatgacgtgtcatacgatcctctaaagcca 1020 tttgcagaggaatctggtttcagcgatacccttgagggatatgttaaaaacaccttttcc 1080 gtattagagcttttcaaggctgcccaaagttaccctcatgagagtgctttgaaaaagcag 1140 tgttgctggacaaaacaatatctagaaatggaactaagttcatgggttaaaacaagcgtt 1200 agggacaagtacttgaaaaaggaagtggaggatgctttggcatttccatcatatgcctct 1260 ttagaaagaagtgaccacagaaggaaaattcttaatggctcagcagttgaaaacacaaga 1320 gtaaccaagacctcttacaggttgcataatatatgtacatcagatatcttaaaacttgct 1380 gtcgacgatttcaacttttgccaatctattcatagagaggaaatggaaagattggataga 1440 tggatagtggagaatagactacaggaattaaagttcgccagacaaaaattggcttactgt 1500 tactttagtggcgctgccacactattctctccagaattgtctgacgcaaggatctcatgg 1560 gctaagggaggtgttctaaccacagtagtcgatgacttttttgatgttggcggtagtaaa 1620 gaagagcttgagaacttaattcacttggtggaaaagtgggatcttaatggagttcctgaa 1680 tactcttcagagcatgtagaaataattttctctgtcctaagagacactatcttagaaacc 1740 ggtgataaagcctttacatatcagggcagaaacgttactcaccatattgtgaaaatatgg 1800 ttggacttacttaagagcatgctaagggaggctgaatggtccagtgacaaatcaacccca 1860 tctttggaagattacatggagaatgcctatatcagcttcgcattaggtcctattgtattg 1920 ccagctacataccttataggacctccactacctgaaaagactgtcgactcccaccaatat 1980 aatcaattatacaaattggttagtaccatgggtagactattaaacgatatccagggcttt 2040 aagagggaatcagccgagggaaaacttaatgcagtgtctctacatatgaagcatgaaaga 2100 gacaacagaagcaaagaggttattatagaatccatgaaaggattggctgaaaggaaaaga 2160 gaggaattacacaaacttgtactagaagagaaaggtagtgtcgttccaagagaatgcaag 2220 gaagccttcttaaaaatgtcaaaagtgttgaaccttttttataggaaggatgatggcttc 2280 acatctaacgacttgatgagccttgtgaaatccgtcatctacgagcctgtttcacttcaa 2340 aaggagagtctaacttga 2358 SEQIDNO:182 MSINLRSSGCSSPISATLERGLDSEVQTRANNVSFEQTKEKIRKMLEKVELSVSAYDTSW 60 VAMVPSPSSQNAPLFPQCVKWLLDNQHEDGSWGLDNHDHQSLKKDVLSSTLASILALKKW 120 GIGERQINKGLQFIELNSALVIDETIQKPTGFDIIFPGMIKYARDLNLTIPLGSEVVDDM 180 IRKRDLDLKCDSEKFSKGREAYLAYVLEGTRNLKDWDLIVKYQRKNGSLFDSPATTAAAF 240 TQFGNDGCLRYLCSLLQKFEAAVPSVYPFDQYARLSIIVTLESLGIDRDFKTEIKSILDE 300 TYRYWLRGDEEICLDLATCALAFRLLLAHGYDVSYDPLKPFAEESGFSDTLEGYVKNTFS 360 VLELFKAAQSYPHESALKKQCCWTKQYLEMELSSWVKTSVRDKYLKKEVEDALAFPSYAS 420 LERSDHRRKILNGSAVENTRVIKTSYRLHNICTSDILKLAVDDFNFCQSIHREEMERLDR 480 WIVENRLQELKFARQKLAYCYFSGAATLFSPELSDARISWAKGGVLTTVVDDFFDVGGSK 540 EELENLIHLVEKWDLNGVPEYSSEHVEIIFSVLRDTILETGDKAFTYQGRNVTHHIVKIW 600 LDLLKSMLREAEWSSDKSTPSLEDYMENAYISFALGPIVLPATYLIGPPLPEKTVDSHQY 660 NQLYKLVSTMGRLLNDIQGFKRESAEGKLNAVSLHMKHERDNRSKEVIIESMKGLAERKR 720 EELHKLVLEEKGSVVPRECKEAFLKMSKVLNLFYRKDDGFTSNDLMSLVKSVIYEPVSLQ 780 KESLT 785 SEQIDNO:183 atgatgagtaattttgttactttgattgagccattagaacttaccggttcaagggttcta 60 agaatcgccgtggcgttcgcggctttgtgtggtgccaccggtttgctggccttttcctgg 120 tggatttataagcaaagctctagtaagccaacgcttccgtaccctgtagttggcgataca 180 catgcacaaagcttggaaaaaaatttaatcaaaggaatgcaacaatacagagacagtcca 240 tttttcctagccggaagcagacctccgttactaattttgcctatgtccgtttttcatgag 300 atccataacatgcctaacgaatatatatctattatcgttgagcacgaagacaaattccaa 360 ggcaagtatacccatataactacaataagaccagaaattcctgcaacaataagacaagat 420 ttaacaaggaacatgccaaatatcatactagaattgcaagatgaactaacatacgcctca 480 gaccaatggcctagaacatccaaatggtcttcagtttcactatatgacatgatgttgagg 540 actgtagccctgctgtcaggtagagctttcgttggcttaccactatgtagagatgaggga 600 tggttgcaggcaagtataggttatacagtccaatgcgtttcaataagagatcagcttttt 660 acttggagccccgtattgagaccaattatcgggccattcttgccctcagttagaagtgtg 720 aggagacacttgagatttgctgcagaaattatggctcctcttatcagtcaggctttacaa 780 gatgaaaagcaacacagggctgatacacttttagcagatcagaccgaaggtcgtggcacg 840 tttatttcttggttactgagacacctgccagaagaattacgtactcctgagcaagtagga 900 ctggaccagatgcttgtatcttttgccgcaattcacactacaacaatggctctaaccaaa 960 gtcgtgtgggaattagttaagagaccagaatacatcgaacccttgagaactgaaatgcaa 1020 gatgtcttcgggcccgatgcggtttcaccagacatttgcattaataaagaggccctatcc 1080 aggttgcataaattggattcttttattagggaggttcaaagatggtgtccttccactttt 1140 gttactcctagccgtagagtgatgaagtccatgacgctgagcaacggaattaaactgcaa 1200 cgtggtacgagtattgcttttcctgctcatgctatacatatgtcagaagaaacacctact 1260 ttttcacctgacttttcttctgacttcgaaaatccttcccctagaatttttgatgggttc 1320 cgttatttaaacttgaggtcaatcaagggacaaggaagccagcatcaagcggctactacc 1380 ggtcctgattacttaatttttaaccatggtaaacatgcttgccctggtagattttttgct 1440 atttcagaaataaaaatgatcttgatagagttactagctaagtacgatttcaggttggaa 1500 gacggaaaaccagggcctgaactaatgagagttggtactgagacaagattggatacaaag 1560 gcaggtttggagatgagacgtagataa 1587 SEQIDNO:184 MMSNFVTLIEPLELTGSRVLRIAVAFAALCGATGLLAFSWWIYKQSSSKPTLPYPVVGDT 60 HAQSLEKNLIKGMQQYRDSPFFLAGSRPPLLILPMSVFHEIHNMPNEYISIIVEHEDKFQ 120 GKYTHITTIRPEIPATIRQDLTRNMPNIILELQDELTYASDQWPRTSKWSSVSLYDMMLR 180 TVALLSGRAFVGLPLCRDEGWLQASIGYTVQCVSIRDQLFTWSPVLRPIIGPFLPSVRSV 240 RRHLRFAAEIMAPLISQALQDEKQHRADTLLADQTEGRGTFISWLLRHLPEELRTPEQVG 300 LDQMLVSFAAIHTTIMALTKVVWELVKRPEYIEPLRTEMQDVFGPDAVSPDICINKEALS 360 RLHKLDSFIREVQRWCPSTFVITSRRVMKSMTLSNGIKLQRGTSIAFPAHAIHMSEETPT 420 FSPDFSSDFENPSPRIFDGFRYLNLRSIKGQGSQHQAATTGPDYLIFNHGKHACPGRFFA 480 ISEIKMILIELLAKYDFRLEDGKPGPELMRVGTETRLDTKAGLEMRRR 528 SEQIDNO:185 atgatgtccaacttcgttaccttgatcgaaccattggaattgactggttctagagttttg 60 agaattgctgttgcttttgctgctttgtgtggtgctactggtttgttggctttttcttgg 120 tggatctacaagcaatcttcttcaaaacctactttgccatacccagttgttggtgatact 180 catgctcaatctttggaaaagaacttgattaagggtatgcaacaatacagagactcccca 240 ttctttttggctggttcaagaccaccattattgatcttgccaatgtctgttttccacgaa 300 atccataacatgccaaacgaatatatctccatcatcgttgaacacgaagataagttccaa 360 ggtaaatacacccatatcactaccatcagaccagaaattccagctaccattagacaagat 420 ttgaccagaaacatgcctaacatcatcttggaattgcaagacgaattgacctacgcttct 480 gatcaatggccaagaacttctaagtggtcctctgtttcattatacgacatgatgttgaga 540 accgttgctttgttgtctggtagagcttttgttggtttgccattgtgtagagatgaaggt 600 tggttgcaagcttctattggttacactgttcaatgcgtgtctatcagagatcagttgttt 660 acttggtccccagttttgaggccaattattggtccatttttgccatccgttagatctgtt 720 agaaggcatttgagattcgctgctgaaattatggctccattgatttctcaagccttgcaa 780 gacgaaaaacaacatagagctgataccttgttggctgatcaaactgaaggtagaggtact 840 ttcatttcctggttgttgagacatttgccagaagaattgagaaccccagaacaagttggt 900 ttggatcaaatgttggtttcctttgctgctattcataccactactatggctttgacaaag 960 gttgtttgggaattggtaaaaaggccagagtacattgaaccattgagaaccgaaatgcaa 1020 gatgtttttggtccagatgctgtttctccagatatctgcattaacaaagaagccttgtcc 1080 agattgcacaagttggattctttcatcagagaagttcaaagatggtgtccatctactttc 1140 gttactccatctagaagagtcatgaagtctatgactttgtccaacggtatcaagttgcaa 1200 agaggtacttctattgcttttccagctcatgccattcacatgtctgaagaaactccaaca 1260 ttttccccagatttctcttccgattttgaaaacccatccccaagaattttcgacggtttt 1320 agatacttgaacttgaggtccattaagggtcaaggttcacaacatcaagctgctactact 1380 ggtccagattacttgattttcaatcatggtaaacatgcctgcccaggtagattttttgct 1440 atctctgaaatcaagatgattttgatcgagttgttggccaagtacgacttcagattggaa 1500 gatggtaaaccaggtccagaattgatgagagttggtactgaaactagattggataccaaa 1560 gctggtttggaaatgagaagaaggtga 1587 SEQIDNO:186 MMSNFVTLIEPLELTGSRVLRIAVAFAALCGATGLLAFSWWIYKQSSSKPTLPYPVVGDT 60 HAQSLEKNLIKGMQQYRDSPFFLAGSRPPLLILPMSVFHEIHNMPNEYISIIVEHEDKFQ 120 GKYTHITTIRPEIPATIRQDLTRNMPNIILELQDELTYASDQWPRTSKWSSVSLYDMMLR 180 TVALLSGRAFVGLPLCRDEGWLQASIGYTVQCVSIRDQLFTWSPVLRPIIGPFLPSVRSV 240 RRHLRFAAEIMAPLISQALQDEKQHRADTLLADQTEGRGTFISWLLRHLPEELRTPEQVG 300 LDQMLVSFAAIHTTIMALTKVVWELVKRPEYIEPLRTEMQDVFGPDAVSPDICINKEALS 360 RLHKLDSFIREVQRWCPSTFVTPSRRVMKSMTLSNGIKLQRGTSIAFPAHAIHMSEETPT 420 FSPDFSSDFENPSPRIFDGFRYLNLRSIKGQGSQHQAATTGPDYLIFNHGKHACPGRFFA 480 ISEIKMILIELLAKYDFRLEDGKPGPELMRVGTETRLDTKAGLEMRRR 528 SEQIDNO:187 atggcggaattagatacgttagatatcgttgttttaggcgctttattgttgggcacatta 60 gcgtattttacgaagggcacattatggggtgtcactaaggatccttatgcaaacgctttc 120 gcaaatgctaacggagctaaagccggcagatcaagaaatatcgttgaaaaaatggatgaa 180 tctggtaaaaactgcgtcatattctacggttctcaaactggaacggcagaggattacgca 240 tcaagattagcgaaagaaggaaagtcaagattcgggttagggactatggttgcagattta 300 gaagaatatgattatgataaccttgatacaatgagcggcgataaggttgccatgtttgtt 360 cttgctacctatggcgagggcgaaccaactgacaacgcagtagagttttatgaatttatt 420 actggtgaaggggttgcttttagtgaaggaaacgatccccccttaggcaatctgaactac 480 gtggcctttggactggggaacaatacttatgaacactacaattcaatggtcagaaatgtc 540 gataaagcccttaggaatctgggtgctcataggatcggagaggctggtgaaggcgatgac 600 ggtgctggcacaatggaagaagattttctagcatggaaggaaccaatgtgggccgcctta 660 gctgacaaaatgggtttggaggaaagggaagcagtatatgaccctgtgttcagtatcgtt 720 gatcgtgataatttgactcctgaaagcccagaagtctatttgggtgaacctaataaaatg 780 catttagaggatgcggtcaagggcccatttaattctcataatccatatatagcaccaata 840 gctgaatctagagaattgtttagtgttaaagacaggaattgcatccatatggaaattgac 900 atagacggttcaaatttgagctatcaaactggggatcatgtggctatttggcctaccaac 960 ccaggagatgaagtggatagatttttagacatcattgatttaaaggataaacgtgacaag 1020 gttataggagtgaaagcacttgaaccaactgcaaaggtcccttttccaacaccaacaaca 1080 tatgacgttatcgccaggtatcatttagaaatctgtgcaccggtctctagacagtttgtg 1140 tccactctagcagcattctccccaaatgatgaggtaaaagcagaaatgactagattgggt 1200 aacgataaggattattttcatgataagacgggcccacattattataatatcgcccgtttt 1260 ctagctgcggttggtaagggcgagaaatggtcaaatatccctttttctgtttttgtcgaa 1320 ggtttaacgaaattacaaccaagatattattcaatctcctcttcaagcctagtacaacca 1380 aaaaaaatatcaataacggcagtaattgagtcacaggttatacctgccaggcaagatcca 1440 tttagaggtgtagctacgaactacttatttgcattgaaacagaagcaaaacggtgatcca 1500 aatccctccccatttggacatacttatgcattaaacggccctagaaataaatttgacggt 1560 atacacgtccccgtccacgtaaggcactccaatttcaaactaccgagcgatccagcaaaa 1620 ccagttattatggttggtccaggaactggagtggctccgtttagaggtttcatccaagag 1680 agagctaaacaggcccaggatggggccacagtaggccgtactatcttgttcttcggttgc 1740 caacgtaggtccgaagattttttgtacgaaagtgaatggaaagaatacaaggaagttcta 1800 ggagatacccttgagatagtcactgccttctccagggaaacatcaaagaaagtttatgtg 1860 cagcacaggttgaaagagagatccaaagaaatcggagaactattatcacagaaagcatac 1920 ttttatgtgtgtggcgatgctgctcatatggctagagaagttaatactgtattggctcaa 1980 attatcgctgaatctaggggtgtaagtgaagccaagggtgaagagattgttaaaaatatg 2040 agggctgctaatcagtaccaagttaggagggggaacaatgtctttttttgggctataagt 2100 ggttctattgatatgacggccaataccgccaacttacaagaagatgtgtggagctga 2157 SEQIDNO:188 MAELDTLDIVVLGALLLGTLAYFTKGTLWGVTKDPYANAFANANGAKAGRSRNIVEKMDE 60 SGKNCVIFYGSQTGTAEDYASRLAKEGKSRFGLGTMVADLEEYDYDNLDTMSGDKVAMFV 120 LATYGEGEPTDNAVEFFEFITGEGVAFSEGNDPPLGNLNYVAFGLGNNTYEHYNSMVRNV 180 DKALRNLGAHRIGEAGEGDDGAGTMEEDFLAWKEPMWAALADKMGLEEREAVYDPVFSIV 240 DRDNLTPESPEVYLGEPNKMHLEDAVKGPFNSHNPYIAPIAESRELFSVKDRNCIHMEID 300 IDGSNLSYQTGDHVAIWPTNPGDEVDRFLDIIDLKDKRDKVIGVKALEPTAKVPFPTPTT 360 YDVIARYHLEICAPVSRQFVSTLAAFSPNDEVKAEMTRLGNDKDYFHDKTGPHYYNIARF 420 LAAVGKGEKWSNIPFSVFVEGLTKLQPRYYSISSSSLVQPKKISITAVIESQVIPARQDP 480 FRGVATNYLFALKQKQNGDPNPSPFGHTYALNGPRNKFDGIHVPVHVRHSNFKLPSDPAK 540 PVIMVGPGTGVAPFRGFIQERAKQAQDGATVGRTILFFGCQRRSEDFLYESEWKEYKEVL 600 GDTLEIVTAFSRETSKKVYVQHRLKERSKEIGELLSQKAYFYVCGDAAHMAREVNTVLAQ 660 IIAESRGVSEAKGEEIVKNMRAANQYQVRRGNNVFFWAISGSIDMTANTANLQEDVWS 718 SEQIDNO:189 atggcggaattagatacgttagatatcgttgttttaggcgctttattgttgggcacatta 60 gcgtattttacgaagggcacattatggggtgtcactaaggatccttatgcaaacgctttc 120 gcaaatgctaacggagctaaagccggcagatcaagaaatatcgttgaaaaaatggatgaa 180 tctggtaaaaactgcgtcatattctacggttctcaaactggaacggcagaggattacgca 240 tcaagattagcgaaagaaggaaagtcaagattcgggttagggactatggttgcagattta 300 gaagaatatgattatgataaccttgatacaatgagcggcgataaggttgccatgtttgtt 360 cttgctacctatggcgagggcgaaccaactgacaacgcagtagagttttatgaatttatt 420 actggtgaaggggttgcttttagtgaaggaaacgatccccccttaggcaatctgaactac 480 gtggcctttggactggggaacaatacttatgaacactacaattcaatggtcagaaatgtc 540 gataaagcccttaggaatctgggtgctcataggatcggagaggctggtgaaggcgatgac 600 ggtgctggcacaatggaagaagattttctagcatggaaggaaccaatgtgggccgcctta 660 gctgacaaaatgggtttggaggaaagggaagcagtatatgaccctgtgttcagtatcgtt 720 gatcgtgataatttgactcctgaaagcccagaagtctatttgggtgaacctaataaaatg 780 catttagaggatgcggtcaagggcccatttaattctcataatccatatatagcaccaata 840 gctgaatctagagaattgtttagtgttaaagacaggaattgcatccatatggaaattgac 900 atagacggttcaaatttgagctatcaaactggggatcatgtggctatttggcctaccaac 960 ccaggagatgaagtggatagatttttagacatcattgatttaaaggataaacgtgacaag 1020 gttataggagtgaaagcacttgaaccaactgcaaaggtcccttttccaacaccaacaaca 1080 tatgacgttatcgccaggtatcatttagaaatctgtgcaccggtctctagacagtttgtg 1140 tccactctagcagcattctccccaaatgatgaggtaaaagcagaaatgactagattgggt 1200 aacgataaggattattttcatgataagacgggcccacattattataatatcgcccgtttt 1260 ctagctgcggttggtaagggcgagaaatggtcaaatatccctttttctgtttttgtcgaa 1320 ggtttaacgaaattacaaccaagatattattcaatctcctcttcaagcctagtacaacca 1380 aaaaaaatatcaataacggcagtaattgagtcacaggttatacctgccaggcaagatcca 1440 tttagaggtgtagctacgaactacttatttgcattgaaacagaagcaaaacggtgatcca 1500 aatccctccccatttggacatacttatgcattaaacggccctagaaataaatttgacggt 1560 atacacgtccccgtccacgtaaggcactccaatttcaaactaccgagcgatccagcaaaa 1620 ccagttattatggttggtccaggaactggagtggctccgtttagaggtttcatccaagag 1680 agagctaaacaggcccaggatggggccacagtaggccgtactatcttgttcttcggttgc 1740 caacgtaggtccgaagattttttgtacgaaagtgaatggaaagaatacaaggaagttcta 1800 ggagatacccttgagatagtcactgccttctccagggaaacatcaaagaaagtttatgtg 1860 cagcacaggttgaaagagagatccaaagaaatcggagaactattatcacagaaagcatac 1920 ttttatgtgtgtggcgatgctgctcatatggctagagaagttaatactgtattggctcaa 1980 attatcgctgaatctaggggtgtaagtgaagccaagggtgaagagattgttaaaaatatg 2040 agggctgctaatcagtaccaagaagatgtgtggagctga 2079 SEQIDNO:190 MAELDTLDIVVLGALLLGTLAYFTKGTLWGVTKDPYANAFANANGAKAGRSRNIVEKMDE 60 SGKNCVIFYGSQTGTAEDYASRLAKEGKSRFGLGTMVADLEEYDYDNLDTMSGDKVAMFV 120 LATYGEGEPTDNAVEFFEFITGEGVAFSEGNDPPLGNLNYVAFGLGNNTYEHYNSMVRNV 180 DKALRNLGAHRIGEAGEGDDGAGTMEEDFLAWKEPMWAALADKMGLEEREAVYDPVFSIV 240 DRDNLTPESPEVYLGEPNKMHLEDAVKGPFNSHNPYIAPIAESRELFSVKDRNCIHMEID 300 IDGSNLSYQTGDHVAIWPTNPGDEVDRFLDIIDLKDKRDKVIGVKALEPTAKVPFPTPTT 360 YDVIARYHLEICAPVSRQFVSTLAAFSPNDEVKAEMTRLGNDKDYFHDKTGPHYYNIARF 420 LAAVGKGEKWSNIPFSVFVEGLTKLQPRYYSISSSSLVQPKKISITAVIESQVIPARQDP 480 FRGVATNYLFALKQKQNGDPNPSPFGHTYALNGPRNKFDGIHVPVHVRHSNFKLPSDPAK 540 PVIMVGPGTGVAPFRGFIQERAKQAQDGATVGRTILFFGCQRRSEDFLYESEWKEYKEVL 600 GDTLEIVTAFSRETSKKVYVQHRLKERSKEIGELLSQKAYFYVCGDAAHMAREVNTVLAQ 660 IIAESRGVSEAKGEEIVKNMRAANQYQEDVWS 692 SEQIDNO:191 atggccgaattggataccttggatatcgttgttttgggtgttatcttcttgggtactgtt 60 gcttacttcaccaaaggtaaattgtggggtgttactaaggatccatacgctaatggtttt 120 gctgctggtggtgcttctaaaccaggtagaactagaaatatcgttgaagccatggaagaa 180 tctggtaagaactgtgttgttttctacggttctcaaactggtactgctgaagattatgct 240 tccagattggctaaagaaggtaagagtagattcggtttgaacaccatgattgccgatttg 300 gaagattacgatttcgataacttggataccgtcccatctgataacatcgttatgtttgtt 360 ttggctacctacggtgaaggtgaacctactgataatgctgttgacttctacgaattcatt 420 accggtgaagatgcttctttcaacgaaggtaatgatccaccattgggtaacttgaattac 480 gttgcttttggtttgggtaacaacacctacgaacattacaactccatggttagaaacgtc 540 aacaaggctttggaaaaattgggtgctcatagaattggtgaagctggtgaaggtgatgat 600 ggtgctggtactatggaagaagattttttggcttggaaagacccaatgtgggaagccttg 660 gctaaaaagatgggtttggaagaaagagaagctgtctacgaacctattttcgccattaac 720 gaaagagatgatttgacccctgaagccaatgaagtttatttgggtgaacctaacaagttg 780 cacttggaaggtactgctaaaggtccattcaattctcacaacccatatattgctccaatc 840 gccgaatcttacgaattattctctgctaaggatagaaactgcttgcacatggaaattgac 900 atctctggttctaatttgaagtacgaaaccggtgatcatattgccatttggccaactaat 960 ccaggtgaagaagttaacaagttcttggacatcttggacttgtccggtaaacaacattct 1020 gttgttactgttaaggccttggaacctacagctaaagttccttttccaaatccaactacc 1080 tacgatgccattttgagataccatttggaaatttgcgctccagtctctagacaattcgtt 1140 tctactttggctgcttttgctccaaacgatgatattaaggctgaaatgaacagattgggt 1200 tccgataaggattacttccacgaaaaaactggtccacactactacaacattgctagattt 1260 ttggcctctgtctctaaaggtgaaaagtggactaagattccattctccgctttcattgaa 1320 ggtttgactaagttgcaacctagatattactccatctcctcctcatctttggttcaacct 1380 aagaagatctctattaccgccgttgttgaatcccaacaaattccaggtagagatgatcct 1440 tttagaggtgttgctaccaattacttgttcgccttgaaacaaaagcaaaacggtgatcca 1500 aatcctgctccatttggtcaatcttatgaattgactggtccaagaaacaagtacgatggt 1560 attcatgttccagttcacgttagacactctaactttaagttgccatctgatccaggtaag 1620 ccaattatcatgattggtccaggtactggtgttgctccattcagaggttttgttcaagaa 1680 agagctaagcaagctagagatggtgttgaagttggtaaaaccttgttgttcttcggttgt 1740 agaaagtccactgaagatttcatgtaccaaaaagaatggcaagaatacaaagaagcctta 1800 ggtgacaagttcgaaatgattactgccttctcaagagaaggttctaagaaggtttacgtc 1860 caacacagattgaaagaaagatccaaagaagtctccgatttgttgtctcaaaaggcctac 1920 ttttacgtttgtggtgatgctgctcatatggccagagaagttaatactgttttggcccaa 1980 attatcgctgaaggtagaggtgtatctgaagctaagggtgaagaaatcgttaagaacatg 2040 agatccgccaatcaataccaagaagatgtttggtcctaa 2079 SEQIDNO:192 MAELDTLDIVVLGVIFLGTVAYFTKGKLWGVTKDPYANGFAAGGASKPGRTRNIVEAMEE 60 SGKNCVVFYGSQTGTAEDYASRLAKEGKSRFGLNTMIADLEDYDFDNLDTVPSDNIVMFV 120 LATYGEGEPTDNAVDFYEFITGEDASFNEGNDPPLGNLNYVAFGLGNNTYEHYNSMVRNV 180 NKALEKLGAHRIGEAGEGDDGAGTMEEDFLAWKDPMWEALAKKMGLEEREAVYEPIFAIN 240 ERDDLTPEANEVYLGEPNKLHLEGTAKGPFNSHNPYIAPIAESYELFSAKDRNCLHMEID 300 ISGSNLKYETGDHIAIWPTNPGEEVNKFLDILDLSGKQHSVVTVKALEPTAKVPFPNPTT 360 YDAILRYHLEICAPVSRQFVSTLAAFAPNDDIKAEMNRLGSDKDYFHEKTGPHYYNIARF 420 LASVSKGEKWTKIPFSAFIEGLTKLQPRYYSISSSSLVQPKKISITAVVESQQIPGRDDP 480 FRGVATNYLFALKQKQNGDPNPAPFGQSYELTGPRNKYDGIHVPVHVRHSNFKLPSDPGK 540 PIIMIGPGTGVAPFRGFVQERAKQARDGVEVGKTLLFFGCRKSTEDFMYQKEWQEYKEAL 600 GDKFEMITAFSREGSKKVYVQHRLKERSKEVSDLLSQKAYFYVCGDAAHMAREVNTVLAQ 660 IIAEGRGVSEAKGEEIVKNMRSANQYQEDVWS 692 SEQIDNO:193 atggcagaattagatacacttgatatagtagtattaggtgttatctttttgggtactgtg 60 gcatactttactaagggtaaattgtggggtgttaccaaggatccatacgctaacggattc 120 gctgcaggtggtgcttccaagcctggcagaactagaaacatcgtcgaagctatggaggaa 180 tcaggtaaaaactgtgttgttttctacggcagtcaaacaggtacagcggaggattacgca 240 tcaagacttgcaaaggaaggaaagtccagattcggtttgaacactatgatcgccgatcta 300 gaagattatgacttcgataacttagacactgttccatctgataacatcgttatgtttgta 360 ttggctacttacggtgaaggcgaaccaacagataacgccgtggatttctatgagttcatt 420 actggcgaagatgcctctttcaatgagggcaacgatcctccactaggtaacttgaattac 480 gttgcgttcggtctgggcaacaatacctacgaacactacaactcaatggtcaggaacgtt 540 aacaaggctctagaaaagttaggagctcatagaattggagaagcaggtgagggtgacgac 600 ggagctggaactatggaagaggactttttagcttggaaagatccaatgtgggaagccttg 660 gctaaaaagatgggcttggaggaaagagaagctgtatatgaacctattttcgctatcaat 720 gagagagatgatttgacccctgaagcgaatgaggtatacttgggagaacctaataagcta 780 cacttggaaggtacagcgaaaggtccattcaactcccacaacccatatatcgcaccaatt 840 gcagaatcatacgaacttttctcagctaaggatagaaattgtctgcatatggaaattgat 900 atttctggtagtaatctaaagtatgaaacaggcgaccatatcgcgatctggcctaccaac 960 ccaggtgaagaggtcaacaaatttcttgacattctagatctgtctggtaagcaacattcc 1020 gtcgtaacagtgaaagccttagaacctacagccaaagttccttttccaaatccaactacc 1080 tacgatgctatattgagataccatctggaaatatgcgctccagtttctagacagtttgtc 1140 tcaactttagcagcattcgcccctaatgatgatatcaaagctgagatgaaccgtttggga 1200 tcagacaaagattacttccacgaaaagacaggaccacattactacaatatcgctagattt 1260 ttggcctcagtctctaaaggtgaaaaatggacaaagataccattttctgctttcatagaa 1320 ggccttacaaaactacaaccaagatactattctatctcttcctctagtttagttcagcct 1380 aaaaagattagtattactgctgttgtcgaatctcagcaaattccaggtagagatgaccca 1440 ttcagaggtgtagcgactaactacttgttcgctttgaagcagaaacaaaacggtgatcca 1500 aatccagctccttttggccaatcatacgagttgacaggaccaaggaataagtatgatggt 1560 atacatgttccagtccatgtaagacattctaactttaagctaccatctgatccaggcaaa 1620 cctattatcatgatcggtccaggtaccggtgttgccccttttagaggcttcgtccaagag 1680 agggcaaaacaagccagagatggtgtagaagttggtaaaacactgctgttctttggatgt 1740 agaaagagtacagaagatttcatgtatcaaaaagagtggcaagagtacaaggaagctctt 1800 ggcgacaaattcgaaatgattacagctttttcaagagaaggatctaaaaaggtttatgtt 1860 caacacagactgaaggaaagatcaaaggaagtttctgatcttctatcccaaaaagcatac 1920 ttctacgtttgcggagacgccgcacatatggcacgtgaagtgaacactgtgttagcacag 1980 atcatagcagaaggccgtggtgtatcagaagccaagggtgaggaaattgtcaaaaacatg 2040 agatcagcaaatcaataccaagaggatgtctggagttaa 2079 SEQIDNO:194 MAELDTLDIVVLGVIFLGTVAYFTKGKLWGVTKDPYANGFAAGGASKPGRTRNIVEAMEE 60 SGKNCVVFYGSQTGTAEDYASRLAKEGKSRFGLNTMIADLEDYDFDNLDTVPSDNIVMFV 120 LATYGEGEPTDNAVDFYEFITGEDASFNEGNDPPLGNLNYVAFGLGNNTYEHYNSMVRNV 180 NKALEKLGAHRIGEAGEGDDGAGTMEEDFLAWKDPMWEALAKKMGLEEREAVYEPIFAIN 240 ERDDLTPEANEVYLGEPNKLHLEGTAKGPFNSHNPYIAPIAESYELFSAKDRNCLHMEID 300 ISGSNLKYETGDHIAIWPTNPGEEVNKFLDILDLSGKQHSVVTVKALEPTAKVPFPNPTT 360 YDAILRYHLEICAPVSRQFVSTLAAFAPNDDIKAEMNRLGSDKDYFHEKTGPHYYNIARF 420 LASVSKGEKWTKIPFSAFIEGLTKLQPRYYSISSSSLVQPKKISITAVVESQQIPGRDDP 480 FRGVATNYLFALKQKQNGDPNPAPFGQSYELTGPRNKYDGIHVPVHVRHSNFKLPSDPGK 540 PIIMIGPGTGVAPFRGFVQERAKQARDGVEVGKTLLFFGCRKSTEDFMYQKEWQEYKEAL 600 GDKFEMITAFSREGSKKVYVQHRLKERSKEVSDLLSQKAYFYVCGDAAHMAREVNTVLAQ 660 IIAEGRGVSEAKGEEIVKNMRSANQYQEDVWS 692 SEQIDNO:195 atggcttcagaaaaagaaattaggagagagagattcttgaacgttttccctaaattagta 60 gaggaattgaacgcatcgcttttggcttacggtatgcctaaggaagcatgtgactggtat 120 gcccactcattgaactacaacactccaggcggtaagctaaatagaggtttgtccgttgtg 180 gacacgtatgctattctctccaacaagaccgttgaacaattggggcaagaagaatacgaa 240 aaggttgccattctaggttggtgcattgagttgttgcaggcttacttcttggtcgccgat 300 gatatgatggacaagtccattaccagaagaggccaaccatgttggtacaaggttcctgaa 360 gttggggaaattgccatcaatgacgcattcatgttagaggctgctatctacaagcttttg 420 aaatctcacttcagaaacgaaaaatactacatagatatcaccgaattgttccatgaggtc 480 accttccaaaccgaattgggccaattgatggacttaatcactgcacctgaagacaaagtc 540 gacttgagtaagttctccctaaagaagcactccttcatagttactttcaagactgcttac 600 tattctttctacttgcctgtcgcattggccatgtacgttgccggtatcacggatgaaaag 660 gatttgaaacaagccagagatgtcttgattccattgggtgaatacttccaaattcaagat 720 gactacttagactgcttcggtaccccagaacagatcggtaagatcggtacagatatccaa 780 gataacaaatgttcttgggtaatcaacaaggcattggaacttgcttccgcagaacaaaga 840 aagactttagacgaaaattacggtaagaaggactcagtcgcagaagccaaatgcaaaaag 900 attttcaatgacttgaaaattgaacagctataccacgaatatgaagagtctattgccaag 960 gatttgaaggccaaaatttctcaggtcgatgagtctcgtggcttcaaagctgatgtctta 1020 actgcgttcttgaacaaagtttacaagagaagcaaaggttctagtactggttcatctaca 1080 tctactggaggtatggtcgcacaaactttcaacctggatacctacttatcccaaagacaa 1140 caacaagttgaagaggccctaagtgctgctcttgtgccagcttatcctgagagaatatac 1200 gaagctatgagatactccctcctggcaggtggcaaaagattaagacctatcttatgttta 1260 gctgcttgcgaattggcaggtggttctgttgaacaagccatgccaactgcgtgtgcactt 1320 gaaatgatccatacaatgtcactaattcatgatgacctgccagccatggataacgatgat 1380 ttcagaagaggaaagccaactaatcacaaggtgttcggggaagatatagccatcttagcg 1440 ggtgatgcgcttttagcttacgcttttgaacatattgcttctcaaacaagaggagtacca 1500 cctcaattggtgctacaagttattgctagaatcggacacgccgttgctgcaacaggcctc 1560 gttggaggccaagtcgtagaccttgaatctgaaggtaaagctatttccttagaaacattg 1620 gagtatattcactcacataagactggagccttgctggaagcatcagttgtctcaggcggt 1680 attctcgcaggggcagatgaagagcttttggccagattgtctcattacgctagagatata 1740 ggcttggcttttcaaatcgtcgatgatatcctggatgttactgctacatctgaacagttg 1800 gggaaaaccgctggtaaagaccaggcagccgcaaaggcaacttatccaagtctattgggt 1860 ttagaagcctctagacagaaagcggaagagttgattcaatctgctaaggaagccttaaga 1920 ccttacggttcacaagcagagccactcctagcgctggcagacttcatcacacgtcgtcag 1980 cattaa 1986 SEQIDNO:196 MASEKEIRRERFLNVFPKLVEELNASLLAYGMPKEACDWYAHSLNYNTPGGKLNRGLSVV 60 DTYAILSNKTVEQLGQEEYEKVAILGWCIELLQAYFLVADDMMDKSITRRGQPCWYKVPE 120 VGEIAINDAFMLEAAIYKLLKSHFRNEKYYIDITELFHEVTFQTELGQLMDLITAPEDKV 180 DLSKFSLKKHSFIVTFKTAYYSFYLPVALAMYVAGITDEKDLKQARDVLIPLGEYFQIQD 240 DYLDCFGTPEQIGKIGTDIQDNKCSWVINKALELASAEQRKTLDENYGKKDSVAEAKCKK 300 IFNDLKIEQLYHEYEESIAKDLKAKISQVDESRGFKADVLTAFLNKVYKRSKGSSTGSST 360 STGGMVAQTFNLDTYLSQRQQQVEEALSAALVPAYPERIYEAMRYSLLAGGKRLRPILCL 420 AACELAGGSVEQAMPTACALEMIHTMSLIHDDLPAMDNDDFRRGKPTNHKVFGEDIAILA 480 GDALLAYAFEHIASQTRGVPPQLVLQVIARIGHAVAATGLVGGQVVDLESEGKAISLETL 540 EYIHSHKTGALLEASVVSGGILAGADEELLARLSHYARDIGLAFQIVDDILDVTATSEQL 600 GKTAGKDQAAAKATYPSLLGLEASRQKAEELIQSAKEALRPYGSQAEPLLALADFITRRQ 660 H 661 SEQIDNO:197 atgccaaagattGttattttgcctcatcaggatctctgccctgatggcgctgttctggaa 60 gctaatagcggtgaaaccattctcgacgcagctctgcgtaacggtatcgagattgaacac 120 gcctgtgaaaaatcctgtgcttgcaccacctgccactgcatcgttcgtgaaggttttgac 180 tcactgccggaaagctcagagcaggaagacgacatgctggacaaagcctggggactggag 240 ccggaaagccgtttaagctgccaggcgcgcgttaccgacgaagatttagtagtcgaaatc 300 ccgcgttacactatcaaccatgcgcgtgagcattaa 336 SEQIDNO:198 MPKIVILPHQDLCPDGAVLEANSGETILDAALRNGIEIEHACEKSCACTTCHCIVREGFD 60 SLPESSEQEDDMLDKAWGLEPESRLSCQARVTDEDLVVEIPRYTINHAREH 111 SEQIDNO:199 atggctgattgggtaacaggcaaagtcactaaagtgcagaactggaccgacgccctgttt 60 agtctcaccgttcacgcccccgtgcttccgtttaccgccgggcaatttaccaagcttggc 120 cttgaaatcgacggcgaacgcgtccagcgcgcctactcctatgtaaactcgcccgataat 180 cccgatctggagttttacctggtcaccgtccccgatggcaaattaagcccacgactggcg 240 gcactgaaaccaggcgatgaagtgcaggtggttagcgaagcggcaggattctttgtgctc 300 gatgaagtgccgcactgcgaaacgctatggatgctggcaaccggtacagcgattggccct 360 tatttatcgattctgcaactaggtaaagatttagatcgcttcaaaaatctggtcctggtg 420 cacgccgcacgttatgccgccgacttaagctatttgccactgatgcaggaactggaaaaa 480 cgctacgaaggaaaactgcgcattcagacggtggtcagtcgggaaacggcagcggggtcg 540 ctcaccggacggataccggcattaattgaaagtggggaactggaaagcacgattggcctg 600 ccgatgaataaagaaaccagccatgtgatgctgtgcggcaatccacagatggtgcgcgat 660 acacaacagttgctgaaagagacccggcagatgacgaaacatttacgtcgccgaccgggc 720 catatgacagcggagcattactggtaa 747 SEQIDNO:200 MADWVIGKVTKVQNWTDALFSLTVHAPVLPFTAGQFTKLGLEIDGERVQRAYSYVNSPDN 60 PDLEFYLVTVPDGKLSPRLAALKPGDEVQVVSEAAGFFVLDEVPHCETLWMLATGTAIGP 120 YLSILQLGKDLDRFKNLVLVHAARYAADLSYLPLMQELEKRYEGKLRIQTVVSRETAAGS 180 LTGRIPALIESGELESTIGLPMNKETSHVMLCGNPQMVRDTQQLLKETRQMTKHLRRRPG 240 HMTAEHYW 248 SEQIDNO:201 atgtccttcccagatgaacaaaaggttgatttccaaaccttccagaacgttatcaacaat 60 caattgtctccaacctccgaatccagacatggtatttgtccatctactgaagaatccttg 120 tgggaatctccagtttctactcaagatgatgttgatagagctgtttctgctgctaaagct 180 gcttatccagcttggagaaaattgtcttgggacgaaagagcttcttacttggttaagttt 240 gctgatgctattgaagcccacaagcaagaattcattgatttgttgggtagagaagctggt 300 aaaccaccacaagctggtggttttgaattgatgttggttatggaacacgttagggaaact 360 ccaaagttgagaattggtgaagttaagccagaagataacgaagatagaaccgctgttgtt 420 agatacgttccaattggtgttggtgttggtatagttccatggaattttccaatgttgttg 480 ggtattggtaaagcttacccagctatgttggctggtaatacttttatttggaagccatct 540 ccatacaccccatactctgctttgaaattggctgaaattggtgctaaagttttgccacca 600 ggtgttttacaagctttgtctggtggtgatgatttgggtccaatgttgactgctcatcca 660 gatgttgccaaagtttcttttactggttctactgaaaccggtaaaaagattatggctgct 720 tgtgctgctactttgaagagagttactttggaattgggtggtaatgatgctgctatcgtt 780 tgtgaagatgttgatattccaggtgttgctggtaaggttgcttttttggcttatgttcat 840 tctggtcagatctgcatgaacatcaagagaatctacgttcacgaatccatctacgacaag 900 ttcgtttccgaagttatcaagttcttgcatgctttgaaaaccggtgatttctctgatcca 960 gaagctttttttggtccaatccaaaacaagatgcagtacgaaaaattgcagaggttgtac 1020 gaacaaatcgataagcaaggttggaagtgtgcttttggttctgcttctccagctacttct 1080 gaaaaaggttattttgttccaccagtcttggttgataatccaccagaagattctgaaatc 1140 gtccaaatggaaccatttggtccaatagttccagttatgaagtggcaatctgaagatgat 1200 gttattgctagagctaacgcttctgattatggtttgggtgcttctgtttggtctaaagat 1260 gttgctagagcaagaagaatggctgaattattggaagctggttctgtttgggttaacacc 1320 cattttgaagttgctccaaatgttccttttggtggtcataagcaatctggtattggtatg 1380 gattggggtgaagttggtttgaaaggttggtgtaatccacaagcttattgggtcaaacat 1440 tccggttaa 1449 SEQIDNO:202 MSFPDEQKVDFQTFQNVINNQLSPTSESRHGICPSTEESLWESPVSTQDDVDRAVSAAKA 60 AYPAWRKLSWDERASYLVKFADAIEAHKQEFIDLLGREAGKPPQAGGFELMLVMEHVRET 120 PKLRIGEVKPEDNEDRTAVVRYVPIGVGVGIVPWNFPMLLGIGKAYPAMLAGNTFIWKPS 180 PYTPYSALKLAEIGAKVLPPGVLQALSGGDDLGPMLTAHPDVAKVSFTGSTETGKKIMAA 240 CAATLKRVILELGGNDAAIVCEDVDIPGVAGKVAFLAYVHSGQICMNIKRIYVHESIYDK 300 FVSEVIKFLHALKTGDFSDPEAFFGPIQNKMQYEKLQRLYEQIDKQGWKCAFGSASPATS 360 EKGYFVPPVLVDNPPEDSEIVQMEPFGPIVPVMKWQSEDDVIARANASDYGLGASVWSKD 420 VARARRMAELLEAGSVWVNTHFEVAPNVPFGGHKQSGIGMDWGEVGLKGWCNPQAYWVKH 480 SG 482 SEQIDNO:205 atgtggtggctgtttcgtgccttgttttcatcaattttcctgctttcaatcgttttaagt 60 attcctgttgcttttgatgttggtgggagagattcaggacttgcctatagtttagctttg 120 ttcttattctacttcatctactctagtttagaacttcttacgcctgaaaagtccagaagt 180 cgttatttcttatctggcttcttaagattgagccaatggattatcatacctgcactatta 240 atttgggcgttaggtcagttcgcggttgacgcagataacaccaattgggttgaacgtacc 300 gttggaggtctgttcaattccaaatccacctcttggagagaatggatgtttggcaaggat 360 ggactggtggaaactatcactttaggcggctgggataacttgttacgttattctggtcca 420 gtgttccaattattagagggattttgtacacttcttgtaatccaagctgccggacaatta 480 accagatggcttgtaaatagaggtcgttcagatacatggctaattgtattgttagtgtta 540 agctcaagtatcatggcatcagctgtgtattttctttggcgtgttgcacagtttccccag 600 atcgggaatctagacgcaacgttaataggtattgcgatgacaaccgcagtatttttgtgt 660 gcgttcggcatcggttctggcaggggtaatcccattgaatcatcattgttgttcgcttac 720 attgtcttgtgtatttaccaaatttttacagactatctaccatcagaaaatgcagaccac 780 acgcaagatcatgatggctcagaaagcgatatccctcctcttcctcctgttatcatggct 840 agctacagcacgttccttcatatgttgggctctttgccctctgccgttcattcatcattg 900 gcacttttgtatgctgccttccagactataactccatccgtaattatttcactaacctat 960 aggagtcttgttttttactgcgccactaggattatacctagcattagagaaagtggtgca 1020 caggctatgatgcaagaaccagactgggaagatagcgaaacagcttctaaatttttgggc 1080 tttttgagctggttttccccctctatcttgatagctgtgtatacctccttattacttcaa 1140 catttttctacgagtgatggtcctgatggttggacgttgagaggcggagatgttgagggt 1200 tctaattggcaatgggccaacataggtcttaccatggttttgtacggagtcgaactgtac 1260 ctgggctctgatgagcatgatcattggaaggtggattaa 1299 SEQIDNO:206 MWWLFRALFSSIFLLSIVLSIPVAFDVGGRDSGLAYSLALFLFYFIYSSLELLTPEKSRS 60 RYFLSGFLRLSQWIIIPALLIWALGQFAVDADNTNWVERTVGGLFNSKSTSWREWMFGKD 120 GLVETITLGGWDNLLRYSGPVFQLLEGFCTLLVIQAAGQLTRWLVNRGRSDTWLIVLLVL 180 SSSIMASAVYFLWRVAQFPQIGNLDATLIGIAMITAVELCAFGIGSGRGNPIESSLLFAY 240 IVLCIYQIFTDYLPSENADHTQDHDGSESDIPPLPPVIMASYSTFLHMLGSLPSAVHSSL 300 ALLYAAFQTITPSVIISLTYRSLVFYCATRIIPSIRESGAQAMMQEPDWEDSETASKFLG 360 FLSWFSPSILIAVYTSLLLQHFSTSDGPDGWTLRGGDVEGSNWQWANIGLTMVLYGVELY 420 LGSDEHDHWKVD 432 SEQIDNO:207 atggctgattctacattagctgctaacggtaacagtttattggaaactacaaaaacaaat 60 gcggcagctgcctaccaaagcgttgcgaacggacccgttgcacagaatgtatacgatcac 120 acgcaaaaggcatccaatgagttgtctaatctagcagctgcaaggagaactccggctaat 180 ccagccgctacaggtcaaccattgacgcattatcattcttttttcagtgaattactgagt 240 tggaataacccaagagcttctgccatagcttacgttacaattattggtgccatttttacg 300 gctagatatcttgatttgttgagatggggattgaaagtttcttggatggttttgggtgtt 360 actattcttgccgaggtattgggcaaggtaattctaaacaatggactggccacccaagtc 420 agacctaggaggtattatacagtacctagagaaacactagatgctctaatcggcgatgtt 480 catgaactaattaattttttcgtcatcgaagcacaacgtatcatttttgcagaaaacgtc 540 tttgcaagtgcggctgcctttattgctgcttttatatcttattttttggtgaaattagtt 600 ccctactggggactagcagttattggtaccactgttgccttcgttgtcccattaatatac 660 acctcaaatcaagaattgatcgacgaacaactacaccatgctagtgaactaataaatagc 720 caaacagcgcaaatacaatccgttgcatctaaacaaatggaacaagtttccaatatctcc 780 aaacaatatgcaggagattatagtggtaaagtgcaagacctgttaagaggaaagacgcct 840 agcaggcagaagatagacaagcccgagcaaccaattagcgctaaacaaccccaattcccc 900 agtccaccaaccgaggatccggtgacagcaacggaagctcctcaaatacctacccccgct 960 gcgcttaaggaagagcttaatgctccaaccgcaatcgatactgctgcacctgaattaccc 1020 catgaggatgttgtgccctcaaaagaacctatgttagcctcctaa 1065 SEQIDNO:208 MADSTLAANGNSLLETTKTNAAAAYQSVANGPVAQNVYDHTQKASNELSNLAAARRTPAN 60 PAATGQPLTHYHSFFSELLSWNNPRASAIAYVTIIGAIFTARYLDLLRWGLKVSWMVLGV 120 TILAEVLGKVILNNGLATQVRPRRYYTVPRETLDALIGDVHELINFFVIEAQRIIFAENV 180 FASAAAFIAAFISYFLVKLVPYWGLAVIGTTVAFVVPLIYTSNQELIDEQLHHASELINS 240 QTAQIQSVASKQMEQVSNISKQYAGDYSGKVQDLLRGKTPSRQKIDKPEQPISAKQPQFP 300 SPPTEDPVTATEAPQIPTPAALKEELNAPTAIDTAAPELPHEDVVPSKEPMLAS 354 SEQIDNO:209 MTERELHADVRRFYQHTSQTLTGLRPYPTEREVQDAAAAWQQKDNIENAIREAVRKGSPD 60 SGGITDIVIPLSAAEKRALINEIDHSFSENGMWMVIFTVSLSAFLQGFVQSSQNGANLFA 120 DQWLKSQKHTVNSQFAYANAAVYFSAAVIGCPLAAPMSSLFGRRGVIIVASFLIFAASVG 180 SACITLNDNAWLSLRSIRLIGGVGMGLKATSTPILAAETAVGSWRGSSVLLWQLWVSFGI 240 MMSFIVNICLNQIDDKNLKLRLILASPAVFALMLMYTVAKCPESFRYYLMPGSRKYSPEK 300 AYASLLRLRNTKVGHNTSTHPFWLTPSFPFTICTVEQHLIQAVTATSSQRLVLDAAPKPR 360 TLVVGAVSHYVRQYWKILKVHRLRNAAITTGIVALSQQLSGINLMAFYGGTTLVGISPGN 420 QPTEDQISKAMLYNLIFGLSNFLFCLPAIHSIDVLGRRRVLLFTIPGMALTLMAAAISFN 480 TANEDVRNGLVAFWIYFHTVFYSPGMGPVPFVLASESFPLAFRDTGASLAISINLLFAGL 540 LAWLQPLLVTGIRFGGILGVFAGLNVVAFALIFLLMEETSGVPLESLGSVFDQSKKDLIH 600 FQLFKFLPWFGRFILGRSSLAERPERTVDLSPSSVTAASVTDDDDEERIWNSDTVSSGVR 660 LADMLGGNGRG 671 SEQIDNO:210 MSSPLDAAGLAIATTELCRNLATGLYFIIREIRDASKDAEIMQDTLAALHTRLDQVRALF 60 DANVPQSPLEKDYRNSIDRTLENIHRDLSLLTSKLHIDVILEAKGSKRLEAWYVLQRKFQ 120 SDDIRNIKQRLAGSEELLQSHFEMLSIYISYRIRDEVIDFKAFVRPILEKLLFHATLTEE 180 RQRYQAAESRSIKRLQHVTNALGTGNTFPGEESDFEYHDAFKTWKDKSEAMIMSIADPPW 240 HQVSNSNYVPSIRNESRDGASILPTVRDFREKNGMYPSLRVTPNLSHVEEILDESLHQDV 300 TEDLINWCKEQGFPVNVSNFRYDLIWEAAPVALKGTSPMHQAIKTNNMVVLEKMLSRDCN 360 IEVRLEDGSQDPTPLLLAGSELNAVAVKLLLTKGAKADATDRIGKTGLHLCQSPKFEGRR 420 VAKLLLGDSRAEALDVNAQDQFGMTAAHIAARVGDVKMLEYLLLDQYGKKVADANAQQQD 480 GSTPLMVALKSNIANKKQVIDVLSRCSDLSIKNKNGEDAKEVAAKHSPKDVRKYLLAHLD 540 QDSTRSRRISESTIVVSGISVQMREESCSGCRRHCPQFTDCKLSIGDSAFSQDWKRSLRK 600 YSSDQSSIAMGSSSSIRQAR 620 SEQIDNO:211 MSGRESIAAAPLPEPEPYSVFDKRQTALIVTIVSIAATFSGFASNIYFPALPTIAKDLNV 60 SIELINLTVTSYLIFQGLAPSLWGPISDVKGRRVAYLLTFIVFLGACIGLAEAKNYATMV 120 VLRCVQSTGSASTIAIGSGVIGDITTRDNRGGLMGIFQAGLLVPVAVGPIIGGALAGSLG 180 WRSIFWFLTIYSGVFLIFLVLLLPETLRSIVGNGSREPKHVMAKYPLRVYQKTTKVKWIH 240 DATSPSPTEKKRIDITGPFRILISKQAAPIIVFLAVYYAVWQMSITAMSSLFKDKYGLTE 300 TEIGLTFIANGVGSMVGTLITGKILNMDYRRFKARHDARIASGSKENDVETVNTRKNQEN 360 DFPLETARLRLVPVFSLLQCASILLFGWTIQYPKQVHIAVPIISTFITGWSAVSMQSVVM 420 TYLVDVFHDRSAAASASLNLARCLFAAGGTSFVMPLINSIGVGLAFTVCVVVQGVALVSL 480 AVQWKLGAKWRREAEDARSEP 501 SEQIDNO:212 atgttacgttcatctcctccaccaagcctgcccagagacgccccaagcactgtttttaaa 60 acttatacaccacacacgttgttaccatttaacggagaagaggaccgtcctgtttttctg 120 gccgttagaggcagagtctttgatgtgtcccctggcagaaatttttatggtccaggaggt 180 ccctactctaattttgctggtcgtgatgcatctagagggttagcctgtggtagcttcgat 240 gaagatatgttgaccaaggatctagatggcccactagataaactagaaggtttagacgcg 300 gaacaaatggaagctttacaaggatgggaggaaagatttctggaaaaatacaatgtcgtg 360 ggtaaacttgtttctgttcaggattatgaatctcagaaggcttaa 405 SEQIDNO:213 MLRSSPPPSLPRDAPSTVFKTYTPHTLLPFNGEEDRPVFLAVRGRVFDVSPGRNFYGPGG 60 PYSNFAGRDASRGLACGSFDEDMLTKDLDGPLDKLEGLDAEQMEALQGWEERFLEKYNVV 120 GKLVSVQDYESQKA 134 SEQIDNO:214 atggagcatgttgaacaacacatggctcaacaagcttcccaagaaacagcgtcattgttc 60 acaccattaaacttaattttgctgtctgctgttttatacaccacttattccatgttacgt 120 tcatctcctccaccaagcctgcccagagacgccccaagcactgtttttaaaacttataca 180 ccacacacgttgttaccatttaacggagaagaggaccgtcctgtttttctggccgttaga 240 ggcagagtctttgatgtgtcccctggcagaaatttttatggtccaggaggtccctactct 300 aattttgctggtcgtgatgcatctagagggttagcctgtggtagcttcgatgaagatatg 360 ttgaccaaggatctagatggcccactagataaactagaaggtttagacgcggaacaaatg 420 gaagctttacaaggatgggaggaaagatttctggaaaaatacaatgtcgtgggtaaactt 480 gtttctgttcaggattatgaatctcagaaggcttaa 516 SEQIDNO:215 MEHVEQHMAQQASQETASLFTPLNLILLSAVLYTTYSMLRSSPPPSLPRDAPSTVFKTYT 60 PHTLLPFNGEEDRPVFLAVRGRVFDVSPGRNFYGPGGPYSNFAGRDASRGLACGSFDEDM 120 LTKDLDGPLDKLEGLDAEQMEALQGWEERFLEKYNVVGKLVSVQDYESQKA 171 SEQIDNO:216 atggctggcaagttcgaacccaaagtgcccgttaatttggacccacctaaagatgacata 60 atctcaagggaagagttagcaaaggcaaacggtgctgatgggaataagtgttatgttgca 120 attaaaggcaaggtgtatgacgtaaccggcaacaaagcctacttgccaggcgcaagctat 180 aatgtgtttgctggcaaagatgcctcaagagctttgggtaaaaccagcaccaaacctgag 240 gatgctaggcctgaatggcaagacttagatgagaaagaaaagggtgtcttaaacgactgg 300 attactttctttagcaaaagatacaatgttgtgggggttgtggaaggcgcaacaaacatg 360 gattag 366 SEQIDNO:217 MAGKFEPKVPVNLDPPKDDIISREELAKANGADGNKCYVAIKGKVYDVTGNKAYLPGASY 60 NVFAGKDASRALGKTSTKPEDARPEWQDLDEKEKGVLNDWITFFSKRYNVVGVVEGATNM 120 D 121 SEQIDNO:218 atggctgacgaatcaacacttcgtcaaagaaaaccgcaaccgaagaacgaaaccgaaagt 60 gaagtttctcgtcctagcacacctactaaaaaatcaaaaaagagatcatccgcaaaagtt 120 gacgaggaagatccatgggatggttattccccatacttagatgtggtgagagtaattagc 180 tttattattgttgcatctatgggattgagctatgtcatttcaggtggcgagtcattctgg 240 tggggtcataaaaacaagccgaattggatgacacaacgtttctacaaagatttgatatta 300 ggacccccacctccagtgtacatgactttggaggaactttctttacatgacggtactgat 360 cctgacagaccgcttttacttgcgatcaacggtacaatttatgacgtgtcaaatggtagg 420 agaatgtacggcccaggtggttcctattcttactttgcagctacggatgctgcaagggga 480 ttcgtcaccggctgttttgctgaagatcaaactgcagacttgagaggttatgaagaaact 540 tttcttccactggacgatccagaagttgacagtcactggactcccgaagctctggcagaa 600 ctgaagatcaaagagcgtgaagaagctaaaaaaagggctgatgctgctttacaacactgg 660 gttgatttttttgcaaattccaaaaaatacaccaaagtcggttatgtttatagagagccg 720 gggtggcttgaaaaagagaaaccaaagaaattatgcgatcaggcccaaagatcaagaaag 780 accagaaaaattccaaaaaaggattaa 807 SEQIDNO:219 MADESTLRQRKPQPKNETESEVSRPSTPTKKSKKRSSAKVDEEDPWDGYSPYLDVVRVIS 60 FIIVASMGLSYVISGGESFWWGHKNKPNWMTQRFYKDLILGPPPPVYMTLEELSLHDGTD 120 PDRPLLLAINGTIYDVSNGRRMYGPGGSYSYFAATDAARGFVTGCFAEDQTADLRGYEET 180 FLPLDDPEVDSHWTPEALAELKIKEREEAKKRADAALQHWVDFFANSKKYTKVGYVYREP 240 GWLEKEKPKKLCDQAQRSRKTRKIPKKD 268 SEQIDNO:220 atggcttcagaaaaagaaattaggagagagagattcttgaacgttttccctaaattagta 60 gaggaattgaacgcatcgcttttggcttacggtatgcctaaggaagcatgtgactggtat 120 gcccactcattgaactacaacactccaggcggtaagctaaatagaggtttgtccgttgtg 180 gacacgtatgctattctctccaacaagaccgttgaacaattggggcaagaagaatacgaa 240 aaggttgccattctaggttggtgcattgagttgttgcaggcttacttcttggtcgccgat 300 gatatgatggacaagtccattaccagaagaggccaaccatgttggtacaaggttcctgaa 360 gttggggaaattgccatcaatgacgcattcatgttagaggctgctatctacaagcttttg 420 aaatctcacttcagaaacgaaaaatactacatagatatcaccgaattgttccatgaggtc 480 accttccaaaccgaattgggccaattgatggacttaatcactgcacctgaagacaaagtc 540 gacttgagtaagttctccctaaagaagcactccttcatagttactttcaagactgcttac 600 tattctttctacttgcctgtcgcattggccatgtacgttgccggtatcacggatgaaaag 660 gatttgaaacaagccagagatgtcttgattccattgggtgaatacttccaaattcaagat 720 gactacttagactgcttcggtaccccagaacagatcggtaagatcggtacagatatccaa 780 gataacaaatgttcttgggtaatcaacaaggcattggaacttgcttccgcagaacaaaga 840 aagactttagacgaaaattacggtaagaaggactcagtcgcagaagccaaatgcaaaaag 900 attttcaatgacttgaaaattgaacagctataccacgaatatgaagagtctattgccaag 960 gatttgaaggccaaaatttctcaggtcgatgagtctcgtggcttcaaagctgatgtctta 1020 actgcgttcttgaacaaagtttacaagagaagcaaaggttctagtactggttcatctaca 1080 tctactggaatggtcgcacaaactttcaacctggatacctacttatcccaaagacaacaa 1140 caagttgaagaggccctaagtgctgctcttgtgccagcttatcctgagagaatatacgaa 1200 gctatgagatactccctcctggcaggtggcaaaagattaagacctatcttatgtttagct 1260 gcttgcgaattggcaggtggttctgttgaacaagccatgccaactgcgtgtgcacttgaa 1320 atgatccatacaatgtcactaattcatgatgacctgccagccatggataacgatgatttc 1380 agaagaggaaagccaactaatcacaaggtgttcggggaagatatagccatcttagcgggt 1440 gatgcgcttttagcttacgcttttgaacatattgcttctcaaacaagaggagtaccacct 1500 caattggtgctacaagttattgctagaatcggacacgccgttgctgcaacaggcctcgtt 1560 ggaggccaagtcgtagaccttgaatctgaaggtaaagctatttccttagaaacattggag 1620 tatattcactcacataagactggagccttgctggaagcatcagttgtctcaggcggtatt 1680 ctcgcaggggcagatgaagagcttttggccagattgtctcattacgctagagatataggc 1740 ttggcttttcaaatcgtcgatgatatcctggatgttactgctacatctgaacagttgggg 1800 aaaaccgctggtaaagaccaggcagccgcaaaggcaacttatccaagtctattgggttta 1860 gaagcctctagacagaaagcggaagagttgattcaatctgctaaggaagccttaagacct 1920 tacggttcacaagcagagccactcctagcgctggcagacttcatcacacgtcgtcagcat 1980 taa 1983 SEQIDNO:221 MASEKEIRRERFLNVFPKLVEELNASLLAYGMPKEACDWYAHSLNYNTPGGKLNRGLSVV 60 DTYAILSNKTVEQLGQEEYEKVAILGWCIELLQAYFLVADDMMDKSITRRGQPCWYKVPE 120 VGEIAINDAFMLEAAIYKLLKSHFRNEKYYIDITELFHEVTFQTELGQLMDLITAPEDKV 180 DLSKFSLKKHSFIVTFKTAYYSFYLPVALAMYVAGITDEKDLKQARDVLIPLGEYFQIQD 240 DYLDCFGTPEQIGKIGTDIQDNKCSWVINKALELASAEQRKTLDENYGKKDSVAEAKCKK 300 IFNDLKIEQLYHEYEESIAKDLKAKISQVDESRGFKADVLTAFLNKVYKRSKGSSTGSST 360 STGMVAQTFNLDTYLSQRQQQVEEALSAALVPAYPERIYEAMRYSLLAGGKRLRPILCLA 420 ACELAGGSVEQAMPTACALEMIHTMSLIHDDLPAMDNDDFRRGKPTNHKVFGEDIAILAG 480 DALLAYAFEHIASQTRGVPPQLVLQVIARIGHAVAATGLVGGQVVDLESEGKAISLETLE 540 YIHSHKTGALLEASVVSGGILAGADEELLARLSHYARDIGLAFQIVDDILDVTATSEQLG 600 KTAGKDQAAAKATYPSLLGLEASRQKAEELIQSAKEALRPYGSQAEPLLALADFITRRQH 660 SEQIDNO:222 atgacagagagggagctccacgcggatgtgcgaaggttctatcaacacacttctcaaact 60 ctaaccggcctgcgaccttatcccaccgagcgagaagtccaagatgcagccgcggcgtgg 120 cagcaaaaggacaacatcgagaatgccatccgcgaagcggttcgaaagggcagcccagat 180 agcggcggcactacggacaccgtcatacccctcagtgccgccgagaaacgcgctctgatc 240 aacgagattgaccattcgttctctgagaacgggatgtggatggtcatcttcactgtcagt 300 ctgagtgcctttctccagggctttgtacagagtagtcagaacggtgcaaatctctttgct 360 gatcagtggcttaagtctcagaagcatactgtcaactcccagttcgcttatgccaacgca 420 gctgtttacttcagcgctgctgttataggatgtccactggctgcaccgatgagttcactg 480 tttggtcgccgtggtgtcattattgtcgcctcatttctcatctttgcggcatccgttggc 540 tcggcttgcattacactcaatgacaacgcatggctgtctcttaggagcatcagactaatc 600 ggcggtgtcggcatgggcttaaaggctactagcacccccatcctcgcagcggaaacggca 660 gttggctcgtggagaggctcttcagttctgttatggcagctatgggtctcttttggcatc 720 atgatgtcttttattgtcaatatttgcttgaaccagattgacgacaagaatctaaagctc 780 cggttgattctggcgtctccagcagtgtttgcgcttatgctgatgtatactgtcgccaaa 840 tgccctgagtcattccgctactacttgatgccaggttcgagaaagtatagccctgagaag 900 gcatatgcctcgttgctacgattgcgcaacaccaaggtcggtcacaacacttctacacat 960 cccttttggcttaccccttcgttccccttcacaacctgcaccgtcgaacaacatctgata 1020 caagcggtcacagctacaagcagtcagagacttgtacttgacgccgccccgaaacctcga 1080 accctagtagttggagctgtcagtcactacgtgcgacaatactggaagatcctgaaagtc 1140 catcgccttcggaatgcagctattacaacagggattgtggctttgtcgcagcaactttct 1200 ggaattaacctcatggcgttctacggtgggacaacacttgtaggtattagtccaggcaat 1260 cagccaacagaagatcaaatctccaaggccatgctgtacaacttgatctttggtctgtcg 1320 aacttcttattctgcttacccgccatccattccatagacgttctgggaagaaggagggtt 1380 ctactcttcacaatcccaggtatggccttaaccttgatggcagcggctataagcttcaat 1440 acggcaaatgaggatgtgagaaacggacttgtagccttctggatctactttcacacagta 1500 ttttatagcccgggaatggggccagtgccgttcgtgttagcttcggaaagctttcctttg 1560 gcctttcgtgacaccggcgcatcgcttgcaatatccatcaaccttctattcgctggcctc 1620 ctggcatggctgcaacccctactggtcactggtattagattcgggggaacacttggggtg 1680 tttgctggcttgaacgtcgttgcctttgctctcatctttctcctgatggaggaaaccagc 1740 ggcgtacctcttgagtctctaggatctgtcttcgaccagtcgaagaaggatctgatccac 1800 ttccaactcttcaagtttttaccatggttcggtcggttcattcttggtaggagtagtctt 1860 gccgaaagaccagaacgtactgtcgacttgagtccgagctcggtgacagctgcttcggtc 1920 actgatgatgacgatgaggaacgcatttggaatagcgatactgtttcaagtggggtgagg 1980 ctcgccgatatgttggggggaaacggaagaggctga 2016 SEQIDNO:223 atgtccttcattaaaaacttgttatttggaggtgttaaaacaagtgaggatccaaccggg 60 ctcacaggtaacggggcctcaaacacaaacgattctaataaaggtagtgaaccggtagta 120 gcgggtaatttctttcctaggacgctttccaaatttaacggccacgacgatgaaaaaata 180 tttattgctattaggggcaaagtatacgactgcacaagagggaggcagttttacggtcca 240 agcgggccatacactaactttgcaggccatgatgcgtcgcgtggtcttgcattgaactcc 300 ttcgatctggacgttattaaagattgggatcagcctatcgatcccttagatgatctgaca 360 aaagaacagattgacgcactggatgagtggcaagagcattttgagaataagtacccatgc 420 attggtactctgattccggagcctggcgtgaacgtatga 459 SEQIDNO:224 MSFIKNLLFGGVKTSEDPTGLTGNGASNTNDSNKGSEPVVAGNFFPRTLSKFNGHDDEKI 60 FIAIRGKVYDCTRGRQFYGPSGPYTNFAGHDASRGLALNSFDLDVIKDWDQPIDPLDDLT 120 KEQIDALDEWQEHFENKYPCIGTLIPEPGVNV 152 SEQIDNO:225 atgtcaagtccattagacgcggctggtctagctattgctacaacagagttgtgcagaaac 60 ttggcgactgggctgtacttcattatcagagagatcagagatgcttctaaagatgcagaa 120 attatgcaagatacattagcagcgttacataccagattggaccaagttagagctttattt 180 gacgccaacgttccacagagtccattggaaaaagattatagaaactccatagacagaaca 240 ttagagaatattcacagagatctgtctttattaactagtaaattgcatattgacgtcatc 300 ttagaagcgaaaggttcaaaaagattagaggcctggtacgtcttacagcgtaaatttcaa 360 tcagatgatatcaggaatatcaaacagagacttgcagggtccgaggaactgcttcagtct 420 catttcgaaatgttgtcaatatatatctcttacaggaccagagacgaggtaacagacttt 480 aaagctttcgtcagaccgattttagagaagctgttgtttcatgcaacgttgacagaggaa 540 agacaaagataccaagcagctgagtcaagatctattaaaagattacaacacgtcactaat 600 gccctaggcactggtaatacattccctggagaagaatcagatttcgaatatcatgacgca 660 tttaagacttggaaagacaagtctgaagctatgattatgtctatcgcagatccaccttgg 720 catcaagtgtcaaattctaactacgtcccatcaattcgtaatgaatctcgtgatggcgca 780 tcaatattgccaactgtacgtgattttagagaaaaaaacggcatgtatcccagcttgcgt 840 gttacacccaacttaagccacgttgaagagatcttagatgaatcattacatcaggatgtt 900 acagaagatttgattaattggtgtaaagagcagggattcccagtcaacgtctcaaacttt 960 aggtacgatttaatttgggaggcggcacctgtggcccttaaaggaacgtcacctatgcat 1020 caagccataaaaactaataatatggttgttttggaaaaaatgttgtccagagattgtaac 1080 atagaagtcaggctggaggacggttctcaagatccaaccccactactattagctggctct 1140 gaactaaatgcagttgctgttaagctgttattaaccaaaggtgccaaagcagatgctaca 1200 gatagaactggaaaaacaggtctacatttgtgccaatcccctaaattcgagggtagaaga 1260 gtggctaaactattgttgggtgactctagagctgaggcgttagatgttaatgcacaagat 1320 cagtttggcatgactgcagctcacatcgccgctagagtaggcgatgttaaaatgttagag 1380 tacctactattggaccagtacggaaagaaggtagctgatgccaacgcccaacagcaagat 1440 ggttcaaccccgttgatggtcgcattgaaaagcaacatcgcaaataaaaaacaagtgatt 1500 gatgtcttgtctaggtgctccgatttgtcaattaaaaacaagaacggtgaagacgcgaaa 1560 gaggtagccgcaaagcatagtccgaaagatgtaagaaagtatcttttagctcatctagac 1620 caagattcaactaggtctcgtaggatctctgaatccacaacagttgtgtccggaatttct 1680 gtgcagatgagagaggaatcttgttcagggtgccgtaggcattgtccacaatttactgac 1740 tgtaaattgtcaataggtgactctgcattttcccaggattggaagagatccttgcgtaag 1800 tactcctctgatcaatcaagtatagcgatggggtctagcagttccattcgtcaggccaga 1860 taa 1863 SEQIDNO:226 attttgccaagttcgacatgctagaagaagaggctagagcacttgttagaaaagtaggc 60 aatgctgttgatcccatttacggattcagtacaacctcctgccaaatttacgatacggca 120 tgggctgctatgattagtaaggaagaacatggagataaggtttggttgtttccagaatct 180 ttcaaatacttactagaaaagcaaggtgaggatggtagttgggaaaggcatccaaggagt 240 aaaacagtaggggtgctaaatacagctgcagcgtgcttagctttattgcgtcacgttaag 300 aatccacttcagcttcaagatatagcagctcaggatatagaacttagaattcaaagaggt 360 ctaaggagtctagaagaacagcttattgcgtgggacgatgtccttgacacaaatcacatt 420 ggtgtcgagatgattgtcccggctctacttgattaccttcaagctgaagatgaaaatgta 480 gattttgaattcgagtcacactctttgcttatgcagatgtataaggagaagatggcccgt 540 ttctcaccagaatccttatatcgtgcaaggcccagttctgctctgcataatttagaagcg 600 ctaattggtaagcttgattttgataaggtgggtcaccatctgtacaatggtagtatgatg 660 gcctcaccttcatctactgcggctttcctaatgcatgcctcaccttggtcacacgaggca 720 gaagcatatctaagacatgtttttgaagctggcactgggaagggctccggcggatttccc 780 ggtacatatcctactacatactttgaattaaattgggttctatcaaccttgatgaaatca 840 gggtttactttgtcagatcttgagtgcgatgaattatcaagcatagcaaacactatagca 900 gagggtttcgaatgcgaccatggagtgatcgggtttgccccaagagctgttgatgttgat 960 gatactgcaaaaggactacttacccttacgttattgggcatggacgaaggggtgagccca 1020 gcacccatgattgcgatgtttgaagctaaagatcatttcctaacgttcctgggtgaaaga 1080 gatccttcattcaccagtaattgtcacgttctattatctttactacaccgtaccgactta 1140 ctgcaatatctgccacagattagaaaaactacaacttttctatgcgaagcctggtgggct 1200 tgtgatggtcaaataaaagataaatggcatcttagtcatctatatccgactatgttgatg 1260 gtccaggcatttgctgagatccttctgaagtccgcagaaggtgaaccattgcacgatgct 1320 ttcgacgcagccactttgtctagagtctcaatttgtgtttttcaagcttgtcttcgtact 1380 ttgttggcacaatcacaagatggtagctggcacggtcaaccggaggcgtcttgctatgca 1440 gtattaacactagctgagagcgggagacttgttcttttgcaagcgcttcaaccacagatt 1500 gcagccgccatggagaaggctgcggatgttatgcaagcgggaagatggtcctgtagcgat 1560 cacgattgtgattggacttccaaaacagcctaccgtgtagatttggtggctgcagcttac 1620 aggctggcagccatgaaggcttcctctaacttgacctttactgttgatgacaatgtgtca 1680 aagaggtccaacggttttcaacagttggtgggaagaacagatctattctctggagtgcca 1740 gcatgggaactgcaagcatcattcttagaaagtgcgctttttgttcccctattaaggaac 1800 catagactagatgtgtttgatagggacgacataaaagtttcaaaggatcattatttagat 1860 atgattccatttacgtgggtaggttgtaataacaggtctagaacatacgtgagtacgtcc 1920 ttcttattcgatatgatgatcatctctatgttaggttatcaaatagacgagttcttcgag 1980 gccgaagctgcacctgctttcgcacaatgtataggccaattacaccaagtcgttgacaaa 2040 gtcgttgatgaagtcatcgacgaagttgtcgacaaggtggtcggcaaggttgtgggcaag 2100 gttgtaggtaaggtggtggacgagcgtgtcgactctccgacccatgaagcaatagcgata 2160 tgcaatattgaagcctctttgaggagatttgtggatcatgttctacatcaccaacatgta 2220 ttacacgcaagccaacaagagcaagacattttatggcgtgaattgagagcttttttacac 2280 gctcacgttgtgcaaatggctgacaattctactctggcgcctcctggcaggacattcttc 2340 gactgggttaggacaactgctgctgatcatgtagcctgcgcttactctttcgcattcgcc 2400 tgctgtattacttccgcaacgatcggacagggccaatctatgttcgctactgttaatgag 2460 ctgtatcttgttcaagcagcagctagacatatgactaccatgtgcagaatgtgcaatgat 2520 attggtagtgttgatagggatttcattgaagccaatataaattctgttcatttccctgaa 2580 ttttctactctaagccttgtggcagataagaaaaaagcccttgcccgtttagcagcttat 2640 gaaaaatcttgtttgacccataccttagatcaatttgaaaatgaagttctacaatcccca 2700 agagtttcatccgcagcctccggcgattttaggacaaggaaagtggcagtggtaaggttc 2760 ttcgcggatgtgaccgatttttatgaccagttatatattctgagagatctttcatcttct 2820 ttaaagcatgtcggcacctaa 2841 SEQIDNO:227: MFAKFDMLEEEARALVRKVGNAVDPIYGFSTTSCQIYDTAWAAMISKEEHGDKVWLFPES 60 FKYLLEKQGEDGSWERHPRSKTVGVLNTAAACLALLRHVKNPLQLQDIAAQDIELRIQRG 120 LRSLEEQLIAWDDVLDTNHIGVEMIVPALLDYLQAEDENVDFEFESHSLLMQMYKEKMAR 180 FSPESLYRARPSSALHNLEALIGKLDFDKVGHHLYNGSMMASPSSTAAFLMHASPWSHEA 240 EAYLRHVFEAGTGKGSGGFPGTYPTTYFELNWVLSTLMKSGFTLSDLECDELSSIANTIA 300 EGFECDHGVIGFAPRAVDVDDTAKGLLTLTLLGMDEGVSPAPMIAMFEAKDHFLTFLGER 360 DPSFTSNCHVLLSLLHRTDLLQYLPQIRKTTTFLCEAWWACDGQIKDKWHLSHLYPTMLM 420 VQAFAEILLKSAEGEPLHDAFDAATLSRVSICVFQACLRTLLAQSQDGSWHGQPEASCYA 480 VLTLAESGRLVLLQALQPQIAAAMEKAADVMQAGRWSCSDHDCDWTSKTAYRVDLVAAAY 540 RLAAMKASSNLTFTVDDNVSKRSNGFQQLVGRTDLFSGVPAWELQASFLESALFVPLLRN 600 HRLDVFDRDDIKVSKDHYLDMIPFTWVGCNNRSRTYVSTSFLFDMMIISMLGYQIDEFFE 660 AEAAPAFAQCIGQLHQVVDKVVDEVIDEVVDKVVGKVVGKVVGKVVDERVDSPTHEAIAI 720 CNIEASLRRFVDHVLHHQHVLHASQQEQDILWRELRAFLHAHVVQMADNSTLAPPGRTFF 780 DWVRTTAADHVACAYSFAFACCITSATIGQGQSMFATVNELYLVQAAARHMTTMCRMCND 840 IGSVDRDFIEANINSVHFPEFSTLSLVADKKKALARLAAYEKSCLTHTLDQFENEVLQSP 900 RVSSAASGDFRTRKVAVVRFFADVTDFYDQLYILRDLSSSLKHVGT 946 SEQIDNO:228: atgcctggtaagatagaaaatggcaccccgaaagatttaaaaactggtaatgattttgtg 60 tctgccgcaaaatcattgcttgacagggcttttaaaagccatcacagttattacggttta 120 tgctccaccagctgtcaggtttacgatactgcgtgggtggcgatgattccaaaaacaaga 180 gacaatgtgaagcaatggctatttccggagtgtttccattacttgctgaaaacccaagct 240 gctgatggcagctggggttctttgccaactacacaaactgcaggtattctggatactgca 300 tctgctgtacttgccctgttatgccacgctcaggaaccattacaaatcttagatgtttca 360 ccagacgagatgggtttgcgtattgaacatggggtgacttctcttaagagacaattggct 420 gtttggaacgatgtcgaggacacaaatcacataggtgtagaattcattatcccagcttta 480 cttagcatgttggaaaaggaattggatgttccctcattcgaatttccttgtcgttcaatt 540 ctggaaagaatgcacggggaaaaacttgggcacttcgatcttgaacaagtctacggtaaa 600 ccgtcatccttgttacactctctagaggcttttttaggtaaattggacttcgataggttg 660 tctcatcacctataccacggttccatgatggctagcccgtcatctacggctgcttacttg 720 attggtgccacaaaatgggatgatgaggcagaagattatcttcgtcatgttatgaggaac 780 ggcgccggtcacggcaacggtggtatatctggtacattcccgactacacacttcgagtgc 840 tcatggataatagcaactttactaaaagtaggttttacattaaaacagattgatggtgat 900 ggcttgagggggctatctactatcttacttgaagcattgagggatgagaatggggtgata 960 ggattcgctccaagaacagcagatgtagatgatacagctaaagcgttgttggctttgagc 1020 ttggttaatcaaccagtttcccctgacatcatgatcaaggttttcgaggggaaagatcac 1080 tttaccacttttggcagcgaaagggatccttctttaacatccaacttacatgttctttta 1140 tctttgttgaagcagtcaaatttgagtcagtaccatccccagatcttaaagaccacacta 1200 tttacatgtagatggtggtggggttccgatcactgcgtaaaagataagtggaacctttct 1260 catctatatcctacaatgttattagtcgaggcattcacggaagttcttcacttaattgac 1320 ggcggtgaactatccagcctatttgatgaatcctttaagtgcaaaataggtttatcaatc 1380 tttcaagcagtattgcgtatcatactaacacaagataatgatggtagctggcgtggatat 1440 agagaacaaacatgttacgctatcttggctttagttcaggctagacacgtctgtttcttc 1500 actcatatggtagacagattgcagagttgcgtggacagaggtttttcctggcttaaatcc 1560 tgttcatttcattctcaagatttaacgtggacttctaagacagcatatgaagttgggttc 1620 gtagctgaggcatataaattagctgcattgcagtcagcgtctcttgaagtgccggcagcc 1680 accatcggacatagtgttacgagtgcagtaccttcatctgatcttgaaaaatatatgagg 1740 ttagttagaaaaacggccttgttttccccgttggatgagtggggtcttatggcttccatt 1800 atagaatctagtttttttgtgccacttttacaagcccagagagttgagatttacccaaga 1860 gacaacattaaggttgatgaggacaagtacttgagcattatcccattcacctgggtcgga 1920 tgtaacaaccgttctagaactttcgcctctaacagatggttatatgatatgatgtatttg 1980 tcattgttgggttaccaaactgatgagtacatggaagcagttgccgggcccgtgttcgga 2040 gacgtgtctttattgcaccaaactatagacaaggtgatagataatactatgggtaatttg 2100 gctagagcaaacggtacggttcatagtggtaatggtcaccagcacgaatctccgaatata 2160 ggtcaggtcgaagacactctgacaagatttactaattccgttctaaatcataaagacgta 2220 ttaaacagttccagttcagatcaggatactttaagaagagaattccgtacattcatgcat 2280 gcacatattactcaaattgaggacaattctaggttttctaagcaagcttcctcagatgca 2340 ttctcatctccagaacagtcttatttccagtgggttaattccacaggaggctctcatgtt 2400 gcctgcgcctatagcttcgctttttcaaactgtctgatgagtgcgaatttactacagggc 2460 aaggatgcatttccttctggtactcagaaataccttatctcatcagttatgagacatgcg 2520 actaatatgtgcagaatgtacaatgattttgggagtatagccagagataatgctgaaaga 2580 aatgttaatagtatccattttcctgagtttacactgtgcaatggaacaagccagaaccta 2640 gacgaaagaaaagaaagattattgaaaatcgcaacttacgagcagggctacctagatagg 2700 gcattagaagcgttggaaagacagtcaagagatgacgcaggtgacagggcaggatccaag 2760 gatatgagaaaactaaagattgtaaaacttttttgcgacgttacagacctgtacgaccaa 2820 ttatacgttattaaagatttgtcttcttctatgaaatga 2859 SEQIDNO:229: MPGKIENGTPKDLKTGNDFVSAAKSLLDRAFKSHHSYYGLCSTSCQVYDTAWVAMIPKTR 60 DNVKQWLFPECFHYLLKTQAADGSWGSLPTTQTAGILDTASAVLALLCHAQEPLQILDVS 120 PDEMGLRIEHGVTSLKRQLAVWNDVEDTNHIGVEFIIPALLSMLEKELDVPSFEFPCRSI 180 LERMHGEKLGHFDLEQVYGKPSSLLHSLEAFLGKLDFDRLSHHLYHGSMMASPSSTAAYL 240 IGATKWDDEAEDYLRHVMRNGAGHGNGGISGTFPTTHFECSWIIATLLKVGFTLKQIDGD 300 GLRGLSTILLEALRDENGVIGFAPRTADVDDTAKALLALSLVNQPVSPDIMIKVFEGKDH 360 FTTFGSERDPSLTSNLHVLLSLLKQSNLSQYHPQILKTTLFTCRWWWGSDHCVKDKWNLS 420 HLYPTMLLVEAFTEVLHLIDGGELSSLFDESFKCKIGLSIFQAVLRIILTQDNDGSWRGY 480 REQTCYAILALVQARHVCFFTHMVDRLQSCVDRGFSWLKSCSFHSQDLTWTSKTAYEVGF 540 VAEAYKLAALQSASLEVPAATIGHSVTSAVPSSDLEKYMRLVRKTALFSPLDEWGLMASI 600 IESSFFVPLLQAQRVEIYPRDNIKVDEDKYLSIIPFTWVGCNNRSRTFASNRWLYDMMYL 660 SLLGYQTDEYMEAVAGPVFGDVSLLHQTIDKVIDNTMGNLARANGTVHSGNGHQHESPNI 720 GQVEDTLTRFTNSVLNHKDVLNSSSSDQDTLRREFRTFMHAHITQIEDNSRFSKQASSDA 780 FSSPEQSYFQWVNSTGGSHVACAYSFAFSNCLMSANLLQGKDAFPSGTQKYLISSVMRHA 840 TNMCRMYNDFGSIARDNAERNVNSIHFPEFTLCNGTSQNLDERKERLLKIATYEQGYLDR 900 ALEALERQSRDDAGDRAGSKDMRKLKIVKLFCDVTDLYDQLYVIKDLSSSMK 952 SEQIDNO:230: atgagtaagtctaatagtatgaattctacatcacacgaaaccctttttcaacaattggtc 60 ttgggtttggaccgtatgccattgatggatgttcactggttgatctacgttgctttcggc 120 gcatggttatgttcttatgtgatacatgttttatcatcttcctctacagtaaaagtgcca 180 gttgttggatacaggtctgtattcgaacctacatggttgcttagacttagattcgtctgg 240 gaaggtggctctatcataggtcaagggtacaataagtttaaagactctattttccaagtt 300 aggaaattgggaactgatattgtcattataccacctaactatattgatgaagtgagaaaa 360 ttgtcacaggacaagactagatcagttgaacctttcattaatgattttgcaggtcaatac 420 acaagaggcatggttttcttgcaatctgacttacaaaaccgtgttatacaacaaagacta 480 actccaaaattggtttccttgaccaaggtcatgaaggaagagttggattatgctttaaca 540 aaagagatgcctgatatgaaaaatgacgaatgggtagaagtagatatcagtagtataatg 600 gtgagattgatttccaggatctccgccagagtctttctagggcctgaacactgtcgtaac 660 caggaatggttgactactacagcagaatattcagaatcacttttcattacagggtttatc 720 ttaagagttgtacctcatatcttaagaccattcatcgcccctctattaccttcatacagg 780 actctacttagaaacgtttcaagtggtagaagagtcatcggtgacatcataagatctcag 840 caaggggatggtaacgaagatatactttcctggatgagagatgctgccacaggagaggaa 900 aagcaaatcgataacattgctcagagaatgttaattctttctttagcatcaatccacact 960 actgcgatgaccatgacacatgccatgtacgatctatgtgcttgccctgagtacattgaa 1020 ccattaagagatgaagttaaatctgttgttggggcttctggctgggacaagacagcgtta 1080 aacagatttcataagttggactccttcctaaaagagtcacaaagattcaacccagtattc 1140 ttattgacattcaatagaatctaccatcaatctatgaccttatcagatggcactaacatt 1200 ccatctggaacacgtattgctgttccatcacacgcaatgttgcaagattctgcacatgtc 1260 ccaggtccaaccccacctactgaatttgatggattcagatatagtaagatacgttctgat 1320 agtaactacgcacaaaagtacctattctccatgaccgattcttcaaacatggctttcgga 1380 tacggcaagtatgcttgtccaggtagattttacgcgtctaatgagatgaaactaacatta 1440 gccattttgttgctacaatttgagttcaaactaccagatggtaaaggtcgtcctagaaat 1500 atcactatcgattctgatatgattccagacccaagagctagactttgcgtcagaaaaaga 1560 tcacttagagatgaatga 1578 SEQIDNO:231 MSKSNSMNSTSHETLFQQLVLGLDRMPLMDVHWLIYVAFGAWLCSYVIHVLSSSSTVKVP 60 VVGYRSVFEPTWLLRLRFVWEGGSIIGQGYNKFKDSIFQVRKLGTDIVIIPPNYIDEVRK 120 LSQDKTRSVEPFINDFAGQYTRGMVFLQSDLQNRVIQQRLTPKLVSLTKVMKEELDYALT 180 KEMPDMKNDEWVEVDISSIMVRLISRISARVFLGPEHCRNQEWLTTTAEYSESLFITGFI 240 LRVVPHILRPFIAPLLPSYRTLLRNVSSGRRVIGDIIRSQQGDGNEDILSWMRDAATGEE 300 KQIDNIAQRMLILSLASIHTTAMTMTHAMYDLCACPEYIEPLRDEVKSVVGASGWDKTAL 360 NRFHKLDSFLKESQRFNPVFLLTFNRIYHQSMILSDGINIPSGTRIAVPSHAMLQDSAHV 420 PGPTPPTEFDGFRYSKIRSDSNYAQKYLFSMTDSSNMAFGYGKYACPGRFYASNEMKLTL 480 AILLLQFEFKLPDGKGRPRNITIDSDMIPDPRARLCVRKRSLRDE 525 SEQIDNO:232 atgtctattttcaacatgattacttcatatgctgggagtcaactcttaccattttacata 60 gcaatattcgttttcacattggttccatgggctattagattctcatggttggaacttaga 120 aaggggtcagtagtgccactggccaacccacctgactcattattcggcacaggcaagaca 180 cgtagatctttcgttaaactttccagagaaatactagccaaggcaagatctctatttcca 240 aacgaaccatttagattgatcacagactggggagaggttcttattcttcctcctgatttt 300 gccgatgaaattagaaacgatcctagattatctttctctaaagctgcaatgcaggataat 360 catgccggcatcccaggtttcgaaacagtcgcattagttggtagagaagatcaacttatt 420 caaaaagttgctagaaaacaactcacaaagcacctgtctgcagtcatagagcctttatct 480 agagagtcaaccctagccgtttcattgaattttggtgaaactactgaatggagagctata 540 agactaaagccagccattttggatatcattgctagaatcagctccagaatctacctaggg 600 gatcagttgtgcagaaatgaggcatggttgaagattacaaagacatatacaaccaacttc 660 tacactgcttctacaaacttgcgtatgttcccaagatcaatcagaccattagcgcactgg 720 ttcttgcctgaatgcagaaagttgagacaagagagaaaagatgctataggtatcattaca 780 ccattgatcgaaagacgtagagagttacgtagagcagcaatcgctgccggtcaacctctc 840 ccagtgtttcatgatgcaatcgactggtctgaacaggaagctgaggcagccggaactggt 900 gccagtttcgaccctgttatctttcaactaaccttgtccttgctggcaattcataccact 960 tacgatctgttacaacaaactatgattgatttaggtagacacccagagtacattgaacca 1020 ctaagacaagaggtagtacagctgttgagagaagagggatggaaaaagaccacattattc 1080 aagatgaagttattagactccgcgattaaggaaagtcagagaatgaaacctggttctata 1140 gtcacaatgcgtagatacgttactgaggatatcaccctttcatcaggtcttacattgaaa 1200 aagggaacaagattgaacgtggacaatagaagattggatgatcctaagatttacgataac 1260 ccagaagtctacaatccatacagattttacgatatgagatccgaagcgggtaaggaccat 1320 ggtgctcaattagtatctacaggttcaaaccacatgggttttggtcatggacaacattct 1380 tgtccaggcagattcttcgctgcaaacgaaatcaaggttgcactatgtcatatcttagtg 1440 aaatacgactggaagctctgtccagatactgaaactaagccagacacaagaggcatgatt 1500 gctaagagttctccagttactgatatccttatcaaaagacgtgaaagcgtcgaacttgat 1560 ttggaagcaatttag 1575 SEQIDNO:233 MSIFNMITSYAGSQLLPFYIAIFVFTLVPWAIRFSWLELRKGSVVPLANPPDSLFGTGKT 60 RRSFVKLSREILAKARSLFPNEPFRLITDWGEVLILPPDFADEIRNDPRLSFSKAAMQDN 120 HAGIPGFETVALVGREDQLIQKVARKQLTKHLSAVIEPLSRESTLAVSLNFGETTEWRAI 180 RLKPAILDIIARISSRIYLGDQLCRNEAWLKITKTYTINFYTASTNLRMFPRSIRPLAHW 240 FLPECRKLRQERKDAIGIITPLIERRRELRRAAIAAGQPLPVFHDAIDWSEQEAEAAGTG 300 ASFDPVIFQLTLSLLAIHTTYDLLQQTMIDLGRHPEYIEPLRQEVVQLLREEGWKKTTLF 360 KMKLLDSAIKESQRMKPGSIVIMRRYVTEDITLSSGLTLKKGTRLNVDNRRLDDPKIYDN 420 PEVYNPYRFYDMRSEAGKDHGAQLVSTGSNHMGFGHGQHSCPGRFFAANEIKVALCHILV 480 KYDWKLCPDTETKPDTRGMIAKSSPVTDILIKRRESVELDLEAI 524 SEQIDNO:234 atgagcatcttcaatatgatcaccagctatgcgggtagccaacttttgcccttctacatc 60 gccatattcgtctttactttagtcccatgggcaatccgcttctcttggctagaattgcgc 120 aagggctcagtggtgccacttgcgaacccgcccgactcactgttcggcaccggtaaaacc 180 aggaggagttttgtcaagcttagtagagaaattctcgctaaagcgaggagcttgttccct 240 aatgagccatttcgcttgattacggactggggtgaggttctcattctccccccagacttt 300 gcagatgagattagaaatgatccgagactgagcttctccaaggcggcgatgcaggataat 360 catgctggaatacctggctttgagactgttgccctggtgggtcgtgaagaccaacttatt 420 cagaaggtggcccgaaagcagttgaccaagcatctttccgctgtcatagagccactatct 480 agagagtccaccctcgcagtgtcgctcaactttggagagacaacagaatggcgagcgata 540 cgcctcaagcccgcaattctagacatcatcgcccgcatctcgtccagaatctatctcggc 600 gaccaactatgccgcaacgaagcttggctgaagatcacaaagacatacaccaccaacttc 660 tacactgcatctaccaacctccgaatgtttcctcgatcgatccgtcctctcgcccactgg 720 ttcctccccgaatgcagaaagcttcgacaggagcgcaaggatgcaatcggtattattacg 780 ccactgattgagcgccgccgtgagcttcgaagagctgcgatcgcagctggtcagcctctg 840 cctgtgttccacgacgctattgactggtcggaacaggaggcagaagctgcaggcacaggg 900 gcctcgtttgaccccgtgatcttccagcttacgctctctcttctggcaattcatacgacg 960 tatgatctcctccagcaaacgatgattgaccttggtcgccacccagagtatatcgagcct 1020 cttagacaggaagttgttcaacttcttcgtgaagaaggttggaagaaaacaacgcttttc 1080 aagatgaagctccttgacagtgctatcaaagagtctcagcgaatgaagcctggaagcata 1140 gttaccatgcgtcgctacgtaaccgaagacatcaccctctctagcggcctgaccctcaaa 1200 aaagggacccgcctcaacgttgacaacagacgcctcgacgatcccaaaatctacgataac 1260 cccgaggtttacaatccttatcgcttctacgacatgcgctccgaagccgggaaagaccat 1320 ggggcacagctagtatcaactggctcaaaccatatgggcttcggccacggtcagcactca 1380 tgcccagggcgtttcttcgctgcgaatgagatcaaagtagcgctatgccacatcttggtc 1440 aagtatgattggaagctgtgccctgacacggagaccaagcctgataccaggggcatgatt 1500 gccaagtccagccctgtcacggacatcttgatcaagcgtcgggagtcagttgagttggat 1560 ttggaagcaatttga 1575 SEQIDNO:235 MSIFNMITSYAGSQLLPFYIAIFVFTLVPWAIRFSWLELRKGSVVPLANPPDSLFGTGKT 60 RRSFVKLSREILAKARSLFPNEPFRLITDWGEVLILPPDFADEIRNDPRLSFSKAAMQDN 120 HAGIPGFETVALVGREDQLIQKVARKQLTKHLSAVIEPLSRESTLAVSLNFGETTEWRAI 180 RLKPAILDIIARISSRIYLGDQLCRNEAWLKITKTYTINFYTASTNLRMFPRSIRPLAHW 240 FLPECRKLRQERKDAIGIITPLIERRRELRRAAIAAGQPLPVFHDAIDWSEQEAEAAGTG 300 ASFDPVIFQLTLSLLAIHTTYDLLQQTMIDLGRHPEYIEPLRQEVVQLLREEGWKKTTLF 360 KMKLLDSAIKESQRMKPGSIVIMRRYVTEDITLSSGLTLKKGTRLNVDNRRLDDPKIYDN 420 PEVYNPYRFYDMRSEAGKDHGAQLVSTGSNHMGFGHGQHSCPGRFFAANEIKVALCHILV 480 KYDWKLCPDTETKPDTRGMIAKSSPVTDILIKRRESVELDLEAI 524 SEQIDNO:236 atgaaacacattgatgtgatgaacttcatatcgaaaatatgctcctggtctaaggacagc 60 ccaggattcgtccttctgatttcaattctggtgatactcggcagtgtcaccttcattccc 120 aagtgtggcagaagaagcgcctttgatgctttgcccattgtgaacaaaccaaagtttggt 180 cccattttctcaatcattgctcgatggagatttattcaccaaagcaagaagatattggaa 240 gagggacagaagtgctacagcaaccgcccctttcgcatatggacagactggggcgaagta 300 ctcatgttgacaccggattatgcgcacgaaatacgcaatgacccgcatctcagcttttct 360 ggagctgtgaaaatcgacggccacgcggatataccgggcttcgagactgtgaaactgatt 420 tcgcatccagacaacctgattcagctagtagcaaggaagcaattaaccagacaccttgcg 480 gctgtgattcagcctctttctagtgttacagaggaagccctcatcaagaatttagggaaa 540 tcacaagaatggtctgagatttatctaaaatatgctgttctagatatcattgcccgacta 600 tcctcgcgcatttacttcggagaactactgtaccagaacgaagaatggctttccattgta 660 aaaaattatgccactcacttcttcactgccagctccgatctacgcaaagttccttgggcc 720 tttcgctcactagtccattggttcgtgccgtcctgccgagcgctaaggcttgagcgctac 780 aatgcgcgtcgtgtcttagaaccggttatcagccagcgtcgtcaactgaaggaagctgcc 840 aaaacggctggaggtacaccgttacacttcgaggatgccattgaatgggccgaagtagaa 900 gctcgagtgaaaggaacaaaatatgatccagtaattttccaattgacgctctcgcttctg 960 gcaatacacacaacatacgatctcctcgagatgtgtatgattgatctcgcaaagcgcccc 1020 gactgtatcgaggaccttcgtaaagaagtcattacagtactccgcaaggatggctggacg 1080 aagaatgctctgtacaacatgaagctgctcgactctgcaataaaagagtctcaacgcctc 1140 aaaccaggaagtatcacatcaatgcgtcgctacgctacttcagacgtacaactgcgcgac 1200 ggcgtagttctcaaaaagggcaataggctgaatgttcttaccttgcaccgatccccagac 1260 ctattcccttcaccggatacctacgacccatatcggttctacaacatacgcggacagcct 1320 gggaaagagaactgggcgcaactagtatcgacatctgttgaacatatgggctttggtcat 1380 ggggaacactcgtgccctggacgattctttgcggcaaacgaaattaaggtagcacttgcg 1440 catatcctcgtcaagtacgactggaagctgtcagacgaggcgggcggttgtactgaggtc 1500 aagggcatggtcgaaaaggcaggaagtaaggtcaagatactggtgagacaaaggcaagac 1560 gtggagagcgtccttgatgaggcgtga 1587 SEQIDNO:237 MKHIDVMNFISKICSWSKDSPGFVLLISILVILGSVTFIPKCGRRSAFDALPIVNKPKFG 60 PIFSIIARWRFIHQSKKILEEGQKCYSNRPFRIWTDWGEVLMLTPDYAHEIRNDPHLSFS 120 GAVKIDGHADIPGFETVKLISHPDNLIQLVARKQLTRHLAAVIQPLSSVTEEALIKNLGK 180 SQEWSEIYLKYAVLDIIARLSSRIYFGELLYQNEEWLSIVKNYATHFFTASSDLRKVPWA 240 FRSLVHWFVPSCRALRLERYNARRVLEPVISQRRQLKEAAKTAGGTPLHFEDAIEWAEVE 300 ARVKGTKYDPVIFQLTLSLLAIHTTYDLLEMCMIDLAKRPDCIEDLRKEVITVLRKDGWT 360 KNALYNMKLLDSAIKESQRLKPGSITSMRRYATSDVQLRDGVVLKKGNRLNVLTLHRSPD 420 LFPSPDTYDPYRFYNIRGQPGKENWAQLVSTSVEHMGFGHGEHSCPGRFFAANEIKVALA 480 HILVKYDWKLSDEAGGCTEVKGMVEKAGSKVKILVRQRQDVESVLDEA 528 SEQIDNO:238 ATGAGCGAAACATACACGACAGCAGAAGTTGGAAAGCATAAGGACGAGGCGAATGGCTTC 60 TGGTTGATAGTTGAGAATGACGTTTACGACGTCACGAAGTTTATTGACGAGCACCCTGGC 120 GGTGCCAAGATTCTAAAAAGGTGGTCTGGAAAAAACGCAACTAAGGCATTCTGGAAGTAT 180 CATAATGAACACGTACTTGCTAAATACGGTAAGGACCTTAAAATAGGCGCCGTTGGCGAG 240 AGCGCGAAACTATGA SEQIDNO:239 MSETYTTAEVGKHKDEANGFWLIVENDVYDVTKFIDEHPGGAKILKRWSGKNATKAFWKY 60 HNEHVLAKYGKDLKIGAVGESAKL SEQIDNO:240 ATGTTTGCTAGGAGTGCTTTCAGAGCAGCACAACCCCTTAGAAGCGTTAGGAGGTATGCCACAGAAGCGGGTGGAGCGGGTGGTAGCA ACGCTTTCCTGTACGCTGCGGGCGCAGCCGCCTTTGGAGGAGCAGGCTATTGGTATTTCAGCAAGGGTGGTGCTCCGAGCGCTGCGGC TGCGGCGGCCGATGTGAAACAGGCCGTTGGTATCGAACCGAAAAAAGCATTCACGGGAGGCGATCAAGGTTTCGTTAGCTTGAAACTT TCCGATGTGGAGTTGGTAAACCACAATACAAAACGTCTTAGATTCGAGCTACCCGAGCCCGACCAAGTTAGTGGATTGCATGTGGCTT CAGCGATTTTGACGAAGTACAAAGGGCCGAATGACGAGAAGGCAACACTAAGGCCATATACGCCCATTTCTGACGAATCCGAAAAAGG TTTTATAGACCTACTTGTAAAGAAGTACCCCGATGGCCCCATGAGTACGCACTTACACAATCTGGTACCAGGCCAACGTCTAGATATA AAGGGTCCGCTTCCCAAGTACCCGTGGGAGGAGAATAAGCACGAACATATTGCGCTAATAGCGGGTGGTACCGGGATTACACCAATGT ATCAGTTGGCGAGGGCGATATTTAACAATCCAAACGACAAGACAAAGGTGACACTGGTGTTTGGTAATGTTTCCGAACAGGACATTCT GCTAAAAAAGGAGTTCGAGCACCTAGAAAACACGTTCCCTCAGAGGTTCCGTGCATTCTACGTTCTTGATAATCCGCCTAAGGAATGG GTTGGTAACTCTGGTTATATAAGCAAAGAGCTACTGAAAACAGTTTTGCCTGAGCCTAAGAACGAGAATATTAAACTGTTCGTGTGCG GCCCCCCGGGCTTAATGAACGCTATCTCAGGAAACAAGGTATCACCAAAAAACCAAGGAGAACTAACCGGCGCACTAAAGGAGCTAGG GTATAAGGAGGATCAGGTCTATAAATTTTAA SEQIDNO:241 MFARSAFRAAQPLRSVRRYATEAGGAGGSNAFLYAAGAAAFGGAGYWYFSKGGAPSAAAAAADVKQAVGIEPKKAFTGGDQGFVSLKL SDVELVNHNTKRLRFELPEPDQVSGLHVASAILTKYKGPNDEKATLRPYTPISDESEKGFIDLLVKKYPDGPMSTHLHNLVEGQRLDI KGPLPKYPWEENKHEHIALIAGGYGITPMYQLARAIFNNPNDKTKVTLVFGNVSEQDILLKKEFEHLENTFPQRFRAFYVLDNPPKEW VGNSGYISKELLKTVLPEPKNENIKLFVCGPPGLMNAISGNKVSPKNQGELTGALKELGYKEDQVYKF