BIOSYNTHETIC METHODS FOR THE MODIFICATION OF CANNABINOIDS
20220298533 · 2022-09-22
Assignee
Inventors
Cpc classification
C12P17/06
CHEMISTRY; METALLURGY
C12Y121/03007
CHEMISTRY; METALLURGY
C12Y106/02004
CHEMISTRY; METALLURGY
International classification
Abstract
Provided is a method of modifying a first cannabinoid into a second cannabinoid or a non-cannabinoid. The method comprises combining the first cannabinoid with an enzyme that can modify the first cannabinoid into the second cannabinoid or non-cannabinoid under conditions where the first cannabinoid is modified into the second cannabinoid or non-cannabinoid. Also provided is a non-naturally occurring enzyme that can modify a first cannabinoid into a second cannabinoid or a non-cannabinoid. A nucleic acid encoding that enzyme is additionally provided. Further provided is a non-naturally occurring nucleic acid that encodes an enzyme having the enzymatic activity of the above non-naturally occurring enzyme. An expression cassette comprising that nucleic acid is additionally provided. A cell comprising the above expression cassette is further provided. Also provided is a plant expression cassette comprising the above-identified nucleic acid.
Claims
1-76. (canceled)
77. A nucleic acid encoding an enzyme that can modify a first cannabinoid into a second cannabinoid or a non-cannabinoid, wherein the nucleic acid comprises any one of SEQ ID NOs:1-50.
78-88. (canceled)
89. An expression cassette comprising the nucleic acid of claim 77.
90-91. (canceled)
92. A cell comprising the expression cassette of claim 89, capable of expressing the enzyme that can modify a first cannabinoid into a second cannabinoid or a non-cannabinoid.
93. The cell of claim 92, which is a bacterial cell.
94. The cell of claim 92, which is a yeast cell.
95. The yeast cell of claim 95, which is a species of Saccharomyces, Candida, Pichia, Schizosaccharomyces, Scheffersomyces, Blakeslea, Rhodotorula, or Yarrowia.
96. The cell of claim 92, further comprising a THC biosynthetic pathway that allows the yeast cell to produce the first cannabinoid.
97. The cell of claim 96, wherein the cell can synthesize the first cannabinoid from a non-cannabinoid.
98. The cell of claim 96, wherein the cell comprises a recombinant geranyl pyrophosphate synthase and a cannabinoid synthase, wherein the cannabinoid synthase can combine a polyprenyl pyrophosphate with alkylresorcylic acid to create a cannabinoid.
99. The cell of claim 92, wherein the first cannabinoid is THC or THCA and the second cannabinoid is CBN or CBNA.
100-105. (canceled)
106. The cell of claim 92, wherein the first and/or second cannabinoid comprises the structure ##STR00004## wherein R.sub.1═CH.sub.3, CH.sub.2CH.sub.3, (CH.sub.2).sub.2CH.sub.3, (CH.sub.2).sub.3CH.sub.3, (CH.sub.2).sub.3CH.sub.3, (CH.sub.2).sub.4CH.sub.3, (CH.sub.2).sub.5CH.sub.3, or (CH.sub.2).sub.6CH.sub.3; R.sub.2═H or COOH; and R.sub.3═CH.sub.3 or CH.sub.2OH.
107. The cell of claim 92, wherein the enzyme is an aromatase, a dehydrogenase, an oxidase or a desaturase.
108. The cell of claim 92, wherein the enzyme is an oxidase.
109. The cell of claim 108, wherein the oxidase is a laccase comprising an amino acid sequence comprising any one of SEQ ID NOs:92-100.
110. The cell of claim 108, wherein the oxidase is a cytochrome P450, expressed with a cytochrome P450 reductase (CPR).
111. The cell of claim 108, wherein the oxidase is selected from the group consisting of a flavin-dependent monooxygenase, a copper-dependent monooxygenase, a multicopper oxidase, a bacterial polysaccharide monooxygenase, a non-heme iron-dependent monooxygenase, a pterin-dependent monooxygenase, a diiron hydroxylase, an alpha-ketoglutarate-dependent hydroxylase, a cofactor-dependent monooxygenase, and a cofactor-independent monooxygenase.
112. The cell of claim 108, wherein the oxidase is a copper-dependent monooxygenase comprising an amino acid sequence having SEQ ID NO:89 or multicopper oxidase comprising an amino acid sequence having SEQ ID NO:90 or 91.
113. The cell of claim 92, wherein the first cannabinoid is converted into a second cannabinoid.
114. The cell of claim 113, wherein the first cannabinoid is tetrahydrocannabinol (THC) or tetrahydrocannabinolic acid (THCA) and the second cannabinoid is cannabinol (CBN) or cannabinolic acid (CBNA) and the enzyme is a desaturase, an aromatase, a dehydrogenase, or an oxidase.
115. The call of claim 113, wherein the first cannabinoid is tetrahydrocannabivarinic acid (THCVA), tetrahydrocannabiphorolic acid (TCHPA), tetrahydrocannabiorcinic acid (THCOA) or sesquiTHCA (THCFA) and the second cannabinoid is cannabinerolic acid (CBNA), cannabinerovarinic acid (CBNVA), cannabiphorolic acid (CBNPA), cannabinorcinic acid (CBNOA) or sesqui cannabinerolic acid (sesqui-CBNA), respectively.
Description
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
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DETAILED DESCRIPTION OF THE INVENTION
Abbreviations and Definitions
[0035] To facilitate understanding of the invention, a number of terms and abbreviations as used herein are defined below as follows:
[0036] Conservative amino acid substitutions: As used herein, when referring to mutations in a protein, “conservative amino acid substitutions” are those in which at least one amino acid of the polypeptide encoded by the nucleic acid sequence is substituted with another amino acid having similar characteristics. Examples of conservative amino acid substitutions are ser for ala, thr, or cys; lys for arg; gln for asn, his, or lys; his for asn; glu for asp or lys; asn for his or gln; asp for glu; pro for gly; leu for ile, phe, met, or val; val for ile or leu; ile for leu, met, or val; arg for lys; met for phe; tyr for phe or trp; thr for ser; trp for tyr; and phe for tyr.
[0037] Functional variant: The term “functional variant,” as used herein, refers to a recombinant enzyme such as a CBN synthase that comprises a nucleotide and/or amino acid sequence that is altered by one or more nucleotides and/or amino acids compared to the nucleotide and/or amino acid sequences of the parent protein and that is still capable of performing an enzymatic function (e.g., synthesis of CBN) of the parent enzyme. In other words, the modifications in the amino acid and/or nucleotide sequence of the parent enzyme may cause desirable changes in reaction parameters without altering fundamental enzymatic function encoded by the nucleotide sequence or containing the amino acid sequence. The functional variant may have conservative change including nucleotide and amino acid substitutions, additions and deletions. These modifications can be introduced by standard techniques known in the art, such as site-directed mutagenesis and random PCR-mediated mutagenesis, and may comprise natural as well as non-natural nucleotides and amino acids. Also envisioned is the use of amino acid analogs, e.g. amino acids not DNA or RNA encoded in biological systems, and labels such as fluorescent dyes, radioactive elements, electron dense agents, or any other protein modification, now known or later discovered.
[0038] Recombinant nucleic acid and recombinant protein: As used herein, a recombinant nucleic acid or protein is a nucleic acid or protein produced by recombinant DNA technology, e.g., as described in Green and Sambrook (2012).
[0039] Polypeptide, protein, and peptide: The terms “polypeptide,” “protein,” and “peptide” are used herein interchangeably to refer to amino acid chains in which the amino acid residues are linked by peptide bonds or modified peptide bonds. The amino acid chains can be of any length of greater than two amino acids. Unless otherwise specified, the terms “polypeptide,” “protein,” and “peptide” also encompass various modified forms thereof. Such modified forms may be naturally occurring modified forms or chemically modified forms. Examples of modified forms include, but are not limited to, glycosylated forms, phosphorylated forms, myristoylated forms, palmitoylated forms, ribosylated forms, acetylated forms, and the like. Modifications also include intra-molecular crosslinking and covalent attachment of various moieties such as lipids, flavin, biotin, polyethylene glycol or derivatives thereof, and the like. In addition, modifications may also include protein cyclization, branching of the amino acid chain, and cross-linking of the protein. Further, amino acids other than the conventional twenty amino acids encoded by genes may also be included in a polypeptide.
[0040] The term “protein” or “polypeptide” may also encompass a “purified” polypeptide that is substantially separated from other polypeptides in a cell or organism in which the polypeptide naturally occurs (e.g., 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, 100% free of contaminants).
[0041] Primer, probe and oligonucleotide: The terms “primer,” “probe,” and “oligonucleotide” may be used herein interchangeably to refer to a relatively short nucleic acid fragment or sequence. They can be DNA, RNA, or a hybrid thereof, or chemically modified analogs or derivatives thereof. Typically, they are single-stranded. However, they can also be double-stranded having two complementing strands that can be separated apart by denaturation. In certain aspects, they are of a length of from about 8 nucleotides to about 200 nucleotides. In other aspects, they are from about 12 nucleotides to about 100 nucleotides. In additional aspects, they are about 18 to about 50 nucleotides. They can be labeled with detectable markers or modified in any conventional manners for various molecular biological applications.
[0042] Vector: As used herein, the term “vector” refers to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. One type of vector is an episome, i.e., a nucleic acid capable of extra-chromosomal replication. Various vectors are those capable of autonomous replication and/expression of nucleic acids to which they are linked. Vectors capable of directing the expression of genes to which they are operatively linked are referred to herein as “expression vectors.”
[0043] Linker: The term “linker” refers to a short amino acid sequence that separates multiple domains of a polypeptide. In some embodiments, the linker prohibits energetically or structurally unfavorable interactions between the discrete domains.
[0044] Cannabinoid: As used herein, the term “cannabinoid” refers to a family of structurally related aromatic meroterpenoid molecules. Cannabinoids are generally formed by the enzymatic fusion, by a cannabinoid synthase (having geranylpyrophosphate:olivetolate geranyltransferase activity), of an alkylresorcylic acid
##STR00001##
where R.sup.1═CH.sub.3, (CH.sub.2).sub.2CH.sub.3 (divarinolic acid), (CH.sub.2).sub.4CH.sub.3 (olivetolic acid), or (CH.sub.2).sub.6CH.sub.3, with a polyprenyl pyrophosphate such as geranyl pyrophosphate, neryl pyrophosphate, geranylgeranyl pyrophosphate, of farnesyl pyrophosphate (
[0045] Codon optimized: As used herein, a recombinant gene is “codon optimized” when its nucleotide sequence is modified to accommodate codon bias of the host organism to improve gene expression and increase translational efficiency of the gene.
[0046] Expression cassette: As used herein, an “expression cassette” is a nucleic acid that comprises a gene and a regulatory sequence operatively coupled to the gene such that the promoter drives the expression of the gene in a cell. An example is a gene for an enzyme with a promoter functional in yeast, where the promoter is situated such that the promoter drives the expression of the enzyme in a yeast cell.
[0047] The present invention is directed to methods and compositions for modifying a first cannabinoid into a second cannabinoid or a non-cannabinoid using recombinant enzymes in microorganisms.
Methods of Modifying or Degrading Cannabinoids
[0048] In some embodiments, a method of modifying a first cannabinoid into a second cannabinoid or a non-cannabinoid is provided. The method comprises combining the first cannabinoid with an enzyme that can modify the first cannabinoid into the second cannabinoid or non-cannabinoid under conditions where the first cannabinoid is modified into the second cannabinoid or non-cannabinoid.
[0049] In these embodiments, the first cannabinoid and the second cannabinoid can be any cannabinoid now known or later discovered. In some of these embodiments, the first and/or second cannabinoid comprises the structure
##STR00002##
wherein R.sup.1═CH.sub.3, CH.sub.2CH.sub.3, (CH.sub.2).sub.2CH.sub.3, (CH.sub.2).sub.3CH.sub.3, (CH.sub.2).sub.3CH.sub.3, (CH.sub.2).sub.4CH.sub.3, (CH.sub.2).sub.5CH.sub.3, or (CH.sub.2).sub.6CH.sub.3; R.sub.2═H or COOH; and R.sub.3═CH.sub.3 or CH.sub.2OH.
[0050] Non-limiting examples of the first cannabinoid or the second cannabinoid are cannabigerolic acid (CBGA), cannabidiolic acid (CBDA), cannabichromene (CBC), cannabidivarin (CBCV), cannabichromenic acid (CBCA), cannabichromevarinic acid (CBCVA) cannabinol (CBN), cannabinerolic acid (CBNA), cannabivarin (CBV), cannabigerolic acid (CBGA), cannabinerovarinic acid (CBNVA), cannabigerophorolic acid (CBGPA), cannabigerovarinic acid (CBGVA), cannabigerogerovarinic acid (CB GGVA), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarin (THCV), tetrahydrocannabivarin acid (THCVA), cannabinerovarinic acid (CBNVA), sesquicannabigerol (CBF), cannabigerogerol (CBGG), sesqui-cannabigerolic acid (CBFA), cannabigerogerolic acid (CBGGA), sesquicannabigerolic acid (CBFA), sesquicannabidiolic acid (CBDFA), sesquiTHCA (THCFA), sesqui-cannabigerovarinic acid (CBFVA), sesquiCBCA (CBCFA), sesquiCBGPA (CBFPA), tetrahydrocannabivarin (THCV), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarinic acid (CBDVA), or cannabidivarin (CBDV) (
[0051] These methods can use any enzyme, now known or later discovered, that can carry out the conversion of the first cannabinoid into the second cannabinoid or degrade the first cannabinoid. In some embodiments, the enzyme is an aromatase, a dehydrogenase, an oxidase or a desaturase.
[0052] In some embodiments, the first cannabinoid is tetrahydrocannabinol (THC) or tetrahydrocannabinolic acid (THCA) and the second cannabinoid is cannabinol (CBN) or cannabinolic acid (CBNA). In other embodiments, the first cannabinoid is tetrahydrocannabivarinic acid (THCVA), tetrahydrocannabiphorolic acid (TCHPA), tetrahydrocannabiorcinic acid (THCOA) or sesquiTHCA (THCFA) and the second cannabinoid is cannabinerolic acid (CBNA), cannabinerovarinic acid (CBNVA), cannabiphorolic acid (CBNPA), cannabinorcinic acid (CBNOA) or sesqui cannabinerolic acid (sesqui-CBNA), respectively. In additional embodiments, the first cannabinoid is tetrahydrocannabivarinol (THCV), tetrahydrocannabiphorol (TCHP), tetrahydrocannabiorcinol (THCO) or sesquitetrahydrocannabinolic acid (sesquiTHCA) and the second cannabinoid is cannabinerovarinol (CBNV), cannabiphorol (CBNP), cannabinorcinol (CBNO) or sesqui cannabinerol (sesqui-CBN), respectively.
[0053] Exemplary enzymatic reactions are shown in
[0054] In various embodiments, the first cannabinoid is converted into a second cannabinoid that is an 11-hydroxy derivative of the first cannabinoid. In some of these embodiments, the conversion is carried out by the combination of a cytochrome P450 (CYP-450) and a cytochrome P450 reductase (CPR).
[0055] In various embodiments, a cannabinoid is oxidized by an oxidase into a polymeric state, such as a dimer of cannabinoids. This can occur between oxidized cannabinoids of the same species, such as THC or CBN, respectively, to form homopolymers, or a mixture of cannabinoid species, such as THC and CBN, which are oxidized to a heteropolymer of cannabinoids, as show in
[0056] The enzyme utilized in these methods can have any activity that can modify the first cannabinoid into the second cannabinoid. For example,
[0057] In some embodiments, the enzymes utilized in these methods additionally enable reduction of cannabinoid, e.g., THC, levels in pure cannabinoid preparations while not affecting other cannabinoid molecules. Cannabidiol (CBD) products often contain unwanted THC. Federal law bans any product containing more than 0.3% THC, so even small reductions in THC are critical to maintenance of cannabis products under this legal limit. Enzymes that destroy THC completely or convert THC to a molecule besides CBN are useful for certain applications and are commercially valuable.
[0058] The invention methods can be part of a complete biosynthesis pathway for cannabinoids such as CBN, including production of its acidic cannabinoid variant, cannabinolic acid (CBNA). The complete biosynthesis pathway for any cannabinoid is amenable to integration in a cannabinoid producing host cell. If the pathway includes a functional CBN synthase, accumulation of THC during an industrial fermentation is avoided.
[0059] The microorganism, e.g., yeast or bacterium, in which the methods are carried out can further comprise other enzymes, e.g., recombinantly transformed enzymes, that can affect the cannabinoid pathway, for example an enzyme that synthesizes the first cannabinoid from a non-cannabinoid or from another cannabinoid. This is illustrated in
[0060] To execute a CYP reaction, a CPR (cytochrome P450 reductase) is necessary to supply the P450 enzyme with reducing equivalents in the form of NADPH. The combination of the recombinant P450 and CPR genes and enzymes results in an 11-OH hydroxylase capable of acting on various cannabinoid substrates. In some embodiments, the hydroxyl group at the 11-position is added by recombinant CYP-450+CPR before the conversion of tetrahydrocannabinol or tetrahydrocannabinolic acid (THC/A) to CBN/A, yielding a conversion from 11-hydroxy tetrahydrocannabinol (11-OH THC) to 11-OH CBN.
[0061] The recombinant hydroxylation enzymes herein described may also hydroxylate other cannabinoid substrates, such as CBD, when expressed in a recombinant host capable of cannabinoid bioproduction. Additional reactions, substrates, and products for the above reconstituted biosynthetic pathways in a modified organism are depicted in
[0062] The enzymes used in these methods can be recombinantly expressed in a microorganism such as a yeast or bacterium, or a plant such as a Cannabis sp. In those systems, the gene for those enzymes can be modified, e.g., by codon optimizing the gene for the recombinant microorganism or plant.
[0063] In other embodiments, the enzyme is not naturally occurring. Such enzymes can be modified from a naturally occurring enzyme by, e.g., having conservative amino acid substitutions or substitutions that alter the enzymatic activity. Those enzymes can also be derived from a naturally occurring gene that has been codon optimized for expression in a recombinant host such as bacteria, yeast or plants.
[0064] In some of these methods, the first cannabinoid is converted (degraded) into a non-cannabinoid, for example by eliminating the cannabinoid aromatic ring that is derived from an alkylresorcylic acid in the naturally occurring cannabinoid pathway in Cannabis spp. Acetyl-CoA can also be produced as a result of this conversion.
[0065] These methods can be carried out in vivo or in vitro. When in vitro, the enzyme can be synthesized in a recombinant microorganism or plant and extracts of the microorganism or plant can be combined with the first cannabinoid. In various embodiments, the enzyme can be at least partially purified from the extract.
[0066] In these in vitro methods, the first cannabinoid can be present in a crude extract of a Cannabis sp. plant or a microorganism from which the first cannabinoid was synthesized. Alternatively, the first cannabinoid can be substantially purified when combined with the enzyme.
[0067] Exemplary in vitro methods are illustrated in
[0068] In other embodiments, bioconversion of THC to CBN takes place using lysate of a microbe containing the CBN synthase while the THC precursor is produced in a second microorganism. The first microbe could express the CBN synthase natively or recombinantly.
[0069] In additional embodiments, bioconversion of THC to CBN takes place using lysate of a microorganism containing the CBN synthase while the THC precursor is supplied as lysate from a second, cannabinoid producing microorganism. The first microbe could express the THC-to-CBN synthase natively or recombinantly.
[0070] In further embodiments, the CBN synthase is expressed recombinantly in a microbial host and the enzyme purified. The purified enzyme can then be used on purified plant derived THC to do an enzymatic conversion of THC to CBN in vitro.
[0071] The methods provided herein can facilitate development of industrial processes to eliminate THC and/or produce CBN in crude cannabinoid preparations, including plant material and microbial cell mass.
[0072] In the above exemplary embodiments, THC/A can be selectively degraded instead of being converted to CBN.
[0073] When the method is carried out in vivo, the method can be carried out by a living organism that synthesizes the enzyme. Any living organism can be utilized to carry out the method. In some embodiments, the method is carried out in a plant, e.g., a tobacco or Cannabis sp. plant.
[0074] In other embodiments, the method is carried out in a microorganism, as illustrated in
[0075] The microorganism can also comprise a recombinant enzyme “upstream” from cannabinoid synthase, e.g., a recombinant geranyl pyrophosphate synthase (GPPS) (see U.S. Provisional Patent Application 63/141,486). In various embodiments, the microorganism further comprises a recombinant GPPS and cannabinoid synthase, where the cannabinoid synthase can combine a polyprenyl pyrophosphate with alkylresorcylic acid to create a cannabinoid.
[0076] In some in vivo embodiments of these methods where the enzyme is in a first microorganism (yeast or bacteria), the first cannabinoid is synthesized in a second microorganism, wherein the method further comprises incubating the first microorganism, or an extract thereof, with the second microorganism. This is illustrated in
[0077] In other embodiments, the first cannabinoid is synthesized in a Cannabis sp. plant and matter from the Cannabis sp. plant is incubated with the first microorganism. This is illustrated in
[0078] In embodiments described above where the first cannabinoid is extracted from the second microorganism or a plant (e.g., a Cannabis sp. plant or tobacco), the first cannabinoid can be in a crude extract or can be partially or substantially purified from the second microorganism.
[0079] Various additional in vivo scenarios are illustrated in
[0080] Nonlimiting examples of enzymes that can be utilized in these reactions are provided in Table 1, where SEQ ID NOs:1-50 provide nucleic acid sequences for the enzymes, codon optimized for expression in yeast, and SEQ ID NOs:51-100 provide corresponding amino acid sequences. SEQ ID NOs:1-12 and 51-62 are P450 nucleic acid and amino acid sequences, respectively; SEQ ID NOs:13-20 and 63-70 are CPR nucleic acid and amino acid sequences, respectively; SEQ ID NOs:21-28 and 71-78 are CBN synthase nucleic acid and amino acid sequences, respectively; SEQ ID NOs:29-38 and 79-88 are THC degradase nucleic acid and amino acid sequences, respectively; and SEQ ID NOs:39-50 and 89-100 are oxidase nucleic acid and amino acid sequences, respectively. Of the oxidase enzymes provided, those comprising nucleic acid sequences SEQ ID NOs:42-50 and amino acid sequences SEQ ID NO:92-100 are laccases.
TABLE-US-00001 TABLE 1 Summary of codon optimized sequences provided herewith. Codon Optimized Amino Acid Nucleic Acid Sequence for Shorthand Sequence Isolated Protein p450_1 SEQ ID NO: 1 SEQ ID NO: 51 p450_2 SEQ ID NO: 2 SEQ ID NO: 52 p450_3 SEQ ID NO: 3 SEQ ID NO: 53 p450_4 SEQ ID NO: 4 SEQ ID NO: 54 p450_5 SEQ ID NO: 5 SEQ ID NO: 55 p450_6 SEQ ID NO: 6 SEQ ID NO: 56 p450_7 SEQ ID NO: 7 SEQ ID NO: 57 p450_8 SEQ ID NO: 8 SEQ ID NO: 58 p450_9 SEQ ID NO: 9 SEQ ID NO: 59 p450_10 SEQ ID NO: 10 SEQ ID NO: 60 p450_11 SEQ ID NO: 11 SEQ ID NO: 61 p450_12 SEQ ID NO: 12 SEQ ID NO: 62 CPR_1 SEQ ID NO: 13 SEQ ID NO: 63 CPR_2 SEQ ID NO: 14 SEQ ID NO: 64 CPR_3 SEQ ID NO: 15 SEQ ID NO: 65 CPR_4 SEQ ID NO: 16 SEQ ID NO: 66 CPR_5 SEQ ID NO: 17 SEQ ID NO: 67 CPR_6 SEQ ID NO: 18 SEQ ID NO: 68 CPR_7 SEQ ID NO: 19 SEQ ID NO: 69 CPR_8 SEQ ID NO: 20 SEQ ID NO: 70 CBNsyn_1 SEQ ID NO: 21 SEQ ID NO: 71 CBNsyn_2 SEQ ID NO: 22 SEQ ID NO: 72 CBNsyn_3 SEQ ID NO: 23 SEQ ID NO: 73 CBNsyn_4 SEQ ID NO: 24 SEQ ID NO: 74 CBNsyn_5 SEQ ID NO: 25 SEQ ID NO: 75 CBNsyn_6 SEQ ID NO: 26 SEQ ID NO: 76 CBNsyn_7 SEQ ID NO: 27 SEQ ID NO: 77 CBNsyn_8 SEQ ID NO: 28 SEQ ID NO: 78 THCdeg_1 SEQ ID NO: 29 SEQ ID NO: 79 THCdeg_2 SEQ ID NO: 30 SEQ ID NO: 80 THCdeg_3 SEQ ID NO: 31 SEQ ID NO: 81 THCdeg_4 SEQ ID NO: 32 SEQ ID NO: 82 THCdeg_5 SEQ ID NO: 33 SEQ ID NO: 83 THCdeg_6 SEQ ID NO: 34 SEQ ID NO: 84 THCdeg_7 SEQ ID NO: 35 SEQ ID NO: 85 THCdeg_8 SEQ ID NO: 36 SEQ ID NO: 86 THCdeg_9 SEQ ID NO: 37 SEQ ID NO: 87 THCdeg_10 SEQ ID NO: 38 SEQ ID NO: 88 Oxid_1 SEQ ID NO: 39 SEQ ID NO: 89 Oxid_2 SEQ ID NO: 40 SEQ ID NO: 90 Oxid_3 SEQ ID NO: 41 SEQ ID NO: 91 Oxid_4 SEQ ID NO: 42 SEQ ID NO: 92 Oxid_5 SEQ ID NO: 43 SEQ ID NO: 93 Oxid_6 SEQ ID NO: 44 SEQ ID NO: 94 Oxid_7 SEQ ID NO: 45 SEQ ID NO: 95 Oxid_8 SEQ ID NO: 46 SEQ ID NO: 96 Oxid_9 SEQ ID NO: 47 SEQ ID NO: 97 Oxid_10 SEQ ID NO: 48 SEQ ID NO: 98 Oxid_11 SEQ ID NO: 49 SEQ ID NO: 99 Oxid_12 SEQ ID NO: 50 SEQ ID NO: 100
Enzymes
[0081] Also provided is a non-naturally occurring enzyme that can modify a first cannabinoid into a second cannabinoid or a non-cannabinoid.
[0082] The non-naturally occurring enzyme in these embodiments can have any alterations from a naturally occurring counterpart. In some embodiments, the enzyme comprises at least one amino acid that is not in a naturally occurring enzyme that has the same enzymatic activity. In some of those embodiments, the enzyme comprises a conservative substitution of an amino acid in a naturally occurring enzyme that has the same enzymatic activity. In various embodiments, the naturally occurring enzyme comprises any of SEQ ID NOs:51-100.
[0083] These enzymes can be utilized in the above-described methods. As such, in some embodiments, the first and/or second cannabinoid comprises the structure
##STR00003##
where R.sub.1═CH.sub.3, CH.sub.2CH.sub.3, (CH.sub.2).sub.2CH.sub.3, (CH.sub.2).sub.3CH.sub.3, (CH.sub.2).sub.3CH.sub.3, (CH.sub.2).sub.4CH.sub.3, (CH.sub.2).sub.5CH.sub.3, or (CH.sub.2).sub.6CH.sub.3; R.sub.2═H or COOH; and R.sub.3═CH.sub.3 or CH.sub.2OH. In other embodiments, the enzyme is an aromatase, a dehydrogenase, an oxidase or a desaturase. In additional embodiments, the first cannabinoid is tetrahydrocannabinol (THC) or tetrahydrocannabinolic acid (THCA) and the second cannabinoid is cannabinol (CBN) or cannabinolic acid (CBNA) and the enzyme is an aromatase, a dehydrogenase, an oxidase or a desaturase. In further embodiments, the first cannabinoid is tetrahydrocannabivarinic acid (THCVA), tetrahydrocannabiphorolic acid (TCHPA), tetrahydrocannabiorcinic acid (THCOA) or sesquiTHCA (THCFA) and the second cannabinoid is cannabinerolic acid (CBNA), cannabinerovarinic acid (CBNVA), cannabiphorolic acid (CBNPA), cannabinorcinic acid (CBNOA) or sesqui cannabinerolic acid (sesqui-CBNA), respectively. Also, the first cannabinoid can be tetrahydrocannabivarinol (THCV), tetrahydrocannabiphorol (TCHP), tetrahydrocannabiorcinol (THCO) or sesquitetrahydrocannabinolic acid (sesquiTHCA) and the second cannabinoid can be cannabinerovarinol (CBNV), cannabiphorol (CBNP), cannabinorcinol (CBNO) or sesqui cannabinerol (sesqui-CBN), respectively.
[0084] Where the enzyme activity is the conversion of the first cannabinoid, e.g., THC, THCA, CBN or CBNA, into a 11-hydroxy analog, the enzyme can be a combination of a cytochrome P450 (CYP-450) and a cytochrome P450 reductase (CPR). In some of these embodiments, the CYP-450 is a CYP2C9 or a CYP3A4 or a CYP76AH22-24 or a CYP76AH1 (ferruginol synthases).
[0085] In various embodiments, the enzyme is expressed from a codon optimized gene sequence in a yeast or a bacterium, e.g. E. coli.
[0086] The enzyme can be in vivo (e.g., in a yeast, bacterium or plant), or in vitro. Nonlimiting examples of transgenic plants in which the enzyme can be expressed are a Cannabis sp. or a tobacco plant. Nonlimiting examples of transgenic yeast in which the enzyme can be expressed are species of Saccharomyces, Candida, Pichia, Schizosaccharomyces, Scheffersomyces, Blakeslea, Rhodotorula, or Yarrowia. In some embodiments, the enzyme is in a yeast that further comprises enzymes to synthesize the first cannabinoid.
Chemistry of the CBN Synthase Reaction
[0087] Chemically, the conversion of THC to CBN requires creation of 2 double bonds in a cyclohexene ring resulting in formation of an aromatic ring. See
[0088] Classes of enzymes that are capable of derivatizing cannabinoids and species that contain such enzymes are provided herewith. Multiple CBN synthase enzymes and enzymes specific for THC catabolism without production of CBN can be provided. Different enzymatic specificity is also envisioned, e.g. conversion of the acid derivative of THC (THCA) to CBNA. Derivatives of THC can also be converted to the appropriate derivatives of CBN, e.g. THCVA to CBVA. See
[0089] Also envisioned are enzymes of these classes that selectively degrade THC by converting it to molecules other than CBN but leave other cannabinoids untouched.
Enzyme Classes
[0090] The conversion of THC/A to CBN/A is an oxidation reaction, so it may be catalyzed by oxidases. CYP-450s are examples of enzymes of this reaction. Some oxygenases may add hydroxyl or ketone groups to the structure as they form the aromatic ring of CBN/A. This would generate a hydroxylated variant of CBN/A, a novel molecule. Oxidases may also include non P450s such as flavin-dependent monooxygenases, copper-dependent monooxygenases, bacterial polysaccharide monooxygenases, non-heme iron-dependent monooxygenases, pterin-dependent monooxygenases, diiron hydroxylases, alpha-ketoglutarate-dependent hydroxylases, other cofactor-dependent monooxygenases, cofactor-independent monooxygenases, and/or laccases (reviewed in Tones Pazmino, 2010).
[0091] An aromatic ring is formed by the CBN synthase, so it may also be catalyzed by aromatases (
[0092] As hydrogen atoms are abstracted to make the double bonds in CBN/A, a dehydrogenase may be able to catalyze the reaction. An example of a dehydrogenase that catalyzes a similar reaction would be arogenate dehydrogenase, as described here: https://www.uniprot.org/uniprot/Q944B6. Since double bonds are formed in creation of CBN/A, a desaturase may be responsible. An example of a desaturase that catalyzes a similar reaction would be arogenate dehydratase/prephenate dehydratase, as described at https://www.uniprot.org/uniprot/Q9LMR3
[0093] Some enzymes of these classes will also degrade THC by converting it to molecules other than CBN. A non-limiting example is reversing THCA synthase to generate CBGA.
[0094] In some embodiments, the CBN synthase can use any variant of tetrahydrocannabinolic acid THCA, as starting material, including: tetrahydrocannabivarinic acid (THCVA), tetrahydrocannabiphorolic acid (TCHPA), tetrahydrocannabiorcinic acid (THCOA), sesquiTHCA (THCFA) and produce, respectively, cannabinerolic acid (CBNA), cannabinerovarinic acid (CBNVA), cannabiphorolic acid (CBNPA), cannabinorcinic acid (CBNOA) sesqui cannabinerolic acid (sesqui-CBNA). Decarboxylation of any of these products, either enzymatically or by non-enzymatic methods such as heat, will produce the respective decarboxylated derivatives and is an optional last step of the pathway.
Organisms Originating the Enzymes
[0095] The enzyme can be a naturally occurring enzyme, or an enzyme derived from a naturally occurring enzyme, now known or later discovered, that occurs in any living organism, for example a bacterium, an archaeon, a protist, a fungus, an algae, an animal or a plant.
[0096] Many microbial enzymes catalyze reactions of these classes using similar substrates, but have never been tested for activity on cannabinoids. To determine a source of a CBN synthase, microbes can be screened for bioconversion activity of appropriate cannabinoids, after the methods of Abbott (1977). Microbes possessing this activity should have their genomes sequenced if there is no publicly available genome. Enzymes from the above listed enzyme classes should be found from the sequenced genomes and thereby identified as good candidates for the CBN synthase activity. Organisms that make molecules similar to desired cannabinoids can be identified from literature and those genomes searched as well to identify additional candidate enzymes. Bioinformatics methods to do this are in U.S. Pat. No. 10,671,632
[0097] Some microbes screened will contain a THC degradase instead of a CBN synthase. This is detectable as a reduction in a THC containing starting material relative to a negative control (
[0098] In some embodiments, the gene for the enzyme is derived from a bacterium. It is envisioned that an enzyme derived from any bacterium now known or later discovered can be utilized in the present invention. For example, the bacterium can be from phylum Abditibacteriota, including class Abditibacteria, including order Abditibacteriales; phylum Abyssubacteria or Acidobacteria, including class Acidobacteriia, Blastocatellia, Holophagae, Thermoanaerobaculia, or Vicinamibacteria, including order Acidobacteriales, Bryobacterales, Blastocatellales, Acanthopleuribacterales, Holophagales, Thermotomaculales, Thermoanaerobaculales, or Vicinamibacteraceae; phylum Actinobacteria, including class Acidimicrobiia, Actinobacteria, Actinomarinidae, Coriobacteriia, Nitriliruptoria, Rubrobacteria, or Thermoleophilia, including orders Acidimicrobiales, Acidothermales, Actinomycetales, Actinopolysporales, Bifidobacteriales, Nanopelagicales, Catenulisporales, Corunebacteriales, Cryptosporangiales, Frankiales, Geodermatophilales, Glycomycetales, Jiangellales, Micrococcales, Micromonosporales, Nakamurellales, Propionibacteriales, Pseudonocardiales, Sporichthyales, Streptomycetales, Streptosporangiales, Actinomarinales, Coriobacteriales, Eggerthellales, Egibacterales, Egicoccales, Euzebyales, Nitriliruptorales, Gaiellales, Rubrobacterales, Solirubrobacterales, or Thermoleophilales; phylum Aquificae, including class Aquificae, including order Aquificales or Desulfurobacteriales; phylum Armatimonadetes, including class Armatimonadia, including order Armatimonadales, Capsulimonadales, Chthonomonadetes, Chthonomonadales, Fimbriimonadia, or Fimbriimonadales; phylum Aureabacteria or Bacteroidetes, including class Armatimonadia, Bacteroidia, Chitinophagia, Cytophagia, Flavobacteria, Saprospiria or Sphingobacteriia, including order Bacteroidales, Marinilabiliales, Chitinophagales, Cytophagales, Flavobacteriales, Saprospirales, or Sphingopacteriales; phylum Balneolaeota, Caldiserica, Calditrichaeota, or Chlamydiae, including class Balneolia, Caldisericia, Calditrichae, or Chlamydia, including order Balneolales, Caldisericales, Calditrichales, Anoxychlamydiales, Chlamydiales, or Parachlamydiales; phylum Chlorobi or Chloroflexi, including class Chlorobia, Anaerolineae, Ardenticatenia, Caldilineae, Thermofonsia, Chloroflexia, Dehalococcoidia, Ktedonobacteria, Tepidiformia, Thermoflexia, Thermomicrobia, or Sphaerobacteridae, including order Chlorobiales, Anaerolineales, Ardenticatenales, Caldilineales, Chloroflexales, Herpetosiphonales, Kallotenuales, Dehalococcoidales, Dehalogenimonas, Kte donob acteral es, Thermogemmatisporales, Tepidiformales, Thermoflexales, Thermomicrobiales, or Sphaerobacterales; phylum Chrysiogenetes, Cloacimonetes, Coprothermobacterota, Cryosericota, or Cyanobacteria, including class Chrysiogenetes, Coprothermobacteria, Gloeobacteria, or Oscillatoriophycideae, including order Chrysiogenales, Coprothermobacterales, Chroococcidiopsidales, Gloeoemargaritales, Nostocales, Pleurocapsales, Spirulinales, Synechococcales, Gloeobacterales, Chroococcales, or Oscillatoriales; phyla: Eferribacteres, Deinococcus-thermus, Dictyoglomi, Dormibacteraeota, Elusimicrobia, Eremiobacteraeota, Fermentibacteria, or Fibrobacteres, including class Deferribacteres, Deinococci, Dictyoglomia, Elusimicrobia, Endomicrobia, Chitinispirillia, Chitinivibrionia, or Fibrobacteria, including order Deferribacterales, Deinococcales, Thermales, Dictyoglomales, Elusimicrobiales, Endomicrobiales, Chitinspirillales, Chitinvibrionales, Fibrobacterales, or Fibromonadales; phylum Firmicutes, Fusobacteria, Gemmatimonadetes, or Hydrogenedentes, including class Bacilli, Clostridia, Erysipelotrichia, Limnochordia, Negativicutes, Thermolithobacteria, Tissierellia, Fusobacteriia, Gemmatimonadetes, Longimicrobia, including order Bacillales, Lactobacillales, Borkfalkiales, Clostridiales, Halanaerobiales, Natranaerobiales, Thermoanaerobacterales, Erysipelotrichales, Limnochordales, Acidaminococcales, Selenomonadales, Veillonellales, Thermolithobacterales, Tissierellales, Fusobacteriales, Gemmatimonadales, or Longimicrobia; phylum Hydrogenedentes, Ignavibacteriae, Kapabacteria, Kiritimatiellaeota, Krumholzibacteriota, Kryptonia, Latescibacteria, LCP-89, Lentisphaerae, Margulisbacteria, Marinimicrobia, Melainabacteria, Nitrospinae, or Omnitrophica, including class Ignavibacteria, Kiritimatiellae, Krumholzibacteria, Lentisphaeria, Oligosphaeria, or Nitrospinae, including order Ignavibacteriales, Kiritimatiellales, Krumholzibacteriales, Lentisphaerales, Victivallales, Oligosphaerales, or Nitrospinia; phylum Omnitrophica or Planctomycetes, including class Brocadiae, Phycisphaerae, Planctomycetia, or Phycisphaerales, including order Sedimentisphaerales, Tepidisphaerales, Gemmatales, Isosphaerales, Pirellulales, or Planctomycetales; phylum Proteobacteria including class Acidithiobacillia, Alphaproteobacteria, Betaproteobacteria, Lambdaproteobacteria, Muproteobacteria, Deltaproteobacteria, Epsilonproteobacteria, Gammaproteobacteria, Hydrogenophilalia, Oligoflexia, or Zetaproteobacteria, including order Acidithiobacillales, Caulobacterales, Emcibacterales, Holosporales, Iodidimonadales, Kiloniellales, Kopriimonadales, Kordiimonadales, Magnetococcales, Micropepsales, Minwuiales, Parvularculales, Pelagibacterales, Rhizobiales, Rhodobacterales, Rhodospirillales, Rhodothalassiales, Rickettsiales, Sneathiellales, Sphingomonadales, Burkholderiales, Ferritrophicales, Ferrovales, Neisseriales, Nitrosomonadales, Procabacteriales, Rhodocyclales, Bradymonadales, Acidulodesulfobacterales, Desulfarculales, Desulfobacterales, Desulfovibrionales, Desulfurellales, Desulfuromonadales, Myxococcales, Syntrophobacterales, Campylobacterales, Nautiliales, Acidiferrobacterales, Aeromonadales, Alteromonadales, Arenicellales, Cardiobacteriales, Cellvibrionales, Chromatiales, Enterobacterales, Immundisolibacterales, Legionellales, Methylococcales, Nevskiales, Oceanospirillales, Orbales, Pasteurellales Pseudomonadales, Salinisphaerales, Thiotrichales, Vibrionales, Xanthomonadales, Hydrogenophilales, Bacteriovoracales, Bdellovibrionales, Oligoflexales, Silvanigrellales, or Mariprofundales; phylum Rhodothermaeota, Saganbacteria, Sericytochromatia, Spirochaetes, Synergistetes, Tectomicrobia, or Tenericutes, including class Rhodothermia, Spirochaetia, Synergistia, Izimaplasma, or Mollicutes, including order Rhodothermales, Brachyspirales, Brevinematales, Leptospirales, Spirochaetales, Synergistales, Acholeplasmatales, Anaeroplasmatales, Entomoplasmatales, or Mycoplasmatales; phylum Thermodesulfobacteria, Thermotogae, Verrucomicrobia, or Zixibacteria, including class Thermodesulfobacteria, Thermotogae, Methylacidiphilae, Opitutae, Spartobacteria, or Verrucomicrobiae, including order Thermodesulfobacteriales, Kosmotogales, Mesoaciditogales, Petrotogales, Thermotogales, Methylacidiphilales, Opitutales, Puniceicoccales, Xiphinematobacter, Chthoniobacterales, Terrimicrobium, or Verrucomicrobiales.
[0099] In other embodiments, the gene for the enzyme is derived from an archaeon. It is envisioned that an enzyme derived from any archaeon now known or later discovered can be utilized in the present invention. For example, the archaeon can be from phylum Euryarchaeota, including class Archaeoglobi, Hadesarchaea, Halobacteria, Methanobacteria, Methanococci, Methanofastidiosa, Methanomicrobia, Methanopyri, Nanohaloarchaea, Theionarchaea, Thermococci, or Thermoplasmata, including order Archaeoglobales, Hadesarchaeales, Halobacteriales, Methanobacteriales, Methanococcales, Methanocellales, Methanomicrobiales, Methanophagales, Methanosarcinales, Methanopyrales, Thermococcales, Methanomassiliicoccales, Thermoplasmatales, or Nanoarchaeales; DPANN superphylum, including subphyla Aenigmarcheota, Altiarchaeota, Diapherotrites, Micrarchaeota, Nanoarchaeota, Pacearchaeota, Parvarchaeota, or Woesearchaeota; TACK superphylum, including subphylum Korarchaeota, Crenarchaeota, Aigarchaeota, Geoarchaeota, Thaumarchaeota, or Bathyarchaeota; Asgard superphylum including subphylium Odinarchaeota, Thorarchaeota, Lokiarchaeota, Helarchaeota, or Heimdallarchaeota.
[0100] In additional embodiments, the gene for the enzyme is derived from a fungus. It is envisioned that a CBN synthase or THC degradase from any fungus now known or later discovered can be utilized in the present invention. This includes but is not limited to the phyla Chytridiomycota, Basidiomycota, Ascomycota, Blastocladiomycota, Ascomycota, Microsporidia, Basidiomycota, Glomeromycota, Symbiomycota, and Neocallimastigomycota. For example, the fungus can be from the phylum Ascomycota, including classes and orders Pezizomycotina, Arthoniomycetes, Coniocybomycetes, Dothideomycetes, Eurotiomycetes, Geoglossomycetes, Laboulbeniomycetes, Lecanoromycetes, Leotiomycetes, Lichinomycetes, Orbiliomycetes, Pezizomycetes, Sordariomycetes, Xylonomycetes, Lahmiales, Itchiclahmadion, Triblidiales, Saccharomycotina, Saccharomycetes, Taphrinomycotina, Archaeorhizomyces, Neolectomycetes, Pneumocystidomycetes, Schizosaccharomycetes, Taphrinomycetes; phylum Basidiomycota including subphyla or classes Pucciniomycotina, Ustilaginomycotina, Wallemiomycetes, and Entorrhizomycetes; subphylum Agaricomycotina including classes Tremellomycetes, Dacrymycetes, and Agaricomycetes; phylum Symbiomycota, including class Entorrhizomycota; subphylum Ustilaginomycotina including classes Ustilaginomycetes and Exobasidiomycetes; phylum Glomeromycota including classes Archaeosporomycetes, Glomeromycetes, and Paraglomeromycetes; subphylum Pucciniomycotina including orders and classes: Pucciniomycotina, Cystobasidiomycetes, Agaricostilbomycetes, Microbotryomycetes, Atractiellomycetes, Classiculomycetes, Mixiomycetes, and Cryptomycocolacomycetes; subphylum incertae sedis Mucoromyceta including orders Calcarisporiellomycota and Mucoromycota; phylum Mortierellomyceta including class Mortierellomycota; subphylum incertae sedis Entomophthoromycotina including order Entomophthorales; phylum Zoopagomyceta including classes Basidiobolomycota, Entomophthoromycota, Kickxellomycota, and Zoopagomycotina; subphylum incertae sedis Mucoromycotina including orders Mucorales, Endogonales, and Mortierellales; phylum Neocallimastigomycota including class Neocallimastigomycetes; phylum Blastocladiomycota including classes Physodermatomycetes and Blastocladiomycetes; phylum Rozellomyceta including classes Rozellomycota and Microsporidia; phylum Aphelidiomyceta including class Aphelidiomycota; Chytridiomyceta including classes Chytridiomycetes and Monoblepharidomycetes; and phylum Oomycota including classes or orders Leptomitales, Myzocytiopsidales, Olpidiopsidales, Peronosporales, Pythiales, Rhipidiales, Salilagenidiales, Saprolegniales, Sclerosporales, Anisolpidiales, Lagenismatales, Rozellopsidales, and Haptoglossales.
Nucleic Acids
[0101] The present invention is additionally directed to nucleic acids encoding any of the above-identified enzymes. In some embodiments, the nucleic acids are codon optimized to improve expression, e.g., using techniques as disclosed in U.S. Pat. No. 10,435,727. In some of these embodiments, the codon optimized nucleic acids comprise any of SEQ ID NOs:1-50.
[0102] More specifically, optimized nucleotide sequences are generated based on a number of considerations: (1) For each amino acid of the recombinant polypeptide to be expressed, a codon (triplet of nucleotide bases) is selected based on the frequency of each codon in the Saccharomyces cerevisiae genome; the codon can be chosen to be the most frequent codon or can be selected probabilistically based on the frequencies of all possible codons. (2) In order to prevent DNA cleavage due to a restriction enzyme, certain restriction sites are removed by changing codons that cover those sites. (3) To prevent low-complexity regions, long repeats (sequences of any single base longer than five bases) are modified. (2) and (3) are performed recursively to ensure that codon modification does not lead to additional undesirable sequences. (4) A ribosome binding site is added to the N-terminus. (5) A stop codon is added.
[0103] In various embodiments, the nucleic acids further comprise additional nucleic acids encoding amino acids that are not part of the enzyme. In some of these embodiments, the additional sequences encode additional amino acids present when the nucleic acid is translated, encoding, for example, an additional protein domain, with or without a linker sequence, creating a fusion protein. Other examples are localization sequences, i.e., signals directing the localization of the folded protein to a specific subcellular compartment or membrane.
[0104] In some embodiments, the nucleic acids have, at the 5′ end, a nucleic acid encoding codon optimized cofolding peptides to create a fusion protein, e.g., having SEQ ID NOs:69-73 (Table 2), joining the sequences together to form a fusion polypeptide, e.g., having the amino acid sequence of SEQ ID NO:74-78 fused at the N terminus of the enzyme polypeptide, generating recombinant fusion polypeptides.
TABLE-US-00002 TABLE 2 Codon Optimized Amino Acid Nucleic Acid Sequence for NAME Sequence Isolated Protein MBP Seq. ID NO: 101 Seq. ID NO: 106 VEN Seq. ID NO: 102 Seq. ID NO: 107 MST Seq. ID NO: 103 Seq. ID NO: 108 OSP Seq. ID NO: 104 Seq. ID NO: 109 OLE Seq. ID NO: 105 Seq. ID NO: 110
[0105] Further provided is a non-naturally occurring nucleic acids that encode an enzyme having the enzymatic activity of any of the non-naturally occurring enzymes described above, or a naturally occurring enzyme having any of the enzyme activities described above. The nucleic acids may be codon optimized, e.g., for production in yeast.
[0106] In some embodiments, the nucleic acid comprises additional nucleotide sequences that are not translated. Examples include promoters, terminators, barcodes, Kozak sequences, targeting sequences, and enhancer elements. Particularly useful here are promoters that are functional in yeast.
[0107] Expression of a gene encoding an enzyme is determined by the promoter controlling the gene. In order for a gene to be expressed, a promoter must be present within 1,000 nucleotides upstream of the gene. A gene is generally cloned under the control of a desired promoter. The promoter regulates the amount of enzyme expressed in the cell and also the timing of expression, or expression in response to external factors such as sugar source.
[0108] Any promoter now known or later discovered can be utilized to drive the expression of the various genes (e.g., 11-OH hydroxylase, CBN synthase, THC degradase) described herein. See e.g. http://parts.igem.org/Yeast for a listing of various yeast promoters. Exemplary promoters listed in Table 3 below drive strong expression, constant gene expression, medium or weak gene expression, or inducible gene expression. Inducible or repressible gene expression is dependent on the presence or absence of a certain molecule. For example, the GAL1, GAL 7, and GAL10 promoters are activated by the presence of the sugar galactose and repressed by the presence of the sugar glucose. The HO promoter is active and drives gene expression only in the presence of the alpha factor peptide. The HXT1 promoter is activated by the presence of glucose while the ADH2 promoter is repressed by the presence of glucose.
TABLE-US-00003 TABLE 3 Exemplary yeast promoters Strong Medium and weak Inducible/ constitutive constitutive repressible promoters promoters promoters TEF1 STE2 GAL1 PGK1 TPI1 GAL7 PGI1 PYK1 GAL10 TDH3 HO HXT1 ADH2
[0109] In various embodiments, the nucleic acid is in a yeast expression cassette. Any yeast expression cassette capable of expressing the enzyme in a yeast cell can be utilized. In some embodiments, the expression cassette consists of a nucleic acid encoding a CBN synthase or THC degradase with a promoter.
[0110] Additional regulatory elements can also be present in the expression cassette, including restriction enzyme cleavage sites, antibiotic resistance genes, integration sites, auxotrophic selection markers, origins of replication, and degrons.
[0111] The expression cassette can be present in a vector that, when transformed into a host cell, either integrates into chromosomal DNA or remains episomal in the host cell. Such vectors are well-known in the art. See e.g. http://parts.igem.org/Yeast for a listing of various yeast vectors.
[0112] A nonlimiting example of a yeast vector is a yeast episomal plasmid (YEp) that contains the pBluescript II SK(+) phagemid backbone, an auxotrophic selectable marker, yeast and bacterial origins of replication and multiple cloning sites enabling gene cloning under a suitable promoter (see Table 3). Other exemplary vectors include pRS series plasmids.
Host Cells
[0113] The present invention is also directed to genetically engineered host cells that comprise the above-described nucleic acids. Such cells may be, e.g., any species of filamentous fungus, including but not limited to any species of Aspergillus, which have been genetically altered to produce precursor molecules, intermediate molecules, or cannabinoid molecules. Host cells may also be any species of bacteria, including but not limited to Escherichia, Corynebacterium, Caulobacter, Pseudomonas, Streptomyces, Bacillus, or Lactobacillus.
[0114] In some embodiments, the genetically engineered host cell is a yeast cell, which may comprise any of the above-described expression cassettes, and capable of expressing the recombinant enzyme encoded therein.
[0115] Any yeast cell capable of being genetically engineered can be utilized in these embodiments. Nonlimiting examples of such yeast cells include species of Saccharomyces, Candida, Pichia, Schizosaccharomyces, Scheffersomyces, Blakeslea, Rhodotorula, or Yarrowia.
[0116] These cells can achieve gene expression controlled by inducible promoter systems; natural or induced mutagenesis, recombination, and/or shuffling of genes, pathways, and whole cells performed sequentially or in cycles; overexpression and/or deletion of single or multiple genes and reducing or eliminating parasitic side pathways that reduce precursor concentration.
[0117] The host cells of the recombinant organism may also be engineered to produce any or all precursor molecules necessary for the biosynthesis of cannabinoids, including but not limited to olivetolic acid (OA), olivetol (OL), FPP and GPP, hexanoic acid and hexanoyl-CoA, malonic acid and malonyl-CoA, dimethylallylpyrophosphate (DMAPP) and isopentenylpyrophosphate (IPP) as disclosed in U.S. Pat. No. 10,435,727.
[0118] Construction of Saccharomyces cerevisiae strains expressing a cannabinoid modifying or degrading enzyme such as CBN synthase or THC degradase is carried out via expression of a gene which encodes for the enzyme. The gene encoding the enzyme can be cloned into vectors with the proper regulatory elements for gene expression (e.g. promoter, terminator) and the derived plasmid can be confirmed by DNA sequencing. As an alternative to expression from an episomal plasmid, the gene encoding the enzyme may be inserted into the recombinant host genome. Integration may be achieved by a single or double cross-over insertion event of a plasmid, or by nuclease-based genome editing methods, as are known in the art e.g. CRISPR, TALEN and ZFR. Strains with the integrated gene can be screened by rescue of auxotrophy and genome sequencing. See, e.g., Green and Sambrook (2012).
[0119] To produce the desired cannabinoid, each candidate polypeptide may be introduced into a host cell genetically modified to contain all necessary components for cannabinoid biosynthesis using standard yeast cell transformation techniques (Green and Sambrook, 2012). Cells are subjected to fermentation under conditions that activate the promoter controlling the candidate polypeptide (see, e.g., Table 3). The broth may be subsequently subjected to HPLC analysis (
[0120] In some embodiments, for recombinant enzyme purification, the gene encoding the enzyme is cloned into an expression vector such as the pET expression vectors from Novagen, transformed into a protease deficient strain of E. coli such as BL21 and expressed by induction with IPTG. The protein of interest may be tagged with a common tag to facilitate purification, e.g. hexahistidine, GST, calmodulin, TAP, AP, CAT, HA, FLAG, MBP etc. Coexpression of a bacterial chaperone such as dnaK, GroES/GroEL or SecY may help facilitate protein folding. See Green and Sambrook (2012).
[0121] Any of the enzymes described above can also be produced in transgenic plants, using techniques known in the art (see, e.g., Keshavareddy et al., 2018). In these embodiments, the above-described nucleic acid encoding the enzyme further comprises a promoter functional in a plant. In various embodiments, the nucleic acid is in a plant expression cassette. Any plant capable of being transformed with the nucleic acid can be utilized here. In some embodiments, the plant is a tobacco or a Cannabis sp. plant. Cannabis sp. that are transformed with a THC degradase are particularly useful, since such an enzyme expressed in Cannabis sp. plants grown for fiber could reduce the THC content to below the 0.3% current legal THC limit.
[0122] Preferred embodiments are described in the following examples. Other embodiments within the scope of the claims herein will be apparent to one skilled in the art from consideration of the specification or practice of the invention as disclosed herein. It is intended that the specification, together with the examples, be considered exemplary only, with the scope and spirit of the invention being indicated by the claims, which follow the examples.
[0123] Various methods and compositions provided in U.S. patent applications Ser. Nos. 16/553,103, 16/553,120, 16/558,973, 17/068,636 and 63/053,539; U.S. Pat. No. 10,435,727; and US Patent Publications 2020/0063170 and 2020/0063171 are utilized in the examples.
EXAMPLE 1
Expression of a Recombinant Fusion Polypeptides for THC/A Conversion, Degradation, and 11-Hydroxy Cannabinoid Variant Production in a Modified Host Organism
[0124] Construction of Saccharomyces cerevisiae strains expressing CBN synthase, THC degradase, P450, and/or CPR enzymes fused with N terminal cofolding peptides from Table 1, having SEQ ID NOs:106-110 to produce CBN/A from THC/A, and 11-hydroxy variants such as 11-OH CBN, is carried out via expression of a fusion gene of any codon optimized nucleic acid sequence SEQ ID NOs:101-105 combined at the 5′ end of a nucleic acid sequence encoding an enzyme that modifies a first cannabinoid into a second cannabinoid or non-cannabinoid. The fusion genes were cloned into vectors with the proper regulatory elements for gene expression (e.g. promoter, terminator) and the derived plasmid was confirmed by DNA sequencing. The fusion genes were also inserted into the recombinant host genome. Integration was achieved by a single or double cross-over insertion event of the plasmid. Strains with the integrated gene were screened by rescue of auxotrophy and genome sequencing.
EXAMPLE 2
Method of Growth of Host Cells
[0125] Modified host cells which yield cannabinoids such as THC/A, express recombinant (i) CBN synthase for THC/A conversion to CBN/A, (ii) p450 and CPR protein combinations (11-OH hydroxylases) for 11-OH hydroxy variants of cannabinoids such as 11-OH-THC, or (iii) a combination of CBN synthase and 11-OH hydroxylases for production of cannabinoids such as 11-OH-CBN. More specifically, the cannabinoid-producing strain expressing CBN synthases and/or 11-OH hydroxylases herein is grown in a feedstock as described in U.S. patent application Ser. No. 17/068,636. An example feedstock used for a modified host expressing the recombinant CBN synthase is growing the strain in a minimal-complete or rich culture media containing yeast nitrogen base, amino acids, vitamins, ammonium sulfate, and a carbon source, such as glucose or molasses. The feedstock is consumed by the modified host which expresses the recombinant CBN synthase with a cannabinoid biosynthesis pathway to convert the feedstock into (i) biomass, (ii) THC/A and 11-OH-THC variants thereof, (iii) CBN/A and 11-OH CBN, and variants thereof, or (iv) biomass and the cannabinoids products in (ii) and (iii). Strains expressing the recombinant CBN synthase genes can be grown on feedstock for 12 to 160 hours at 25-37° C. for isolation of products.
EXAMPLE 3
Removal of THC/A by Formation of a Homopolymer or Heteropolymer
[0126] Cells are genetically engineered to contain one or more laccase enzymes. Integration is achieved by a single or double cross-over insertion event of the plasmid. Strains with the integrated gene are screened by rescue of auxotrophy and genome sequencing. The laccase gene can be under the control of an inducible promoter. When polymerization of THC/A is desired, inducer is added to the culture along with supplemental copper at a final concentration of 100 μM-100 mM. Polymerized cannabinoids can be separated from the culture by filtration, centrifugation or dialysis. Membranes for filtration and dialysis should be selected such that molecules corresponding to the size of a monomeric cannabinoid pass through the pores of the membrane, but larger molecules such as polymers are retained on the other side of the membrane.
EXAMPLE 4
Purification of Recombinant CBN Synthase and THC Degradase Enzymes for THC/A Conversion or Degradation
[0127] The CBN synthase or THC degradase enzyme is cloned into a high-copy vector with key features that allow 1) tight induction by the lactose analog, β-D-thiogalactoside (IPTG), 2) an N-terminal secretory signal peptide (e.g., MKKTAIAIAVALAGFATVAQA), and 3) C-terminal fusion to a HIS tag for purification. E. coli cells harboring the CBN synthase or THC degradase expression vector are grown in M9 minimal media with 1% glucose for 18 h at 37° C. and shaking at 300 rpm. Concentrated cell culture is diluted to an OD.sub.600=1 in fresh M9 minimal media with 1% glucose and 0.2 mM IPTG and grown for 48 h.
[0128] The supernatant containing the recombinant proteins is equilibrated in binding buffer (50 mM sodium phosphate, 0.5 M NaCl, 20 mM imidazole, 1 mM MgCl.sub.2, 10% glycerol, 10 mM 2-mercaptoethanol, 1 mM PMSF, Complete EDTA-free (1 tablet/100 ml), 20 mM 1-phenyl-2-thiourea; pH 7.4) and centrifuged at 2,500 g for 5 min to remove insoluble matter. Then the supernatant is filtered through a 0.45 μm filter (Millipore, MA, USA) and applied onto a HisTrap HP column (GE Healthcare Bioscience). The recombinant proteins are eluted with a step gradient of imidazole (concentrations of 5, 20, 40 and 300 mM). Fractions are analyzed by SDS-PAGE.
[0129] Purified CBN synthase or THC degradase protein is resuspended in activity buffer [100 mM sodium phosphate buffer, pH 6.55, 1 mM PMSF, EDTA-free protease inhibitor cocktail at working concentration (Roche, Meylan, France)] for use in converting or degrading THC/A in crude plant matter or THC/A in cannabinoid isolate via incubation and continuous shaking for 6-12 hrs at 30° C.
EXAMPLE 5
Preparation of Cell Lysate from a Host Expression Recombinant CBN Synthase and THC Degradase for Conversion and Degradation of THC/A
[0130] Host cells expressing recombinant CBN synthase or THC degradase are resuspended in lysis buffer consisting of 50 mM Tris-HCl pH7.5, 200 mM NaCl, 1 mM MgCl.sub.2, 5 mM DTT, 1 mM PMSF, and DNAse. Resuspended host cells are then lysed by sonication/French press/homogenization or enzymatic lysis such as zymolyase or lysozyme. Lysate is cleared by centrifugation at 16000 rpm for 15 min at 4° C. Cleared lysate is added to crude or purified cannabinoid preparations at concentrations ranging from 1 mg/gram to 1 g/g. The mixture is incubated with continuous shaking for 6-12 hrs at 30° C. Cannabinoids are then extracted.
EXAMPLE 6
Detection of Isolated Product
[0131] To identify cannabinoid conversion products from CBN synthase, the degradation of THC via THC degradase, 11-hydroxy variants of cannabinoids, and all other products of converted plant matter, cannabinoid isolate, or from a host cell expressing an engineered biosynthetic pathway for cannabinoids, an Agilent 1100 series liquid chromatography (LC) system equipped with a reverse phase C18 column (Agilent Eclipse Plus C18, Santa Clara, Calif., USA) was used. A gradient was used of mobile phase A (ultraviolet (UV) grade H.sub.2O+0.1% formic acid) and mobile phase B (UV grade acetonitrile+0.1% formic acid). Column temperature was set at 30° C. Compound absorbance was measured at 210 nm and 305 nm using a diode array detector (DAD) and spectral analysis from 200 nm to 400 nm wavelengths. A 0.1 milligram (mg)/milliliter (mL) analytical standard was made from certified reference material for each terpene and cannabinoid (Cayman Chemical Company, USA). Each sample was prepared by diluting 1) fermentation biomass from a recombinant host expressing the engineered cannabinoid and CBN synthase biosynthesis pathway or 2) a conversion or degradation reaction containing CBN synthase or THC degradase by 1:3 or 1:20 in 100% acetonitrile and filtered in 0.2 um nanofilter vials. The retention time and UV-visible absorption spectrum (i.e., spectral fingerprint) of the samples were compared to the analytical standard retention time and UV-visible spectra (i.e. spectral fingerprint) when identifying the terpene and cannabinoid compounds.
[0132]
[0133]
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[0161] In view of the above, it will be seen that several objectives of the invention are achieved and other advantages attained.
[0162] As various changes could be made in the above methods and compositions without departing from the scope of the invention, it is intended that all matter contained in the above description and shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense.
[0163] All references cited in this specification, including but not limited to patent publications and non-patent literature, and references cited therein, are hereby incorporated by reference. The discussion of the references herein is intended merely to summarize the assertions made by the authors and no admission is made that any reference constitutes prior art. Applicants reserve the right to challenge the accuracy and pertinence of the cited references.
[0164] As used herein, in particular embodiments, the terms “about” or “approximately” when preceding a numerical value indicates the value plus or minus a range of 10%. Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range is encompassed within the disclosure. That the upper and lower limits of these smaller ranges can independently be included in the smaller ranges is also encompassed within the disclosure, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the disclosure.
[0165] The indefinite articles “a” and “an,” as used herein in the specification and in the embodiments, unless clearly indicated to the contrary, should be understood to mean “at least one.”
[0166] The phrase “and/or,” as used herein in the specification and in the embodiments, should be understood to mean “either or both” of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Multiple elements listed with “and/or” should be construed in the same fashion, i.e., “one or more” of the elements so conjoined. Other elements can optionally be present other than the elements specifically identified by the “and/or” clause, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, a reference to “A and/or B”, when used in conjunction with open-ended language such as “comprising” can refer, in one embodiment, to A only (optionally including elements other than B); in another embodiment, to B only (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc.
[0167] As used herein in the specification and in the embodiments, “or” should be understood to have the same meaning as “and/or” as defined above. For example, when separating items in a list, “or” or “and/or” shall be interpreted as being inclusive, i.e., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items. Only terms clearly indicated to the contrary, such as “only one of” or “exactly one of,” or, when used in the embodiments, “consisting of,” will refer to the inclusion of exactly one element of a number or list of elements. In general, the term “or” as used herein shall only be interpreted as indicating exclusive alternatives (i.e. “one or the other but not both”) when preceded by terms of exclusivity, such as “either,” “one of” “only one of” or “exactly one of.” “Consisting essentially of,” when used in the embodiments, shall have its ordinary meaning as used in the field of patent law.
[0168] As used herein in the specification and in the embodiments, the phrase “at least one,” in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements. This definition also allows that elements can optionally be present other than the elements specifically identified within the list of elements to which the phrase “at least one” refers, whether related or unrelated to those elements specifically identified. Thus, as a non-limiting example, “at least one of A and B” (or, equivalently, “at least one of A or B,” or, equivalently “at least one of A and/or B”) can refer, in one embodiment, to at least one, optionally including more than one, A, with no B present (and optionally including elements other than B); in another embodiment, to at least one, optionally including more than one, B, with no A present (and optionally including elements other than A); in yet another embodiment, to at least one, optionally including more than one, A, and at least one, optionally including more than one, B (and optionally including other elements); etc
TABLE-US-00004 SEQ ID NOs >p450_1 Seq. ID NO: 1 ATGGCCGCAGACAGTCTTGTTGTCCTTGTTCTGTGCCTTAGTTGCCTTTTGCTGCTAT CTCTTTGGAGACAATCATCAGGGAGAGGTAAACTTCCGCCTGGACCAACTCCACTAC CCGTCATAGGGAATATATTACAAATCGGTATAAAGGACATCTCCAAGTCCCTGACGA ATCTTTCCAAGGTGTATGGTCCTGTGTTCACACTATACTTCGGCTTGAAACCCATCGT GGTCTTACATGGCTACGAGGCAGTGAAAGAGGCCCTGATTGATTTGGGGGAAGAGT TCAGTGGGAGAGGAATCTTTCCCCTTGCTGAGAGGGCTAATCGTGGTTTTGGGATAG TGTTTTCTAACGGAAAGAAGTGGAAAGAAATAAGGCGTTTCAGCCTGATGACTTTGC GTAATTTTGGGATGGGAAAAAGGTCAATTGAAGATCGTGTTCAAGAAGAAGCCCGT TGCCTGGTGGAGGAGTTGAGAAAGACGAAGGCTTCCCCGTGCGATCCAACTTTCATA CTGGGATGTGCGCCATGCAATGTCATATGTAGTATAATCTTTCATAAGAGATTCGAC TATAAGGATCAGCAATTCTTGAACTTGATGGAGAAATTGAACGAGAACATAAAAAT TCTGTCTTCCCCCTGGATTCAAATATGTAATAACTTTAGCCCAATAATAGACTACTTC CCAGGTACGCACAATAAACTGTTAAAGAACGTCGCTTTTATGAAATCTTACATATTG GAGAAGGTGAAAGAGCACCAAGAGAGCATGGACATGAACAATCCGCAAGACTTCA TTGATTGTTTCCTGATGAAGATGGAAAAAGAAAAGCACAACCAGCCTTCTGAATTTA CGATTGAAAGCCTTGAAAATACTGCAGTCGATCTATTCGGAGCTGGCACAGAGACT ACCTCAACCACGTTAAGATATGCTTTGCTTTTACTACTGAAGCATCCAGAGGTGACT GCCAAGGTGCAAGAAGAGATCGAGAGGGTCATCGGAAGGAACCGTTCCCCGTGTAT GCAGGACAGGAGCCATATGCCTTACACAGACGCGGTTGTCCACGAAGTCCAGCGTT ACATAGATCTATTACCGACGTCACTACCCCACGCGGTCACTTGTGACATCAAATTTC GTAACTACCTGATCCCCAAGGGCACTACCATATTAATTTCACTTACTTCCGTGCTACA CGACAATAAGGAATTTCCAAATCCCGAGATGTTCGACCCGCATCACTTTCTGGACGA AGGGGGAAATTTCAAGAAGTCAAAGTACTTCATGCCTTTCTCCGCCGGAAAGAGAA TCTGTGTAGGAGAAGCTCTGGCGGGGATGGAACTATTCTTGTTTTTAACCTCAATAT TACAGAATTTTAACCTTAAATCCCTTGTAGATCCTAAGAATCTGGACACAACGCCTG TGGTTAACGGGTTCGCGTCCGTTCCGCCGTTTTACCAGTTATGCTTTATTCCCGTTTA A >p450_2 Seq. ID NO: 2 ATGGCCGCAGACTCTCTTGTTGTATTGGTATTATGCCTAAGCTGCTTGCTTCTATTAA GCCTATGGAGACAAAGCAGTGGGAGAGGGAAACTTCCGCCCGGACCAACTCCTCTA CCTGTAATCGGGAACATTTTACAAATCGGCATAAAAGATATCTCAAAAAGTTTAACA AATTTGTCCAAGGTGTACGGCCCGGTATTTACTCTTTACTTCGGATTGAAGCCGATA GTAGTTTTGCACGGCTATGAGGCCGTCAAGGAGGCACTTATAGACTTAGGAGAGGA GTTTTCTGGGAGGGGCATTTTCCCGCTTGCAGAGCGTGCAAATAGGGGGTTTGGGAT AGTGTTCTCAAATGGTAAGAAATGGAAAGAAATCAGGCGTTTTTCTCTGATGACCCT TAGGAACTTCGGAATGGGAAAGAGATCTATCGAAGACAGGGTCCAGGAGGAAGCCC GTTGCCTAGTAGAAGAACTTCGTAAGACGAAGGCTTCCCCATGTGACCCTACCTTTA TTCTAGGCTGTGCGCCGTGCAATGTCATATGTTCTATTATTTTTCATAAGAGATTCGA TTATAAGGATCAGCAGTTCCTGAATTTAATGGAGAAATTAAACGAGAATGTTAAAAT ACTTAGTTCACCTTGGATACAGATATGTAATAACTTTTCACCTATAATCGATTATTTT CCCGGAACTCATAACAAGCTCTTGAAGAATGTTGCTTTTATGAAGTCTTACATTTTA GAGAAAGTTAAAGAGCATCAGGAATCCATGGACATGAATAACCCACAGGATTTCAT TGACTGCTTCTTAATGAAAATGGAAAAGGAAAAGCATAACCAGCCAAGTGAGTTCA CTATTGAATCTCTTGAAAACACGGCTGTGGATCTGTTCGGAGCAGGAACCGAGACTA CGTCTACGACGCTGCGTTATGCGTTACTGCTATTACTGAAACATCCAGAAGTTACAG CGAAGGTACAAGAGGAGATCGAGAGGGTCATCGGAAGAAATAGGAGTCCCTGTATG CAAGATCGTTCTCATATGCCCTACACAGATGCAGTCGTTCATGAAGTGCAGAGATAT ATCGACTTGTTACCCACCTCCCTACCTCACGCAGTAACCTGCGATATCAAATTTAGG AATTATTTAATACCTAAAGGGACGACCATTCTGATAAGCCTAACATCAGTCTTGCAC GATAACAAGGAATTTCCGAACCCCGAGATGTTTGACCCACACCATTTCCTGGACGAG GGCGGGAACTTCAAGAAATCCAATTATTTTATGCCTTTCAGTGCTGGTAAGAGGATA TGCGTAGGAGAGGCTTTAGCCAGGATGGAGCTTTTCCTATTCCTGACATCTATACTT CAAAACTTCAATCTAAAGAGTTTAGTCGATCCGAAAAATTTAGATACGACGCCTGTT GTAAATGGGTTCGCCTCCGTACCTCCCTTCTACCAATTGTGCTTTATTCCCGTGTAA >p450_3 Seq. ID NO: 3 ATGGCCGCAGATTCCTTTGTGGTGCTGGTGCTGTGTTTAAGCTGCTTATTGTTACTAT CCTTATGGCGTCAATCATCCGGACGTGGCAAATTGCCCCCTGGCCCAACACCCCTGC CCGTTATAGGAAATATACTTCAGATTGACATAAAAGATATCAGTAAATCCCTAACGA ATCTTTCTAAAGTTTATGGGCCCGTCTTTACCCTTTATTTCGGTCTGAAACCGATTGT CGTTTTACACGGATACGAGGCAGTGAAAGAGGCTCTGATCGACTTAGGTGAGGAGT TCTCTGGCCGTGGACATTTTCCATTGGCAGAACGTGCTAATAGGGGGTTCGGTATTG TATTCTCCAACGGGAAAAAGTGGAAGGAAATCAGGCGTTTTTCCTTAATGACGCTAA GAAACTTCGGCATGGGTAAGAGGAGTATAGAAGACCGTGTTCAAGAGGAAGCTAGA TGCTTAGTAGAGGAGCTGAGGAAGACTAAGGCCTCTCCCTGTGATCCAACATTCATT CTGGGCTGTGCTCCGTGCAATGTCATCTGTAGTATAATTTTTCGTAAGAGATTTGACT ATAAGGATCAACAGTTCCTGAATCTTATGGAGAAACTTAATGAAAATGTCAAGATA CTGTCTTCTCCCTGGATACAAATTTACAACAACTTTTCTCCCATCATAGATTACTTCC CTGGAACGCATAACAAGCTGTTGAAAAATGTGGCTTTTATGAAGTCCTATATTCTGG AAAAGGTCAAGGAACATCAGGAAAGTATGGACATGAACAATCCGCAAGATTTCATC GATTGCTTCTTAATGAAGATGGAGAAAGAAAAACATAATCAACCTAGTGAGTTTAC GATAGAGAGTCTTGAAAACACTGCCGCGGACCTATTCGGCGCCGGCACGGAAACCA CATCTACCACCCTTAGGTATGCATTACTTCTACTACTAAAACATCCTGAAGTTACCGC TAAGGTACAAGAAGAGATCGAGAGAGTAATAGGCAGGAATAGAAGTCCGTGTATGC AAGATAGGAGCCACATGCCATACACAGACGCAGTCGTCCATGAAGTTCAGCGTTAT ATTGACCTTCTTCCGACCAGTCTGCCACATGCAGTCACCTGTGACATTAAATTCAGG AATTATTTAATTCCCAAAGGTACAACAATATTAATCTCTCTGACGAGCGTTCTACAT GACAATAAGGAGTTCCCTAACCCAGAGATGTTCGATCCGCACCATTTCCTAGACGAA GGTGGAAACTTTAAGAAGAGCAATTATTTTATGCCATTCTCCGCTGGGAAAAGAATC TGTGTTGGCGAAGCATTGGCCAGAATGGAATTGTTTTTGTTCCTAACAAGCATCTTA CAAAATTTCAATCTTAAATCTTTGGTTGACCCGAAGAATCTGGACACCACACCTGTC GTAAATGGGTTTGCAAGCGTACCACCTTTTTATCAATTGTGTTTCATCCCCGTCTAA >p450_4 Seq. ID NO: 4 ATGGCCGCAGATCTGGTAGTGTTCTTGGCCTTGACCCTAAGCTGTTTAATTCTACTAT CATTATGGCGTCAGTCCTCCGGACGTGGTAAACTACCGCCAGGACCAACTCCGCTGC CCATTATCGGGAACTTTCTTCAAATCGACGTCAAAAACATATCACAATCATTTACAA ACTTCTCAAAAGCATACGGGCCAGTTTTTACTCTGTACCTAGGAAGCAAACCCACAG TTATTTTGCATGGCTACGAAGCTGTCAAGGAGGCGTTGATAGACAGAGGAGAAGAA TTTGCTGGGAGGGGAAGTTTCCCGATGGCCGAAAAGATCATCAAGGGATTTGGCGT CGTGTTTTCTAACGGCAATAGGTGGAAAGAAATGAGGAGATTCACATTGATGACTCT GAGGAACCTGGGTATGGGAAAGAGAAACATTGAAGATAGGGTCCAGGAGGAGGCA CAATGTTTGGTTGAAGAACTAAGAAAAACAAAAGGAAGTCCCTGTGATCCAACGTT CATTCTATCCTGCGCTCCCTGCAATGTTATCTGTTCTATTATATTCCAAAACCGTTTC GATTATAAAGATAAAGAATTTCTAATACTAATGGATAAAATTAACGAGAACGTGAA GATCCTATCCTCACCCTGGTTGCAAGTTTGCAATTCATTTCCTTCCTTAATAGACTAT TGTCCAGGTTCTCATCACAAAATAGTGAAAAATTTCAACTATTTAAAGTCTTATTTGC TGGAGAAAATTAAAGAGCATAAAGAGAGCCTTGACGTTACTAACCCCAGGGACTTT ATTGACTACTATTTAATTAAGCAGAAACAGGTTAACCATATTGAACAGTCAGAATTT TCTTTAGAGAATTTAGCCTCTACAATTAACGACCTGTTCGGGGCCGGGACAGAAACC ACGAGCACAACGCTGAGATACGCATTACTACTGCTACTTAAATATCCGGATGTTACT GCTAAGGTTCAGGAAGAAATCGATAGGGTAGTAGGACGTCATCGTTCACCATGCAT GCAAGATCGTTCACACATGCCTTATACTGATGCAATGATACACGAAGTTCAGCGTTT TATTGACTTGTTACCAACCAGTTTACCGCATGCGGTCACATGTGACATCAAATTTAG GAAATATCTGATCCCCAAGGGTACAACTGTCATCACTAGCCTAAGCTCCGTATTGCA TGACAGTAAAGAGTTCCCAAATCCAGAGATGTTCGACCCAGGGCACTTTTTGAATGC GAATGGCAATTTTAAGAAGAGCGACTATTTCATGCCCTTTAGCACTGGCAAGAGAAT ATGTGCCGGAGAGGGACTAGCAAGGATGGAATTATTCCTGATTCTTACCACAATACT ACAGAACTTCAAATTAAAATCATTAGTCCACCCAAAAGAGATAGATATTACTCCAGT GATGAACGGTTTTGCATCCCTTCCGCCACCCTACCAACTATGTTTTATTCCGCTTTAA >p450_5 Seq. ID NO: 5 AATGGCCGCAATTTTAGGCGTATTCCTTGGTTTGTTTTTGACGTGTTTACTATTGTTA AGTTTGTGGAAGCAGAATTTCCAAAGGAGAAATTTACCCCCAGGACCGACACCACT TCCCATTATCGGTAACATACTTCAAATCGACTTAAAGGACATTTCCAAGAGTTTGAG AAACTTCTCAAAAGTCTACGGCCCGGTATTTACCCTGTACTTGGGGAGGAAACCCGC GGTCGTTCTGCATGGTTACGAGGCTGTTAAAGAGGCACTTATCGATCACGGGGAAG AGTTCGCAGGTAGGGGTGTGTTTCCCGTCGCCCAAAAGTTTAACAAGAACTGCGGG GTGGTTTTCTCATCCGGCCGTACCTGGAAGGAAATGAGGAGATTCTCCTTGATGACA CTTAGGAATTTTGGGATGGGCAAGAGAAGTATAGAGGATAGGGTACAGGAAGAGGC ACGTTGTCTAGTAGACGAACTTCGTAAAACTAACGGGGTGCCTTGTGATCCAACCTT TATCCTGGGGTGCGCCCCGTGTAACGTGATTTGCTCTATCGTATTCCAAAACAGATT CGATTACAAAGACCAGGAGTTTCTTGCGCTAATAGATATACTAAATGAAAACGTTGA GATCCTTGGATCACCGTGGATTCAAATTTGTAATAACTTCCCAGCTATTATTGACTAT TTACCGGGAAGACACAGGAAACTGTTAAAGAACTTTGCTTTTGCGAAACATTACTTC TTAGCTAAAGTAATTCAACACCAGGAATCATTAGATATCAATAATCCCCGTGATTTC ATCGACTGCTTCCTTATAAAAATGGAGCAGGAGAAGCATAATCCCAAAACTGAGTTT ACTTGCGAGAACTTAATCTTCACTGCTTCTGACCTTTTCGCGGCCGGTACGGAGACA ACCTCTACTACACTTCGTTATTCCTTATTATTGTTGTTAAAGTACCCTGAGGTTACGG CAAAGGTGCAAGAAGAGATTGACCACGTGATAGGTCGTCACAGGTCTCCATGTATG CAAGACCGTCATCACATGCCGTACACAGACGCTGTACTGCACGAGATACAGCGTTA CATCGACCTATTACCCACGAGCTTACCTCACGCGCTTACCTGTGATATGAAGTTTAG GGATTATTTAATCCCGAAGGGAACTACCGTTATCGCTTCTTTAACTTCAGTGCTTTAC GATGATAAGGAGTTCCCTAACCCAGAGAAATTTGATCCAAGCCACTTCCTTGACGAG AACGGAAAATTCAAAAAGTCCGATTACTTCTTCCCGTTCTCTACTGGAAAAAGGATC TGCGTAGGAGAGGGGCTTGCTCGTACCGAATTGTTTCTATTCTTAACTACAATTCTGC AAAATTTTAACCTGAAGAGCCCTGTAGATCTGAAGGAGTTAGACACGAATCCTGTG GCAAACGGTTTTGTGTCAGTACCACCAAAATTTCAGATCTGTTTTATTCCTATATAA >p450_6 Seq. ID NO: 6 ATGGCCGCAGCATTGATACCAGACTTAGCGATGGAAACCTGGTTGTTGCTTGCGGTG TCTTTAGTCCTACTGTATCTATACGGTACTCATAGCCATGGTCTGTTCAAAAAGTTAG GTATCCCCGGTCCAACGCCGCTACCCTTCCTTGGTAATATTCTGTCTTATCATAAGGG TTTTTGCATGTTCGATATGGAGTGTCATAAGAAGTACGGTAAGGTATGGGGATTTTA TGACGGTCAGCAGCCAGTCTTGGCAATAACAGACCCGGACATGATCAAGACAGTCC TTGTAAAAGAGTGTTATAGCGTGTTTACGAACAGGAGACCGTTCGGGCCAGTGGGCT TCATGAAGTCCGCAATTTCTATTGCGGAAGATGAGGAGTGGAAAAGGCTTCGTAGTC TTTTGAGCCCTACATTTACGTCTGGAAAATTGAAGGAAATGGTCCCTATCATTGCTC AATACGGAGATGTTCTAGTGAGGAATTTAAGGAGAGAGGCTGAGACTGGAAAGCCG GTTACACTAAAAGACGTTTTCGGCGCGTACTCTATGGATGTCATCACCTCTACATCTT TCGGGGTAAACATCGACAGTCTGAATAACCCGCAAGACCCCTTTGTTGAGAACACA AAGAAATTACTGAGATTCGACTTTTTGGACCCGTTCTTTCTGTCCATTACTGTATTCC CCTTTTTGATTCCGATTCTGGAAGTTTTAAATATTTGTGTTTTCCCGCGTGAGGTTAC AAATTTCCTAAGGAAAAGTGTTAAAAGGATGAAGGAGTCCAGACTGGAAGATACTC AAAAGCATAGGGTAGATTTCCTACAATTAATGATTGACTCACAGAATAGTAAGGAG ACCGAGAGCCACAAGGCCCTTAGTGATCTTGAATTAGTCGCACAGTCAATTATTTTC ATATTTGCGGGCTACGAGACAACCAGCTCAGTTCTATCATTTATAATGTATGAACTG GCCACCCACCCTGATGTGCAACAAAAACTTCAGGAAGAGATCGATGCAGTCCTTCC AAATAAAGCTCCACCCACCTATGATACCGTTTTGCAAATGGAGTATCTTGACATGGT TGTAAACGAAACCCTGCGTTTGTTTCCTATAGCAATGAGATTGGAACGTGTATGTAA GAAAGACGTGGAGATAAATGGAATGTTTATTCCTAAAGGTGTGGTCGTTATGATTCC CTCATATGCCTTACATCGTGATCCAAAATATTGGACGGAGCCTGAAAAATTTCTGCC AGAGAGGTTTTCCAAGAAAAACAAAGATAATATAGATCCCTACATCTATACACCCTT TGGCAGCGGTCCGAGGAATTGCATTGGCATGCGTTTTGCTTTAATGAATATGAAGCT GGCCTTAATTAGGGTTTTGCAAAATTTCTCTTTCAAACCGTGCAAGGAAACTCAGAT ACCATTAAAACTTTCATTAGGAGGCCTACTTCAACCTGAGAAACCTGTGGTTTTAAA AGTTGAGAGTAGAGACGGTACGGTGAGTGGCGCTTAA >p450_7 Seq. ID NO: 7 ATGGCCGCAGATCTAATACCTAATCTAGCCGTAGAGACCTGGCTTCTGTTAACCAAA TTGGAGTTTGGGTTCTACATATTTCCGTTTATCTACGGTACTCATAGCCATGGTCTTT TCAAGAAACTGGGCATTCCAGGCCCGACGCCATTGCCGTTCCTGGGTAATATCCTAT CATACAGAAAAGGCTTCTGCATGTTTGACATGGAATGCCACAAGAAGTATGGGAAG GTATGGGGCTTTTACGATGGCAGACAACCAGTTCTGGCAATTACAGACCCGGACATG ATAAAAACGGTTCTAGTAAAGGAATGTTATTCTGTATTCACTAATAGGCGTCCTTTC GGCCCAGTGGGGTTCATGAAATCTGCGATATCTATCGCGGAAGATGAAGAGTGGAA GAGAATAAGATCTTTACTTAGCCCTACATTCACTAGTGGCAAATTGAAGGAGATGGT TCCTATTATTGCCCAGTACGGAGACGTCTTAGTACGTAATCTTAGAAGAGAAGCCGA TACCGGTAAGCCCGTTACACTGAAGGACGTCTTCGGAGCATACAGTATGGACGTGAT CACATCTACTTCTTTCGGTGTAAACATAGACTCCTTGAACAATCCCCAAGATCCCTTC GTTGAAAACACTAAGAAACTACTGAGATTTGACTTTTTGGACCCTTTCTTTCTATCTA TTATAGTCTTTCCTTTCTTGATTCCAATTCTGGAGGTACTGAATATCTGCGTATTTCCT CGTGAAGTCACAAACTTCCTAAGAAAGTCAGTCAAGAGGATGAAGGAAAGCCGGCT AGAAGACACTCAAAAGCATAGGGTTGACTTTCTTCAGTTAATGATTGATTCTCAAAA CTCCAAAGAAACTGAGAGTCACAAAGCTCTATCAGATCTGGAGTTAGTGGCGCAGT CCATAATTTTTATCTTTGCCGGTTACGAGACCACAAGTTCCGTGCTGTCATTTATCAT GTATGAGCTGGCTACCCACCCAGATGTGCAGCAAAAACTACAGGAGGAGATCGATG CAGTTTTACCCAATAAGGCACCGCCCACGTATGACACAGTTCTGCAAATGGAGTACC TGGACATGGTGGTCAATGAGACGCTTCGTTTGTTCCCAGTTGCTATGAGGTTGGAGA GGGTGTGCAAGAAGGATGTTGAGATAAACGGTATGTTTATCCCAAAGGGCGTTGTC GTGATGATACCAAGCTACGCACTTCACCGTGATCCTAAATATTGGACTGAGCCTGAG AAATTTTTACCTGAACGTTTTAGTAAGAAAAATAAAGATAACATTGATCCCTATATC TACACGCCTTTCGGAAGCGGACCCCGTAATTGTATAGGAATGAGGTTCGCTCTTATG AATATGAAATTAGCCCTAATACGTGTGCTACAAAACTTCAGCTTCAAGCCATGCAAG GAGACACAGATTCCCCTAAAGCTGCGTCTTGGGGGTTTGCTACAGCCGGAAAAACCT ATCGTTCTAAAAGTCGAAAGTAGGGATGGAACAGTGTCCGGGGCATAA >p450_8 Seq. ID NO: 8 ATGGCCGCAGCACTTATACCCGATTTAGCGATGGAGACGTGGTTACTACTAGCGGTG TCACTGGTGCTGCTGTACCTATATGGGACCCATAGTCATGGACTGTTCAAAAAGTTG GGCATTCCCGGACCGACGCCGCTACCCTTTCTTGGTAATATTTGGTCTTATCGTAAAG GATTCTGTATGTTCGACATGGAATGCCATAAGAAGTATGGGAAAGTTTGGGGGTTCT ATGATGGGAGACAGCCAGTTCTAGCTATCACTGATCCCGATATGATTAAAACAGTTC TTGTAAAAGAGTGTTATAGTGTCTTCACAAACCGTAGGCCTTTCGGCCCAGTCGGCT TTATGAAGTCTGCCATATCCATTGCTGAGGATGAGGAATGGAAGAGACTGAGATCC CTTTTGTCTCCGACCTTTACTAGCGGCAAGTTGAAGGAGATGGTACCATTGATCGCA CAATATGGCGACGTACTTGTCCGTAACCTGCGTTTAGAGGCCGAAACGGGCAAACC GGTTACGATGAAGGTTATTACTTCTACAAGTTTCGGGGTCAATATAGACTCACTGAA TAACCCACAAGATCCTTTCGTAGAGAATACTAAAAAGTTGCTGAGATTCGATTTCCT AGACCCCTTTTTCCTGTCTATTATTGTCTTTCCTTTCTTGACGCCTATACTTGAAGTAT TGAACATTAGTGTGTTCCCGAGGGCCGTTACTTCATTCTTGCGTAAAAGTGTTAAGA GAATGAAAGAGTCTAGGCTTGAAGATACTCAGAAACATCGTGTGGACTTCTTACAG CTAATGATTGACTCCCAAAATAGTAAGGAGACTGAGAGTCATAAAGCGTTAAGCGA CTTGGAATTGGTAGCACAAAGCATAATCTTCATCTTTGCTGGGTACGAGACGACTTC CAGCGTGCTGAGTTTTATAACATACGAATTGGCAACGCACCCGGACGTTCAGCAAA AACTTCAAGAGGAAATAGATGCCGTCTTGCCGAACAAGGCACCCCCGACTTATGAT ACAGTGTTGCAAATGGAGTACCTAGACATGGTAGTCAACGAGACACTTAGGTTATTT CCTATAGCCATGAGGTTAGAGAGAGTCTGCAAAAAGGACGTAGAGATTAATGGTAT GTTCATCCCGAAAGGAGTTGTAGTAATGATCCCTTCCTACGCCCTGCACCACGACCC TAAGTACTGGACCGAACCCGAAAAGTTCCTGCCCGAGCGTTTCTCTAAGAAAAATA AAGATAATATCGATCCCTATATTTATACACCATTCGGCTCTGGACCAAGGAACTGCA TTGGCATGCGTTTTGCCCTGATGAATATGAAGCTGGCGCTAATAAGGGTACTGCAGA ATTTTTCCTTTAAACCGTGCAAGGAAACCCAAATACCTCTAAAGTTACGTCTGGGAG GTCTGCTACAACCGGAAAAACCCATTGTCTTGAAAGTGGAATCCAGAGATGGCACC GTTTCTGGGGCGTAA >p450_9 Seq. ID NO: 9 ATGGCCGCAGAGTTAATTCCGTCCTTTTCTATGGAAACTTGGGTACTTCTAGCGACC AGTTTGGTCTTGTTATACATATACGGTACATATTCTTATGGTCTATTTAAAAAGTTAG GCATTCCGGGCCCGCGTCCCGTACCCTATTTTGGGTCTACTATGGCCTATCATAAGG GGATTCCGGAGTTCGATAACCAGTGTTTTAAGAAGTATGGCAAAATGTGGGGGTTTT ATGAAGGCCGTCAGCCTATGCTGGCAATCACAGACCCAGATATAATTAAAACGGTA CTGGTAAAAGAGTGTTACTCTGTATTCACTAACAGACGTATCTTCGGGCCTATGGGA ATAATGAAATACGCCATTTCTCTAGCATGGGACGAGCAATGGAAGCGTATCAGAAC CTTATTATCCCCGGCGTTTACTAGCGGCAAGTTAAAAGAAATGTTCCCTATTATCGG GCAGTACGGAGATATGTTGGTTAGGAACCTTCGTAAGGAAGCCGAGAAAGGTAACC CCGTTAATATGAAAGATATGTTTGGAGCCTACTCAATGGATGTTATCACAGGGACGG CTTTCGGGGTGAACATTGATAGTTTGAATAATCCCCACGACCCCTTCGTGGAGCATT CCAAGAATCTTCTAAGGTTCAGGCCCTTCGACCCATTTATCTTGAGCATTATCTTATT TCCGTTCCTAAACCCGGTGTTCGAAATATTAAACATTACTCTGTTTCCGAAGAGCAC TGTCGATTTCTTTACTAAATCTGTCAAGAAGATCAAAGAATCCAGACTAACCGATAA GCAGATGAATAGGGTGGATCTGTTACAGTTAATGATTAACTCTCAGAACTCAAAAG AAATAGATAACCACAAAGCCCTTAGCGACATCGAGCTAGTGGCCCAATCTACCATC TTTATCTTTGGAGGTTATGAAACCACAAGCTCAACATTGAGCTTTATTATCTACGAA CTGACAACGCATCCTCATGTACAACAGAAGGTACAGGAAGAAATTGACGCAACATT TCCAAACAAGGCACCACCCACCTATGATGCGTTGGTACAGATGGAGTACCTAGATAT GGTAGTGAACGAAACTTTGCGTATGTTTCCTATAGCTGGGCGTCTGGAAAGGGTCTG CAAGAAGGACGTCGAAATTCACGGGGTGACGATTCCTAAGGGAACGACCGTTCTAG TACCTTTATTTGTCCTACACAACAACCCAGAGCTTTGGCCTGAACCCGAGGAGTTCA GGCCTGAAAGGTTTTCTAAAAACAATAAGGACAGCATCAACCCGTATGTGTACCTAC CATTTGGCACAGGTCCTCGTAATTGCCTGGGTATGCGTTTTGCGATAATGAATATCA AATTAGCTCTAGTCCGTATTTTACAGAATTTCTCATTTAAACCATGCAAGGAGACGC AGATTCCTCTGAAGTTGTATACTCAGGGGTTGACTCAACCCGAACAACCAGTGATCT TGAAGGTGGTTCCGCGTGGTCTTGGCCCGCAGGTTGAACCCGACTTCCTTTAA >p450_10 Seq. ID NO: 10 ATGGCCGCAGATTCTTTTCCACTGCTGGCGGCATTGTTCTTCATCTTAGCTGCTACAT GGTTTATTAGCTTCCGTAGACCGAGGAACCTACCCCCAGGTCCATTCCCTTACCCAA TAGTAGGAAACATGTTGCAACTTGGCACACAACCACACGAAACGTTCGCAAAACTT TCCAAGAAGTATGGGCCACTAATGTCAATCCACTTGGGCTCCTTGTACACCGTAATA GTCAGCAGCCCAGAGATGGCTAAGGAGATTATGCATAAGTACGGCCAAGTCTTCTC AGGCCGTACAGTGGCGCAGGCGGTCCACGCGTGCGGGCATGATAAGATCAGCATGG GCTTTCTGCCGGTAGGGGGTGAGTGGCGTGATATGAGAAAGATTTGCAAAGAGCAA ATGTTCTCACACCAATCAATGGAGGATTCACAATGGCTGCGTAAGCAGAAATTACA GCAACTACTAGAATATGCTCAGAAGTGCTCAGAGAGGGGTAGAGCCATCGACATTA GGGAGGCAGCGTTTATCACCACTTTGAACTTGATGTCCGCCACTTTGTTCTCCATGCA GGCGACCGAATTCGATTCCAAGGTAACTATGGAATTTAAGGAGATTATAGAAGGAG TCGCCTCCATTGTGGGTGTACCAAACTTCGCAGATTATTTTCCTATTTTACGTCCCTT CGACCCCCAAGGGGTTAAAAGGCGTGCCGACGTATACTTCGGAAGACTTTTAGCCAT CATTGAGGGGTTCCTTAATGAAAGGGTGGAGAGTAGGAGGACGAACCCCAACGCAC CTAAAAAGGACGACTTCCTGGAAACGCTAGTTGATACCCTTCAGACTAATGACAATA AGCTAAAGACGGATCACTTGACTCATTTAATGCTGGACTTATTTGTGGGAGGTTCAG AAACTAGCACAACCGAGATAGAGTGGATTATGTGGGAGCTTCTAGCGAACCCGGAA AAGATGGCAAAAATGAAAGCTGAGTTGAAGTCAGTGATGGGTGAAGAGAAGGTTGT TGATGAAAGTCAGATGCCACGTTTGCCATATTTACAGGCAGTTGTTAAAGAAAGCAT GAGGTTACATCCACCAGGTCCATTGCTATTACCTAGAAAGGCCGAGTCCGACCAGGT CGTAAATGGCTATCTGATTCCGAAAGGGGCGCAGGTACTGATCAATGCCTGGGCGA TTGGAAGGGACCACTCAATCTGGAAAAACCCGGACTCCTTTGAACCGGAAAGATTC TTAGATCAGAAAATTGATTTTAAGGGCACCGATTACGAACTTATCCCCTTCGGGAGT GGCAGGAGAGTCTGTCCAGGAATGCCTCTTGCTAATAGGATCCTTCACACAGTCACT GCCACGCTAGTACATAATTTCGATTGGAAGCTTGAGCGTCCGGAGGCCTCAGACGCT CATAGGGGCGTGCTGTTCGGCTTTGCTGTAAGGAGAGCAGTCCCTCTAAAGATTGTG CCTTTTAAGGTG >p450_11 Seq. ID NO: 11 ATGGCAGCCGATCCCTTCCCTCTGGTAGCAGCGGCATTATTCATAGCTGCAACATGG TTCATTACCTTCAAAAGGAGACGTAATCTTCCGCCGGGGCCTTTCCCTTACCCGATTG TGGGCAATATGTTGCAACTAGGTTCCCAACCACACGAGACATTTGCCAAGCTATCCA AAAAGTACGGGCCATTAATGTCAATTCACCTTGGAAGTTTATATACCGTAATAATAT CCTCCCCCGAAATGGCCAAAGAGATAATGCACAAGTACGGGCAAGTCTTTTCTGGG AGAACAATAGCTCAGGCTGTGCACGCATGCGATCACGATAAAATATCTATGGGCTTT TTACCTGTGGGAGCAGAGTGGCGTGACATGAGGAAGATCTGCAAGGAACAGATGTT CTCTCATCAAAGCATGGAAGATAGTCAGAACTTACGTAAACAGAAACTTCAGCAAT TGCTGGAATATGCTCAAAAATGCAGTGAAGAAGGAAGAGGAATCGATATACGTGAG GCAGCTTTTATTACTACATTAAACCTGATGTCTGCCACGTTATTCAGCATGCAAGCC ACTGAATTCGATAGTAAAGTCACTATGGAGTTCAAGGAAATAATCGAAGGAGTGGC GAGCATCGTGGGCGTCCCAAATTTTGCAGATTATTTCCCCATTCTGCGTCCTTTCGAC CCTCAAGGGGTTAAGCGTCGTGCGGATGTCTACTTTGGAAGATTATTAGGCTTGATC GAAGGTTATCTTAACGAAAGAATTGAATTCAGAAAAGCCAACCCCAATGCCCCAAA GAAAGACGATTTTTTAGAAACCCTGGTGGACGCACTTGATGCGAAGGATTACAAAC TAAAGACTGAACACCTTACTCACCTGATGCTAGACCTATTCGTTGGGGGGAGCGAGA CGAGCACCACTGAAATTGAGTGGATCATGTGGGAGTTACTGGCATCACCTGAGAAG ATGGCCAAAGTCAAAGCAGAATTGAAAAGTGTAATGGGGGGCGAAAAGGTCGTGG ACGAGTCTATGATGCCTAGATTACCTTATCTGCAAGCAGTGGTTAAAGAGTCAATGA GGTTACACCCGCCAGGCCCATTATTACTTCCAAGAAAAGCGGAAAGTGACCAGGTC GTAAACGGTTATTTGATTCCTAAGGGAGCGCAAGTACTGATCAATGCGTGGGCGATG GGTAGAGACCCAAGCCTATGGAAAAACCCTGACTCTTTTGAGCCAGAGCGTTTTTTA GACCAGAAGATCGACTTTAAGGGTACAGATTACGAACTTATCCCGTTTGGAAGTGGC AGAAGGGTGTGCCCTGGAATGCCCCTGGCGAACAGAATTCTTCATACGGTTACTGCT ACTCTTGTGCATAACTTTGATTGGAAATTGGAAAGACCGGAGGCAAGCGACGCGCA CAAGGGAGTCCTTTTTGGTTTCGCGGTCAGGAGAGCTGTACCTTTGAAGATCGTCCC TATCAAGGCA >p450_12 Seq. ID NO: 12 ATGGCGGCAGACAGCTTCCCGTTACTGGCAGCACTTTTCTTTATCGCAGCAACTATA ACTTTCCTGTCTTTCAGGCGTAGAAGAAACTTGCCGCCCGGACCATTTCCCTACCCT ATTGTAGGTAATATGCTACAACTGGGTGCAAATCCACACCAAGTCTTCGCCAAACTT TCAAAAAGATATGGGCCTCTGATGAGTATACATCTGGGAAGCTTGTATACGGTTATA GTGAGTTCCCCTGAGATGGCGAAGGAAATATTACATAGGCATGGGCAAGTGTTCTCT GGTCGTACTATTGCCCAAGCTGTCCACGCTTGCGATCATGACAAAATATCTATGGGT TTCCTTCCAGTAGCCAGCGAATGGAGGGACATGAGGAAAATTTGCAAGGAGCAGAT GTTCAGCAATCAAAGCATGGAGGCTAGCCAGGGACTTCGTAGGCAGAAACTACAAC AACTTTTGGATCATGTACAGAAATGCTCCGATAGTGGGAGGGCCGTCGACATTAGA GAAGCTGCTTTCATAACCACCTTGAATCTTATGTCCGCCACACTGTTCAGCTCCCAG GCCACCGAGTTCGATTCTAAGGCTACCATGGAATTTAAGGAGATTATTGAAGGTGTA GCCACCATCGTAGGCGTACCTAACTTCGCAGATTACTTCCCAATTCTTAGGCCCTTTG ATCCCCAGGGAGTGAAACGTAGGGCCGACGTATTTTTCGGAAAACTGTTAGCCAAA ATTGAAGGCTATTTAAACGAGAGATTAGAATCCAAGAGGGCAAACCCGAATGCGCC AAAAAAGGACGATTTCTTGGAGATTGTCGTCGATATTATCCAGGCAAACGAATTTAA GTTAAAGACTCACCACTTTACTCACTTGATGTTGGACTTATTTGTTGGCGGCTCAGAC ACGAATACAACGTCCATCGAGTGGGCGATGTCTGAGTTAGTAATGAACCCCGACAA GATGGCGCGTTTGAAGGCTGAACTGAAATCTGTGGCAGGGGATGAAAAAATAGTTG ACGAGTCAGCCATGCCAAAGTTGCCTTACTTGCAGGCCGTCATAAAGGAAGTTATGC GTATACACCCTCCGGGGCCGTTGCTTTTGCCTCGTAAAGCTGAAAGCGATCAAGAAG TGAATGGATACCTTATTCCGAAAGGCACACAGATCCTGATAAATGCATATGCGATAG GACGTGATCCATCAATCTGGACTGACCCCGAAACATTTGACCCGGAACGTTTCCTGG ATAACAAGATTGATTTCAAGGGACAAGATTACGAGCTGTTGCCGTTCGGCTCCGGAC GTCGTGTATGTCCGGGGATGCCGTTAGCTACTAGAATACTTCACATGGCAACCGCCA CGCTAGTCCACAACTTCGACTGGAAATTAGAAGACGATAGTACAGCCGCTGCAGAC CACGCAGGCGAGCTATTTGGAGTTGCAGTGAGAAGGGCAGTTCCGCTTCGTATAATC CCGATAGTGAAGTCC >CPR_1 Seq. ID NO: 13 ATGGCCGCAGGAGATTCTCATGTGGATACGTCGTCCACTGTGTCTGAAGCTGTTGCT GAAGAGGTATCTTTATTCAGTATGACTGACATGATCCTATTCAGCCTTATTGTGGGG CTACTGACCTACTGGTTCCTATTCAGAAAGAAGAAGGAAGAGGTCCCAGAGTTCAC CAAGATCCAAACGCTGACTTCCAGCGTCCGTGAATCATCCTTTGTTGAGAAAATGAA GAAAACAGGGCGTAATATCATTGTGTTTTATGGTAGTCAGACTGGCACTGCAGAAG AGTTCGCCAACAGGTTGTCTAAAGATGCGCACAGATATGGTATGAGGGGTATGTCTG CGGACCCGGAGGAATATGACTTAGCGGACTTGTCCTCTCTGCCTGAAATTGATAACG CGCTAGTGGTCTTCTGTATGGCTACGTACGGAGAAGGCGATCCAACCGATAATGCCC AAGACTTCTACGATTGGTTGCAAGAGACTGACGTGGATTTGTCCGGAGTAAAGTTCG CAGTATTTGGGCTGGGAAACAAAACTTATGAACATTTTAATGCAATGGGTAAGTACG TAGACAAACGTTTAGAACAACTGGGTGCACAAAGAATATTCGAGCTTGGTTTGGGG GATGATGACGGTAATTTAGAGGAGGATTTCATCACTTGGAGGGAGCAATTCTGGCC GGCGGTGTGCGAGCATTTCGGCGTTGAGGCGACCGGAGAAGAGTCAAGCATTAGAC AGTATGAACTTGTTGTGCACACAGATATCGACGCCGCAAAAGTGTATATGGGGGAG ATGGGTAGATTAAAATCTTATGAGAATCAAAAACCTCCTTTCGATGCGAAAAATCCA TTCCTTGCCGCTGTGACCACAAACAGGAAACTAAATCAAGGTACAGAGCGTCATTTG ATGCACTTGGAGCTAGACATCAGTGATTCTAAAATTAGGTACGAATCAGGGGATCA CGTCGCCGTTTATCCCGCCAATGATAGCGCCTTGGTGAATCAGTTAGGTAAGATACT GGGTGCTGATTTGGATGTAGTCATGAGCTTGAATAACCTTGATGAAGAGTCCAATAA GAAACATCCTTTCCCGTGCCCAACAAGTTATAGAACCGCCCTTACGTACTACTTAGA TATCACCAATCCACCAAGAACGAATGTCCTATATGAGCTTGCTCAATATGCCAGTGA GCCATCCGAGCAAGAGCTGCTTAGGAAAATGGCGTCCTCATCCGGTGAAGGCAAAG AATTATACCTGTCCTGGGTGGTCGAGGCCAGGAGGCATATTTTAGCTATTTTGCAAG ATTGTCCTTCCCTTAGGCCGCCCATCGATCATCTTTGTGAGCTGCTTCCTCGTTTACA AGCAAGGTATTATTCTATCGCGTCCTCCTCTAAAGTCCATCCAAACAGCGTACACAT CTGTGCCGTGGTGGTCGAGTACGAGACGAAGGCCGGTAGAATCAACAAGGGCGTTG CTACAAACTGGTTGAGAGCCAAGGAGCCCGCGGGGGAAAACGGAGGTCGTGCATTA GTACCGATGTTTGTCCGTAAATCTCAATTCAGGTTGCCTTTTAAGGCAACCACTCCG GTAATCATGGTCGGGCCTGGCACTGGCGTAGCCCCATTTATAGGATTCATTCAGGAA AGGGCCTGGTTGAGGCAACAAGGCAAGGAGGTTGGAGAGACTCTGCTGTACTACGG ATGCCGTAGGAGCGACGAAGATTACTTGTATCGTGAAGAGCTTGCACAATTTCACCG TGACGGAGCACTTACTCAATTAAATGTGGCTTTTAGTCGTGAACAGTCACATAAGGT GTATGTACAACATTTATTGAAGCAAGACCGTGAACACCTTTGGAAGCTGATTGAAGG TGGCGCCCATATTTATGTATGCGGCGATGCTCGTAATATGGCAAGGGACGTTCAAAA CACTTTCTATGACATCGTCGCAGAACTTGGGGCGATGGAGCATGCTCAAGCAGTAGA TTACATCAAGAAACTAATGACCAAAGGTAGATATTCACTTGACGTTTGGTCCTAA >CPR_2 Seq. ID NO: 14 ATGGCCGCACCTTTCGGTATTGACAATACTGACTTCACTGTCTTGGCGGGCCTGGTA CTGGCAGTACTGTTGTATGTGAAGAGGAACAGTATAAAAGAACTGTTGATGTCAGA TGATGGTGACATCACAGCTGTTTCTAGTGGGAACAGAGACATTGCCCAGGTCGTCAC GGAAAATAATAAAAACTATCTAGTCCTGTATGCTTCACAGACCGGCACCGCAGAAG ATTATGCGAAGAAATTTAGCAAGGAGCTGGTAGCCAAGTTCAACCTTAATGTGATGT GCGCTGACGTAGAGAATTACGACTTCGAATCCTTAAACGATGTACCGGTTATCGTTT CTATCTTCATTTCCACCTACGGAGAGGGCGATTTTCCAGACGGTGCGGTTAACTTCG AAGACTTTATATGTAATGCTGAGGCTGGAGCTTTAAGTAACTTACGTTATAATATGT TTGGTCTTGGGAACTCTACTTATGAGTTCTTTAATGGCGCTGCCAAGAAAGCCGAAA AACACTTATCTGCGGCGGGGGCCATCAGACTGGGCAAACTTGGAGAGGCCGACGAT GGTGCCGGGACAACGGACGAGGATTATATGGCTTGGAAGGATTCTATATTGGAGGT TCTAAAGGATGAACTACACTTAGATGAGCAGGAAGCCAAATTTACTTCCCAGTTTCA GTATACTGTTCTGAACGAAATAACAGACTCCATGTCTTTGGGCGAACCGTCTGCGCA TTACCTACCCAGCCATCAACTGAACAGAAACGCGGACGGAATACAGCTAGGGCCCT TTGACTTATCGCAGCCTTACATTGCCCCAATTGTAAAATCTAGGGAGCTGTTTAGTTC TAATGATAGGAATTGCATACATAGCGAGTTCGACTTGTCCGGTTCTAATATTAAGTA CTCTACAGGTGACCACCTGGCCGTATGGCCGAGCAATCCCCTTGAGAAGGTAGAAC AATTTTTGTCAATCTTCAACCTAGATCCAGAAACGATATTCGATTTGAAGCCCCTGG ACCCGACTGTTAAGGTACCGTTTCCCACTCCTACCACCATAGGTGCGGCAATCAAGC ACTATTTGGAAATCACAGGCCCGGTATCACGTCAATTGTTTAGTAGCTTAATTCAAT TCGCCCCGAATGCTGACGTAAAGGAGAAACTAACCCTGCTAAGTAAGGACAAGGAC CAATTCGCTGTGGAAATTACCAGTAAATATTTCAACATAGCGGATGCTTTAAAGTAT CTGAGTGATGGGGCTAAATGGGACACTGTGCCCATGCAATTTCTGGTGGAGTCCGTG CCCCAAATGACCCCCAGGTACTACAGTATCAGTTCATCCAGCCTAAGTGAGAAGCA GACGGTCCATGTAACAAGCATAGTAGAGAATTTCCCAAATCCCGAATTACCGGATG CGCCCCCTGTCGTGGGAGTGACAACCAATCTTCTAAGGAATATCCAACTAGCCCAAA ACAATGTGAATATCGCGGAAACGAACCTACCCGTTCACTACGATCTTAATGGACCCA GGAAACTTTTTGCAAATTACAAACTTCCCGTCCATGTTAGGAGATCAAATTTTAGGC TACCTTCCAATCCAAGCACTCCAGTGATCATGATTGGACCGGGTACTGGAGTTGCGC CTTTCCGTGGGTTCATTAGGGAAAGAGTAGCCTTTTTGGAGAGTCAGAAGAAAGGC GGAAATAATGTCAGCTTGGGCAAACACATATTGTTTTACGGTTCACGTAACACCGAC GACTTCCTTTACCAGGATGAATGGCCAGAGTACGCTAAGAAACTAGACGGGTCTTTT GAGATGGTTGTGGCCCACTCTAGGCTTCCAAACACGAAGAAGGTCTATGTACAGGA TAAGCTGAAAGACTATGAGGATCAAGTTTTTGAAATGATAAACAACGGGGCGTTCA TTTATGTTTGCGGAGACGCAAAAGGGATGGCTAAGGGTGTGAGCACAGCCTTGGTC GGTATCTTATCAAGAGGGAAGTCAATAACTACAGACGAAGCCACTGAGCTAATTAA AATGCTTAAAACGAGCGGAAGGTACCAAGAGGACGTTTGGTAA >CPR_3 Seq. ID NO: 15 ATGGCCGCAGGAGACAGCCACGAAGATACTAGTGCGACCGTTCCGGAGGCAGTGGC GGAAGAGGTGAGCCTATTCAGTACTACCGATATTGTACTTTTCTCCCTAATTGTGGG TGTGCTGACTTACTGGTTCATATTTAAAAAGAAGAAAGAGGAGATTCCCGAATTTTC CAAAATCCAAACGACAGCTCCACCCGTTAAAGAAAGTAGTTTCGTCGAGAAAATGA AGAAGACTGGGAGGAATATAATAGTTTTCTATGGAAGCCAAACAGGGACCGCAGAG GAGTTCGCGAACAGACTAAGTAAAGACGCTCATAGATACGGTATGCGTGGTATGTC CGCTGACCCAGAGGAGTACGACCTGGCAGACCTAAGCTCACTGCCAGAGATTGACA AAAGCCTAGTGGTCTTCTGTATGGCTACATATGGTGAAGGTGATCCAACTGATAACG CTCAGGATTTCTACGATTGGTTACAAGAGACAGATGTGGACCTGACTGGAGTTAAAT TTGCAGTCTTCGGCTTGGGGAATAAAACATACGAACACTTTAATGCTATGGGGAAAT ACGTCGATCAAAGATTGGAGCAACTTGGCGCCCAGAGAATTTTCGAGCTAGGCTTG GGAGACGACGATGGGAATCTTGAGGAGGATTTTATAACTTGGAGAGAACAGTTTTG GCCAGCCGTGTGCGAATTTTTCGGAGTCGAGGCGACAGGCGAAGAGTCAAGTATCA GGCAATATGAGCTAGTTGTGCATGAAGATATGGACACGGCGAAAGTCTACACCGGC GAGATGGGACGTCTAAAAAGTTACGAGAACCAAAAACCGCCTTTTGATGCGAAGAA TCCATTCTTGGCCGCCGTCACGACAAACCGTAAGTTAAACCAAGGGACTGAAAGAC ATCTGATGCACTTAGAGCTTGACATCTCCGATAGTAAAATAAGGTATGAAAGTGGA GATCACGTCGCCGTATACCCGGCTAACGATTCAACTCTAGTTAATCAGATCGGGGAA ATATTAGGGGCCGACCTAGACGTCATAATGAGTTTAAACAACCTAGATGAAGAATC AAACAAGAAACACCCATTCCCCTGTCCAACCACTTACAGGACAGCGTTGACTTATTA TCTTGATATCACCAATCCCCCGAGAACCAACGTGTTATATGAACTTGCTCAGTATGC CAGTGAACCATCTGAGCAGGAACATCTGCACAAGATGGCATCCTCATCAGGAGAAG GAAAAGAATTATATCTGTCCTGGGTCGTGGAGGCTAGGAGACATATCCTTGCGATCC TGCAGGACTATCCTAGCTTGCGTCCGCCTATCGACCATTTATGCGAACTGCTACCTC GTTTGCAGGCCAGGTACTACAGCATAGCCTCTAGTAGTAAAGTACATCCTAACTCTG TGCATATATGTGCCGTGGCCGTGGAGTACGAGGCTAAATCAGGAAGAGTAAATAAA GGAGTCGCAACGAGTTGGCTGAGGACTAAGGAACCAGCCGGCGAGAACGGTAGGA GAGCACTGGTGCCCATGTTTGTGAGGAAGTCCCAATTTCGTCTGCCATTTAAGCCTA CAACCCCGGTAATTATGGTCGGTCCCGGGACAGGTGTAGCTCCGTTCATGGGATTTA TCCAAGAGCGTGCCTGGTTGAGGGAACAGGGTAAAGAAGTCGGAGAGACCTTATTA TACTATGGATGTAGGCGTTCAGACGAGGATTATTTATACCGTGAGGAGTTAGCCCGT TTTCACAAAGACGGGGCCTTAACCCAGCTTAATGTAGCTTTTTCTAGGGAGCAAGCG CATAAGGTCTATGTTCAACACTTGCTTAAAAGGGATAAAGAACACTTGTGGAAGCTA ATACACGAAGGAGGAGCCCATATCTATGTTTGCGGAGATGCCAGGAACATGGCCAA GGACGTACAAAATACCTTTTATGATATTGTCGCAGAATTTGGTCCTATGGAGCACAC ACAAGCTGTAGACTATGTTAAGAAACTAATGACAAAAGGCAGGTACAGTCTGGATG TCTGGTCTTAA >CPR_4 Seq. ID NO: 16 ATGGCCGCAGGTGATTCCCATGAGGACACTTCCGCTACTATGCCGGAGGCCGTAGC GGAGGAGGTCTCATTGTTTTCCACGACTGACATGGTCCTGTTCAGCCTGATCGTCGG CGTTTTGACGTATTGGTTCATATTTAGAAAGAAAAAGGAAGAAATCCCCGAGTTCTC CAAAATCCAAACCACTGCCCCTCCGGTAAAAGAAAGCTCTTTTGTTGAGAAGATGA AGAAGACAGGCCGTAATATCATCGTGTTTTATGGTAGCCAGACTGGTACAGCCGAG GAATTTGCAAACAGACTGAGCAAGGACGCGCACAGGTACGGTATGCGTGGCATGTC CGCCGATCCCGAAGAGTATGATCTAGCCGACCTGAGCAGCTTACCGGAAATCGATA AATCCCTTGTTGTCTTTTGCATGGCGACCTATGGAGAGGGCGATCCGACCGATAACG CACAGGACTTCTATGATTGGTTGCAAGAGACGGACGTAGACCTGACAGGCGTGAAG TTCGCCGTCTTCGGACTGGGCAATAAAACATACGAGCACTTCAACGCAATGGGCAA GTATGTGGATCAGCGTTTAGAGCAACTAGGCGCCCAAAGGATTTTCGAGTTGGGTCT GGGAGACGACGATGGAAACCTAGAAGAAGATTTCATAACCTGGCGTGAGCAATTCT GGCCTGCAGTATGCGAGTTCTTTGGTGTTGAGGCCACGGGCGAAGAATCATCTATAA GGCAGTATGAATTGGTCGTTCACGAAGATATGGACGCCGCGAAGGTATACACCGGC GAAATGGGGCGTCTTAAATCATACGAAAACCAAAAACCTCCCTTTGACGCTAAAAA TCCATTTCTAGCTGCTGTCACCGCAAATCGTAAGTTAAACCAGGGCACTGAGAGGCA CCTAATGCACCTGGAGCTGGATATCAGCGATTCCAAAATCAGATACGAATCAGGAG ACCACGTCGCGGTGTATCCCGCAAACGATTCAGCGTTAGTAAACCAAATCGGGGAA ATACTTGGAGCGGATCTTGATGTGATAATGTCTTTAAATAACCTAGACGAGGAATCC AATAAGAAACACCCATTTCCCTGTCCTACGACATACAGAACCGCGCTGACGTATTAT TTGGATATAACAAATCCTCCCAGAACGAACGTTCTATATGAGTTAGCCCAGTATGCT TCAGAGCCGAGTGAACAGGAACATCTGCACAAGATGGCGAGCAGTTCAGGAGAGG GTAAGGAATTATACCTTTCCTGGGTCGTTGAGGCGCGTAGACACATACTTGCAATTC TACAAGACTACCCTAGCCTAAGACCACCTATAGACCATCTGTGCGAGTTATTGCCAC GTTTGCAAGCCAGGTATTATAGCATCGCAAGTTCTTCTAAAGTTCACCCCAACTCTG TGCACATATGTGCAGTTGCTGTCGAATACGAAGCAAAATCCGGGAGGGTTAATAAG GGAGTAGCTACGAGTTGGCTAAGAGCAAAAGAACCAGCTGGTGAAAATGGAGGTCG TGCCCTTGTCCCGATGTTTGTAAGAAAATCCCAATTCAGACTACCGTTTAAGAGTAC CACGCCCGTGATCATGGTTGGTCCGGGGACTGGTATAGCACCTTTTATGGGGTTCAT CCAGGAGCGTGCCTGGCTACGTGAGCAAGGCAAAGAGGTAGGCGAGACATTGCTTT ACTACGGGTGTAGACGTAGCGATGAAGATTACCTGTACAGAGAAGAGTTGGCGAGA TTCCACAAAGACGGCGCTTTAACCCAACTAAACGTCGCTTTTAGCAGAGAACAGGCT CATAAAGTGTACGTCCAGCACTTGCTGAAAAGGGACAGGGAGCATTTATGGAAACT GATTCATGAAGGTGGCGCGCACATATACGTATGCGGGGATGCTCGTAATATGGCTA AGGATGTGCAGAATACATTTTACGACATTGTAGCGGAGTTCGGCCCTATGGAGCATA CGCAAGCTGTAGATTATGTCAAGAAATTAATGACCAAAGGTAGATACTCATTGGAC GTTTGGAGCTAA >CPR_5 Seq. ID NO: 17 ATGGCCGCAATCAACATGGGTGACTCTCATGTTGACACAAGTTCCACCGTTTCCGAA GCTGTAGCGGAAGAAGTGAGCCTATTCAGCATGACAGATATGATTCTATTCTCACTT ATTGTCGGTTTACTGACTTACTGGTTTCTATTCAGAAAGAAGAAGGAAGAGGTCCCC GAATTTACGAAAATACAAACACTTACTTCCTCAGTTAGGGAATCATCATTCGTTGAG AAAATGAAAAAGACGGGGCGTAACATCATCGTGTTTTATGGTTCACAAACCGGAAC TGCCGAAGAGTTTGCGAATAGATTATCTAAGGACGCTCATAGATACGGAATGCGTG GGATGTCTGCCGATCCCGAGGAATATGATCTGGCAGATCTTAGCAGTCTACCGGAAA TCGACAATGCACTTGTGGTGTTCTGCATGGCAACATACGGGGAAGGAGATCCGACG GATAATGCACAGGACTTTTATGACTGGTTGCAAGAGACCGACGTGGATCTATCCGGT GTCAAGTTTGCCGTTTTTGGGCTTGGGAATAAGACCTACGAGCACTTCAATGCAATG GGAAAATATGTGGATAAGAGACTGGAGCAGCTGGGAGCCCAAAGAATATTCGAGTT AGGATTAGGTGACGATGATGGGAATCTTGAGGAAGACTTCATCACCTGGCGTGAAC AGTTTTGGCCGGCAGTTTGCGAACACTTTGGTGTAGAAGCCACTGGGGAAGAGTCTT CCATCAGGCAATACGAGCTGGTAGTGCATACAGATATTGATGCAGCTAAGGTATAT ATGGGTGAGATGGGAAGGTTAAAAAGTTATGAGAACCAGAAACCACCTTTTGATGC CAAAAATCCTTTTCTGGCCGCAGTTACGACAAACAGGAAATTAAACCAGGGTACGG AAAGACACTTAATGCATTTAGAACTGGACATCTCAGACAGCAAGATTAGGTACGAA AGTGGGGACCACGTCGCAGTGTACCCGGCTAATGACAGCGCGCTAGTGAATCAGCT GGGTAAAATTCTAGGGGCGGATCTTGACATCGTGATGAGCCTGAATAATTTGGACG AAGAGAGCAACAAGAAACATCCCTTCCCCTGTCCTACTTCCTATAGGACGGCTCTAA CATATTATCTGGACATAACGAATCCCCCTAGAACGAACGTCTTGTACGAATTGGCAC AGTACGCTTCTGAACCGTCAGAACAGGAATTACTACGTAAAATGGCGAGTTCTAGTG GTGAAGGAAAAGAGTTATACCTAAGTTGGGTTGTAGAGGCAAGGAGACACATTCTG GCTATTTTACAAGATTGCCCTAGTTTGAGGCCGCCTATAGACCACCTTTGTGAGTTAT TACCGAGGTTACAGGCTCGTTACTATTCTATAGCAAGCAGTAGTAAGGTCCACCCGA ATAGCGTACACATATGCGCCGTAGTAGTAGAATACGAAACAAAGGCGGGTCGTATC AACAAAGGAGTGGCGACCAACTGGTTGCGTGCCAAAGAACCGGCAGGAGAAAACG GTGGGAGGGCTCTAGTTCCGATGTTTGTCCGTAAAAGTCAGTTTAGGTTACCGTTCA AGGCCACGACCCCCGTAATCATGGTAGGTCCCGGGACTGGAGTTGCGCCGTTCATA GGCTTTATCCAGGAAAGGGCCTGGTTGCGTCAGCAGGGCAAGGAGGTCGGTGAAAC ACTGTTATACTATGGATGCAGGAGGAGTGACGAGGACTATCTGTACAGAGAAGAGC TTGCCCAATTCCACAGGGACGGCGCATTGACTCAACTTAACGTAGCCTTCTCACGTG AACAGTCTCACAAGGTGTACGTCCAACACCTGCTGAAGAGAGACAGGGAGCATCTG TGGAAATTAATAGAAGGCGGAGCACATATCTATGTATGTGGCGATGCAAGAAACAT GGCACGTGATGTCCAGAATACCTTTTACGATATTGTCGCGGAGCTTGGGGCGATGGA ACACGCTCAAGCCGTAGATTACATCAAGAAACTAATGACAAAGGGGCGTTATTCTCT TGACGTATGGTCCTAA >CPR_6 Seq. ID NO: 18 ATGGCCGCAATTAACATGGGAGATTCCCACATGGATACATCCAGCACAGTGTCCGA AGCAGTTGCGGAGGAAGTGAGTTTATTTTCCATGACAGACATGATCCTTTTCTCACT TATTGTGGGGTTACTTACCTACTGGTTTTTGTTTAGGAAAAAGAAAGAGGAGGTCCC GGAATTTACTAAAATACAGACTTTGACATCATCAGTACGTGAGTCTTCCTTTGTAGA GAAAATGAAGAAGACAGGCAGGAATATAATAGTATTTTATGGATCTCAGACCGGGA CCGCAGAGGAGTTCGCTAACCGTCTATCCAAAGACGCCCACCGTTATGGTATGAGG GGCATGAGTGCGGACCCCGAGGAGTACGATCTAGCCGATCTATCCAGCTTACCTGA GATAGAGAACGCATTGGTTGTATTTTGTATGGCCACGTATGGCGAAGGTGATCCGAC AGATAATGCTCAAGATTTCTACGACTGGTTACAAGAGACCGACGTAGACTTGTCTGG TGTAAAGTTCGCTGTATTTGGATTAGGAAATAAGACCTATGAACACTTTAACGCCAT GGGCAAGTATGTCGATAAACGTCTGGAACAATTAGGCGCTCAGAGAATTTTCGAAC TGGGACTAGGCGATGACGACGGAAACCTGGAGGAGGACTTTATTACGTGGAGAGAA CAATTTTGGCCCGCTGTCTGTGAACATTTCGGCGTTGAGGCAACCGGCGAAGAAAGC TCGATAAGGCAATATGAATTGGTAGTACATACAGATATAGACGCCGCTAAAGTGTA CATGGGAGAAATGGGAAGGTTGAAGAGTTATGAGAACCAAAAACCTCCGTTCGACG CTAAGAATCCGTTCCTAGCGGCTGTCACTACAAATAGAAAGTTGAATCAAGGCACA GAAAGGCATTTAATGCATTTAGAGCTTGATATTTCTGACAGCAAAATCAGATACGAA TCCGGGGACCATGTTGCGGTCTACCCAGCAAACGACAGTGCCTTAGTAAATCAGCTA GGGAAAATACTTGGGGCGGATTTGGATGTCGTAATGAGTCTTAATAACCTAGATGA AGAATCAAATAAGAAACATCCATTTCCTTGTCCCACAAGCTATAGGACCGCGCTGAC TTACTATCTGGACATCACTAATCCCCCAAGAACCAATGTGTTGTATGAGTTAGCCCA GTATGCCAGCGAGACGAGTGAGCAAGAGTTATTGAGAAAAATGGCAAGTAGCTCAG GAGAAGGGAAGGAGCTGTATCTGAGCTGGGTTGTAGAGGCACGTAGACACATTCTG GCCATTTTGCAAGATTGCCCTTCTTTGAGACCACCTATAGATCATCTTTGTGAGCTTC TACCAAGGCTGCAGGCTCGTTACTACAGTATTGCTAGTTCAAGCAAAGTTCATCCAA ACAGTGTCCACATCTGCGCGGTCGTAGTTGAATACGAGACAAAGGCCGGGAGAATT AATAAAGGTGTGGCCACTAATTGGCTAAGAGCCAAAGAACCTGCTGGTGAGAACGG TGGGCGGGCGCTTGTCCCGATGTTTGTAAGGAAGAGTCAATTTCGTCTGCCATTTAA GGCGACCACGCCTGTTATTATGGTGGGTCCAGGAACAGGTGTAGCCCCATTTATAGG ATTCATTCAAGAAAGGGCCTGGTTAAGGCAACAAGGCAAAGAGGTTGGTGAAACTC TTCTTTATTATGGGTGTCGTAGATCAGATGAAGATTACCTGTATCGTGAAGAGCTTG TACAATTCCATAGAGACGGCGCGCTTACACAATTGAATGTTGCTTTTAGTCGTGAGC AAAGTCATAAAGTCTACGTTCAACATTTATTAAAAAGGGATAGAGAGCACTTGTGG AAACTGATAGAAGGAGGGGCGCATATCTATGTATGCGGAGACGCGAGGAATATGGC TAGAGACGTGCAAAATACCTTTTATGATATCGTTGCAGAATTGGGTGCAATGGAGCA TACGCAAGCCGTTGATTACATAAAGAAGTTGATGACCAAAGGACGTTACAGCCTAG ATGTTTGGTCTTAA >CPR_7 Seq. ID NO: 19 ATGGCCGCAAATATGGCAGACAGTAATATGGATGCGGGAACGACCACATCTGAGAT GGTAGCAGAGGAGGTAAGCCTATTTTCCACTACGGATGTGATATTGTTCAGTTTGAT CGTAGGTGTTATGACTTATTGGTTTCTTTTCAGGAAAAAGAAAGAAGAGGTGCCGGA GTTCACAAAGATTCAGACCACTACCTCCTCCGTTAAGGATAGATCATTTGTTGAAAA GATGAAGAAAACCGGCAGGAATATCATTGTGTTCTACGGTAGCCAGACAGGAACGG CGGAAGAGTTCGCCAACCGTCTATCCAAAGACGCTCACAGATATGGTATGAGGGGA ATGGCGGCCGACCCGGAGGAGTACGACCTGGCTGATCTGTCTTCTTTGCCAGAAATA GAGAAGGCGTTGGCTATATTCTGTATGGCAACCTATGGAGAAGGGGACCCAACAGA TAACGCTCAGGACTTTTACGATTGGTTGCAAGAGACTGATGTGGACCTAAGTGGTGT AAAGTATGCGGTATTTGCCCTGGGGAACAAGACGTACGAGCACTTCAATGCAATGG GTAAGTACGTAGATAAGAGACTGGAACAGTTGGGAGCGCAAAGGATATTCGACTTG GGATTAGGTGATGACGACGGAAACCTAGAGGAAGATTTCATAACCTGGAGGGAACA ATTCTGGCCCGCCGTTTGTGAGCATTTTGGCGTTGAAGCAACGGGTGAAGAGAGTTC TATCCGTCAATACGAGTTGATGGTACATACGGATATGGATATGGCAAAAGTTTACAC CGGTGAAATGGGAAGACTAAAGTCATACGAAAACCAGAAGCCCCCATTTGATGCGA AAAACCCTTTCCTAGCAGTCGTAACGACGAACCGTAAGCTGAATCAGGGGACGGAG AGGCACTTAATGCACTTAGAACTTGATATATCTGACTCTAAAATTAGATATGAATCT GGGGACCATGTAGCCGTATATCCAGCAAACGATAGCGCCTTAGTAAACCAACTGGG CGAGATATTGGGGGCTGATCTGGATATCATAATGAGTTTGAACAACTTGGATGAAG AAAGTAACAAGAAACATCCGTTCCCTTGTCCCACATCATATAGAACAGCCCTTACCT ACTACTTGGACATAACAAACCCGCCAAGAACTAACGTTCTATACGAGTTGGCTCAAT ATGCGAGCGAACCGACCGAACATGAACAACTACGTAAAATGGCATCTTCATCTGGT GAGGGTAAGGAACTTTACTTGAGGTGGGTGCTTGAAGCTAGAAGGCATATCCTGGC GATTTTGCAAGACTATCCTAGTCTAAGACCGCCGATTGATCACTTGTGTGAGCTTCTT CCTAGACTTCAAGCTAGGTACTACTCAATCGCCAGCAGTTCAAAAGTGCACCCGAAC TCAGTACATATATGTGCCGTAGCCGTCGAGTACGAGACCAAGACGGGCAGGATAAA CAAAGGAGTCGCCACAAGTTGGCTGAGAGCTAAGGAACCAGCAGGCGAAAATGGT GGGCGTGCCCTAGTGCCTATGTATGTGCGTAAAAGTCAGTTCAGATTACCGTTCAAA GCTACGACCCCTGTAATAATGGTAGGCCCGGGCACTGGAGTGGCCCCCTTCATTGGA TTCATTCAAGAGCGTGCCTGGCTAAGGCAACAGGGGAAGGAGGTTGGGGAAACATT GTTGTATTATGGGTGCAGGAGAAGCGACGAGGATTATCTATATAGGGAAGAGCTGG CGGGCTTCCATAAGGACGGCGCGCTGACTCAATTAAATGTTGCATTCAGCAGGGAA CAACCCCAAAAGGTGTACGTGCAGCACTTACTTAAAAAGGATAAGGAACACTTATG GAAATTAATTCACGAGGGTGGAGCCCACATCTACGTGTGTGGGGATGCCAGGAATA TGGCTAGGGATGTCCAGAACACATTCTATGATATTGTAGCCGAACAAGGTGCGATG GAGCACGCCCAAGCTGTTGACTATGTCAAGAAATTGATGACCAAAGGGAGATACTC TCTGGACGTCTGGTCATAA >CPR_8 Seq. ID NO: 20 ATGGCCGCTGAACCTACCTCACAAAAGCTTAGTCCTCTTGACTTCATTGCGGCCATT CTAAAAGGTGATTATTCAGATGGGCAACTGGAAGCTGCATCCCCGGGGATGGCTAT GCTGCTGGAGAATAGAGATCTTGTAATGGTTCTTACAACAAGTGTGGCTGTATTGAT AGGGTGTGTGGTGGTGTTAGCCTGGAGACGTACGGCCGGTTCAGCCACCAAAAAGC AGTTTGAGCCTCCCAAGCTTGTAGTACCGAAAGCCGCAGAACTGGAGGAAGTTGAT GACGACAAACCTAAGGTAAGTATCTTCTTTGGTACCCAAACCGGAACCGCGGAGGG CTTTGCGAAAGCTTTCGCCGAGGAGGCCAAGGCCAGATATCCCCAGGCTAACTTCA AGGTGATCGACTTAGATGATTACGCAGCAGACGACGACGAGTATGAGGAGAAACTG AAGAAGGAGACGCTGGCGTTCTTCTTTCTGGCGTCCTACGGCGATGGAGAGCCCACA GACAACGCGGCTAGATTCTACAAGTGGTTCACTGAGGGGAAGGATAGAGGTGATTG GTTGAAAAATTTACAATACGGAGTGTTTGGTCTAGGCAATAGACAATATGAGCACTT TAATAAAATCGCTATCGTTGTGAATGACATCATTGTCGAGCAAGGTGGAAAAAAGC TAGTGTCAGTGGGCCTTGGGGACGACGATCAGTGCATAGAAGACGACTTCGCCGCTT GGAGAGAATTAGTATGGCCAGAACTTGACAAGTTGCTTCGTAACGAAGACGATGCC ACCGTCTCTACACCATACACCGCAGCAGTACTGCAATATAGGGTTGTCTTTCATGAT CAGACAGACGGCTTAATCTCCGAGAACGGCTTCTTGAACGGCAGAGCGAACGGGAC GTCTGTCTTCGATGCCCAACACCCCTGTCGTTCCAACGTCGCGGTCAAAAAAGAACT TCACACCCCCGCTAGTGACCGTAGTTGTGCCCATCTTGAATTTGATATATCTGGGACT GGGTTAGTCTATGAAACTGGAGATCATGTTGGAGTTTACTGCGAAAACCTAATTGAA ACTGTAGAGGAGGCCGAAAAGTTGTTAAATATTCCCCCTCAAACATATTTTTCCATA CATACGGATAATGAGGATGGGTCCCCTCGTAGCGGCAGCTCTCTTCCGCCTCCATTC CCGCCATGCACTTTAAGAACGGCCTTGACCAGGTATGCGGATTTGTTGTCCGCGCCT AAAAAAAGCACCTTAATTGCTCTAGCAGAGAGTGCCAGCGATCAGAGTGAAGCCGA CAGATTACGTCACCTTGCGAGCCCCGGTGGTAAGGAGGAATACGCTCAATATATCAC CGCAAGCCAAAGGTCCCTGCTAGAGGTAATGGCGGACTTCCCCAGTGCGAAGCCTT CATTGGGCGTCTTTTTCGCAGCCATAGCCCCCCGTTTGCAGCCCCGTTTTTACTCTAT CTCAAGCTCACCGAAAATAGCACCTAGCAGGATACATGTTACGTGCGCGCTGGTTTA TGAAAAAACGCCTACGGGTCGTGTTCATAAGGGTGTCTGCAGTACATGGATGAAGA ACGCTGTGCCCCTGGAGGAATCTAATGACTGTAGCTGGGCGCCGATATTTGTCAGGA ACTCCAACTTCAAGCTACCTGCCTATCCCAAAGTGCCCATAATTATGATTGGCCCTG GAACTGGTCTGGCCCCGTTCAGAGGTTTTCTACAAGAGCGTCTTGCGTTAAAAGAAT CAGGTGCCGAATTGGGACCAGCTATACTATTCTTCGGGTGTAGGAATAGAAAAATG GACTTCATCTATGAAGATGAGCTAAACAACTTCGTAGAGGCGGGCGTTATAAGTGA ACTGATAGTAGCGTTTAGTAGGGAGGGACCAACTAAGGAGTATGTACAACACAAGA TGACTCAGAGGGCGTCAGATGTATGGAAGATCATAAGCGATGGAGGTTATGTTTAT GTGTGCGGCGACGCGAAAGGAATGGCAAGGGATGTTCACCGTACACTACATACAAT AGCACAAGAGCAGGGCAGCCTTTCTTCATCTGAAGCAGAGGGAATGGTGAAAAATC TACAGACAACCGGGCGTTATCTGAGGGACGTATGG >CBNsyn_1 Seq. ID NO: 21 ATGGCCGCAGACTTCTCAGGTAAAAACGTTTGGGTCACGGGGGCCGGTAAAGGTAT AGGTTACGCGACAGCATTGGCATTCGTAGAGGCAGGGGCCAAGGTCACAGGCTTCG ATCAGGCATTTACACAGGAACAGTACCCTTTTGCCACCGAGGTTATGGATGTAGCGG ACGCCGCCCAAGTAGCACAAGTCTGTCAGCGTCTACTAGCTGAGACAGAGAGATTG GATGCTCTGGTGAATGCGGCAGGTATTCTTCGTATGGGTGCCACCGACCAATTATCT AAGGAGGACTGGCAACAAACGTTCGCTGTAAATGTTGGAGGTGCATTTAACCTGTTC CAACAGACTATGAATCAGTTCAGAAGGCAGCGTGGAGGCGCTATAGTCACAGTAGC CAGTGACGCCGCGCATACCCCAAGGATTGGAATGTCAGCGTACGGAGCTTCCAAGG CAGCCCTGAAGAGCCTAGCTTTATCAGTCGGTCTGGAGCTGGCCGGGTCAGGGGTA AGGTGCAACGTTGTGTCCCCGGGCTCCACGGATACAGACATGCAGAGAACTCTGTG GGTGTCTGACGACGCAGAGGAACAACGGATCAGAGGTTTCGGAGAGCAGTTCAAAC TAGGGATTCCGCTGGGCAAGATCGCTAGACCACAAGAGATAGCTAATACTATACTTT TCCTAGCATCCGATTTAGCCAGTCACATCACTTTACAAGACATCGTAGTGGATGGTG GTTCAACACTAGGCGCTTAA >CBNsyn_2 Seq. ID NO: 22 ATGGCCGCAAGCGATCTGCATAATGAGTCCATTTTCATTACAGGCGGAGGCTCTGGT CTTGGGCTGGCCTTAGTGGAAAGGTTTATAGAGGAAGGGGCACAGGTTGCTACACTT GAGCTTAGCGCAGCAAAAGTCGCGTCTCTACGTCAACGTTTTGGAGAACATATATTG GCCGTGGAAGGCAACGTCACGTGTTATGCCGACTATCAAAGAGCTGTAGATCAGAT ACTAACCCGTTCTGGGAAGTTAGATTGCTTTATAGGGAATGCAGGTATATGGGATCA TAACGCTTCCCTGGTTAATACCCCAGCAGAAACGCTAGAAACAGGGTTTCATGAGCT TTTTAACGTAAACGTCCTGGGGTACTTACTGGGAGCAAAAGCATGTGCTCCTGCGCT TATCGCGTCAGAGGGTTCAATGATATTTACCCTTTCAAACGCGGCTTGGTACCCAGG TGGAGGGGGTCCTTTATATACGGCCTCCAAACATGCAGCAACTGGCCTGATCCGTCA ACTAGCCTATGAACTTGCACCCAAGGTAAGGGTTAATGGAGTGGGTCCCTGCGGCAT GGCTAGTGATCTTAGGGGACCACAAGCCTTAGGGCAATCAGAAACGAGTATAATGC AGTCATTGACCCCCGAAAAGATTGCGGCGATATTACCTCTGCAATTTTTCCCACAAC CGGCGGACTTCACTGGACCATACGTCATGTTAACATCTAGGCGTAATAATAGGGCAC TGAGCGGCGTTATGATTAACGCGGACGCTGGGTTGGCTATCAGAGGCATTAGGCAC GTGGCAGCAGGACTTGACCTATAA >CBNsyn_3 Seq. ID NO: 23 ATGGCCGCAACGGGATGGTTAGCGGGAAAAAGAGCTTTGATCGTCGGTGCGGGTTC CGGAATCGGAAGAGCTACAGTTGACGCATTTCTAAACGAGGACGCGAGAGTTGCAG TTCTGGAGTATGACTCCGATAAGTGTGCAACACTTAGGCACCAGTTACCAGACGTTC CCGTGATAGAAGGCGATGGGACCACAAGGACCGCTAACGATGAGGCCGTTCAGGTC GCTGTGGACGCATTCGGGGGACTAGATACTCTGGTCAACTGTGTTGGAATATTCGAC TTCTACCGTCGTATCCAAGACATTCCCGCAGAGCTGATCGATCAGGCATTTGACGAA ATGTTTAGAATCAATGTATTATCACATATCCACTCTGTTAAAGCAGCGGTACCTGCT CTGATGGGTCAGGACGGAGCATCTATTGTGCTGACGGAGAGTGCTTCTTCATTCTAT CCCGGTAGGGGCGGGTTGTTGTATGTGGCGTCAAAATTTGCTGTTCGTGGTGTCGTA ACCGCACTGGCCCATGAGTTGGCTCCCAGGATTCGTGTTAATGGAGTAGCTCCTGGC GGAACCCTTAATACAGATCTGAGGGGCCTTGACAGTTTGGACCTTGGTGCCCGTAGG TTAGATGCCGCGCCTGACAGAGCTAGAGAACTTGCAGCGAGGACCCCACTGGGGGT CGCATTGTCCGGTGAAGACCACGCCTGGTCTTACGTTTTCCTGGCCTCTCATAGGAG TAGAGGTCTAACAGGCGAAACGATTCACCCTGATGGCGGCTTTTCTTTAGGACCGCC GCCACAAAGGAATTAA >CBNsyn_4 Seq. ID NO: 24 ATGAGTAGTATCGAGACCAAAATCTTTCCTGGGCGTTTTGATGGTAGGTGTCTTACC ATAACAGGTGCCGCCCAAGGCATTGGGTTGACAGTAGCTACGAGGATAGCGGCAGA AGGCGGTGAAGTGGTGCTTGTTGACCGTGCAGACCTTGTACACGAGGTGGCAGAGC AGCTACGTGAGGCAGGAGGCAAGGCGCACTCAGTAACGGCTGATTTAGAAACATTT GAGGGTGCTGAGGAAGCGATCTCTCATGCCGTAAGGACGACTGGCAGAATCGATGT ACTAATCAATGTTGTGGGCGGGACTATATGGGCAAAACCGTATGAGCACTACGCCC CGGAGGAAATAGAAAAAGAAATTAGAAGATCCTTATTCCCTACGCTATGGACATGT AGAGCTGCGGCACCGCATTTAATCGAACGTAGAGCAGGAACGATAGTGAACGTAAG CTCCGTTGCTACGAGGGGCGTAAATCGTGTTCCCTATTCCGCAGCAAAGGGAGGTGT TAATGCTATTACTGCGTCTCTGGCGTTGGAATTAGCCCCGTACGGGGTAAGGGTTGT CGCAACGGCTCCAGGCGGGACCGTCGCGCCAGAGAGAAGAATCGCCAGAGGGCCT AGCCCACAGAGTGAGCAGGAGAAAGCCTGGTACCAGCAGATTGTAGATCAGACAGT TGACTCCTCATTACTTAAAAGGTATGGTACTCTTGATGAACAAGCAGCCGCGATCTG CTTCCTTGCATCAGAAGAGGCGTCATACATCACCGGAACTGTCTTGCCGGTGGCCGG AGGGGACTTAGGATAA >CBNsyn_5 Seq. ID NO: 25 ATGAGTAGTACCGGCTGGCTAGACGGCAAAAGGGCCTTAGTTGTTGGGGGAGGAAG TGGGATAGGTAGAGCTGTCGTAGACGCTTTCTTAGCTGAAGGAGCTTGCGTAGCCGT CCTGGAAAGGGACCCGAATAAGTGTAGAGTCCTAAGAGAACATCTGCCGCAGGTGC CCGTAATTGAAGGAGATGCAACAAGGGCTGCAGATAATGACGCAGCGGTAGCTGCA GCAGTTGCTGCATTTGGAGGACTAGACACGCTTGTAAATTGTGTGGGTATCTTTGAC TTCTATCAGGGCATCGAGGACATTCCGGCGGACACCCTTGACGTAGCATTCGATGAA ATGTTCAGAACGAACGTACTATCCCACATGCATAGTGTAAAGGCGGCAGTTCCCGA GTTACGTAAACATAGGGGCTCTTCTATCGTTCTGGCTGAATCCGCCTCTAGCTTCTAT CCAGGGAGAGGGGGTGTCCTATATGTCTCTTCTAAATTTGCCGTCAGAGGTCTGGTA ACCACTCTAGCATACGAGTTGGCCCCAGATATCAGGGTGAATGGGGTCGCCCCAGG TGGTACGCTGAATACGGATCTGCGTGGCTTAGCGTCACTAGGAAGGGATGCTGACA GGCTAGATGATAACCCTAATAGGGCCAATGAGTTAGCAGCCAGAACTCCGCTTAAC GTGGCCCTTAGTGGGGAAGATCATGCGTGGTCTTTTGTCTTCTTCGCTTCCGACAGA AGCAGGGGAATTACAGCCGGGGCTACTCATCCAGATGGAGGCTTTGGAATTGGTGC GCCCAAGCCCTCTACTAGATAA >CBNsyn_6 Seq. ID NO: 26 ATGAGTAGTGGGTTTCTGGATGGCAAGGTTGCTCTTGTGACTGGTGGCGGGAGTGGT ATTGGAAGGGCCGTCGTCGAATTATACGTTCAGCAAGGAGCTAAAGTAGGTATCTTA GAAATCTCACCCGAAAAAGTGAAGGACCTGAGGAATGCCCTACCAGCTGACAGTGT CGTGGTAACAGAGGGAGATGCTACGAGTATGGCGGATAACGAGAGGGCAGTCGCG GACGTTGTTGACGCATTCGGACCCCTTACTACGTTAGTTTGTGTGGTGGGGGTATTC GATTACTTTACAGAGATTCCTCAGCTACCTAAAGATAAAATCTCTGAAGCCTTTGAT CAACTTTTTGGGGTAAATGTTAAATCCAACCTATTGTCTGTGAAAGCGGCGTTAGAC GAGCTAATTGAGAACGAAGGAGACATAATACTGACGCTAAGTAACGCAGCTTTTTA TGCCGGTGGAGGCGGCCCACTGTATGTTTCTAGTAAGTTTGCTGTAAGGGGCTTGGT GACTGAGTTAGCATATGAGCTTGCCCCAAAAGTACGTGTCAACGGGGTAGCCCCAG GGGGAACGATTACCGAACTTAGAGGAATCCCGGCCTTGGCGAATGAAGGACAAAGG CTGAAAGACGTTCCTGACATCGAGGGATTAATAGAAGGAATTAATCCCCTTGGTATC GTTGCTCAGCCTGAGGACCACTCCTGGGCCTACGCGTTATTAGCAAGTAGAGAAAG GACATCAGCGGTAACAGGCACGATTATAAACAGCGATGGAGGATTAGGAGTCAGGG GCATGACTCGTATGGCCGGTCTGGCACAATAA >CBNsyn_7 Seq. ID NO: 27 ATGAGTAGTAGTAGGTCTGTGACTTTGGTAGTCGGCGCTGCCCAAGGAATTGGCAGG GCTACCGCATTGACGCTTGCGACGGCGGGTCACAGGGTCGTGTTGGCGGATAGGGA CGTAGACGGCTTGGCCGAGACTGCTGCGCTTCTACACGTCGCTGCACCGGTTCACGG ACTTGACGTATGTGATGCTGCTGGGGTGGCGGAAGCGGTTGCGAGGGTGGAGGTCG AGCACGGACCGGTAGATGCTCTAGCTCATGTCGCGGGGGTGTTTACCACGGGCTCTG TACTTGATTCAGACTTAGCAGAGTGGCAACGTATGTTTGACGTCAACGTGACGGGGC TAATCAATGTACTGCGTGTCGTGGGGCATGGCATGAGAGAACGTAGACGTGGAGCA ATCGTCACTGTCGGTTCTAATTCCGCTGGTGTACCAAGGGTGGGGATGGGAGCTTAT GGTGCATCAAAATCCGCAGCACATATGCTGGTACGTGTATTAGGATTGGAATTAGCA AGATTCGGCGTCAGGGCGAATGTTGTTGCCCCAGGGTCCACGGACACAGCGATGCA ACGTTCTCTTTGGCCCGACCCTGCTGACGACGCTGGCGCCCGTACTGCGATAGACGG TGACGCCGCTTCATTTAAGGTCGGGATTCCACTGGGGAGGATCGCAGACCCAGCCG ACATCGCGGACGCCGTCGAGTTCCTGCTATCTGATCGTGCTAGGCACATAACAATGC AGACTCTATATGTAGATGGTGGTGCTACCCTGAGAGCATAA >CBNsyn_8 Seq. ID NO: 28 ATGAGTAGTCAAATGCTGGATGACCACGTAGCTCTGATACTAGGTGGTGGGAGTGG ATTGGGTCTAGGAATTGCGCGTCATTTTCTCGGAGAAGGGGCTCAGGTGGCCATCTT TGAGATCAGTGAATCCAAATTATTAGACCTAAAAGCTGAGTTCGGGGACGACGTAC TTCTTTTACAGGGGGATGTAACATCAATTGACGACCTAGAGGCAGCCCGTGCCGCAG TAGTGGATAGGTTCGGAAGGTTGGATGCACTTATTGGTGCGCAAGGGATTTTTGATG GGAACATCCCATTGAGAGACATCCCGACCGAGAGAATCGAAAAGGTTTTCGACGAA GTGCTACATGTTGACGTGCTAGGTTATATATTAGCCGCTAGGGTCTTCCTGGAAGAG CTGGAGAAGACAGACGGAGCAATTGTGTTTACCAGCAGTACTGCGGCTTACGCAGC CGATGGAGGAGGTTTGTTTTACACTGCCGCCAAGGGTGCCGTTAGAAGTGTAATCAA TCAGCTTGCATTCGAGTTCGCGCCGAAGGTCAGAGTCAACGGAGTCGCTCCATCCGG CATCGCTAATTCACAGCTTCAAGGGCCGCGTGCCCTAGGATTAGAGAACAACAAGC AGAGTGATATTCCCGTTGAGGATTTTACGAACCAATTTCTGTCTCTGACGTTGACAC CTACCCTGCCCACTCCGGAGGAATATGCGCCACTTTATGCATATTTAGCGTCCAGGA ACAATACCACAATGACAGGGCAAACGATAATTGCAGATCAGGGCCTATTTAACAGA GCGGTCATATCTAACGGCGTTGCAGATAGAGTAGGCAAATAA >THCdeg_1 Seq. ID NO: 29 ATGAGTAGTTCTGGCCCCGCGCACAGCAATTTAGAGCAAGTATTCGCTAACGTGGCT TCAAATTACCGTGGGGCTGATGTAGACTTGCACGCGGTTTATAGAGAAATGCGTGAG AAGTCTCCCGTGTTGCCTGAAAATTTCATGGCCAGGCTTGGTGTGCCGTCTATAGCA GGGCTGGACCCAAATAGGCCAACTTTTACGTTGTTTAAATATGACGATGTGATGGCT GTAATGAGAGATGCGACTAATTTCACTAGTGGTTTTATTGCGGAAGGTCTGGGCTCT TTCTTCGATGGTTTAATTCTAACAGCAATGGACGGTGAAGCACACAAGAATATACGT TCATTGTTACAGCCGGTCTTTATGCCAGAAACTGTTAATAGGTGGAAAGAGACCAAA ATTGACAGAGTGATAAGGGAAGAGTATCTTAGACCAATGGTGGCTTCAAAGCGTGC CGATATCATGGAGTTTGCTTTATATTTCCCCATTAGAGTTATTTACTCATTGATTGGA TTCCCAGAGGACCGTCCGGAGGAGATCGAACAGTATGCGGCTTGGGCCTTAGCGAT TCTGGCCGGACCTCAAGTAGATCCTGAAAAAGCAGCAGCGGCACGTGGAGCAGCAA TGGAAGCCGCCCAAGCACTGTACGACGTTGTTAAGGTAGTCGTAGCGCAAAGGAGG GCCGAAGGGGCGACAGGCGACGACCTGATTTGCAGACTGATCAGAGCAGAGTACGA AGGACGTAGTCTGGATGACCATGAAATAACGACGTTTGTTAGAAGCCTTCTGCCAGC AGCTTCTGAAACGACGACGCGTACGTTTGGTACATTGATGACTCTGTTGCTAGAACG TCCTGAACTGTTGGCACGTATCCGTGAGGATCGTTCTTTAGTCGGAAAAGCTATTGA TGAGGCGGTACGTTATGAACCAGTGGCTACTTTTAAGGTAAGGCAAGCCGCAAAAG ACGTGGAAATTAGAGGGGTGGCAATTCCGAAGGGCGCGATGGTGTCCTGCATCGTG ACTAGCGCAAATCGTGACGAGGACGCTTTTGAGAATGCGGATACATTCGATATCGA CCGTAGGGCTAAGCCGTCATTTGGATTTGGATTCGGTCCACATATGTGTATTGGTCA GTTTGTTGCTAAAACCGAAATAAACTGCGCCCTAAATGCCATACTGGATTTGATGCC AAACATCCGTTTAGACCCAGATAAACCCGCGCCAGAGATTATAGGGGCGCAGCTAA GAGGACCCCATCACGTCCACGTGATTTGGGACTAA >THCdeg_2 Seq. ID NO: 30 ATGAGTAGTAGGTCAACTGACCTTCCGGACCTGAAATCTGCGGCCTTTCTTGCGGAC CGTTACCCAACGTACAGGAGACTACAAAGTGATTTCCCGCACTTCGAAATGAATATA AATGGAGAGGAGTGTATCGTGCTGACAAGATACAGCGACGTCGATGAAGTCTTACG AAACCCGTTGGCCACGGTTCAACAAGCTCCTGGTGTATTTCCAGAAAGGATAGGTCA AGGTGCTGGGGCCCGTTTCTATCGTGAGTCACTACCCAATATTGATGCCCCCGATCA CACGCGTATCAGGCGTATAGTTACACCGGCGTTCAACCCGAAAACAGTTGCTAACAT GAGAGGTTGGGTTGAGAAGGTAATAGTGGAGCACCTAGACCGTCTTGAAGGATTGG ACGAAATTGACTTTGTCTCTAGCTTTGCCGACCCGGTGCCAGCGGAAATAGCATGTA GGTTGCTTCATGTGCCTGTGTCTGATGCTCCAGAACTTTTTGCTAGGCAGCATGGATT GAATGCTGTGCTATCTGTTAGCGACATCACACCTGAGAGATTAGCCGAAGCGGACG CATCCGCTGCTTTCTACTATGAATACATGGACGACGTTTTAAACACACTGAAGGGTA AATTGCCGGAAGATGATTTCGTGGGAGCGTTAATGGCTGCCGAGGCGCGTGACTCTG GATTAACTAGGTCTGAATTGGTTACTACGCTTATCGGATTTCTGGTAGCCTCATATCA CACCACGAAGGTGGCCATGACAAACACTGTCCTAGCTCTACTTAATCACGATGGCG AGAGAGCTAGGCTTGTGGCGCAGCCGGATTTGGCGAGAAATGCCTGGGAAGAATCA TTGAGATATGACTCCCCAGTGCATTTCGTCCACCGTTATGCATCTGAACCACTGACA ATAGGTGGTCAGCCCGTGGCCCAAGGTAAAAGGCTATTATTGGGCTTGCATGCAGCT AGTAGAGACGAAAATAGGTTTGCCCAGGCAGATCACTACTTGATTGACAGACCGGA TAACCGTCACCTGGCGTTTGCTGGGGGAGGGCACTTTTGCTTGGGGTCTCAACTTAG CCGTTTGGAAGGAGACGTACTGTTGCGTACAATTTTTCAAAGATTCCCCGCAATGAG GCTTACGGAAACCAGATTCGAAAGAGTACCGGACTTGACTTTTCCAATGTTACTAAG GATGACAGTTTCATTAAGGGCGGAGCAAGGTTAA >THCdeg_3 Seq. ID NO: 31 ATGAGTAGTACCTCTAATTCAATTAGGAGCCCATTGAGTCCGCCCCAGCCGAGACGT ACTCCGCCGCCTTGTACCTCCTCAAGGGAACCGCCCATCGTCCGTGGTACTTGGCTT TTAGGCAGCACCCGTGACTTGTTAAGGGACCCACTGGAGCTAGGGCTGCGTGGATA CGCTGAAGGCGGGGACGTGGTAAGATATGTAGTTGGGTTACCTGGTCGTAGAAGAG AGTTCTTCACGGTTAACCATCCCGATGGGGTTGGGGAACTGCTTAATGCTCCCCGTC ACTTAGACTATCGTAAGGACAGTGAATTTTACCGTGCCATGAGGGATTTATATGGAA ATGGGCTTGTTACCAGTCAAGATGAAACTTGGCTGAGACAGAGAAGGTTCATACAG CCGTTGTTTACTCCACAGAGTGTTGATGGTTACGTCACACCAATGGTCGCGGAGGCT GATAGGGTAGCAATAAGGTGGCACAATTGTACCTCCCGTCTGGTAGATTTGGACGGC GAGATGCGTGCCCTAACATTAGGCGTGGCCGCCAGAATCCTATTCGGAGTTCAAGCC CCGAGGATGCTTCCTATCCTGAGGACTACCCTACCGGTACTTGGTAGGGCCGTTCTG CAACAAGGTGCGTCAGCTATCAGATTTCCTAGCTCTTGGCCTACCCCGGGTAATCGT CGTATCGCCAGTGCAGAATCTCGTCTGGATGGTTTGTGTGATGCTATTATAGAGCGT CGTAGGACAGTAGCCGAGCCAGGTACGGATTTGCTGGGTCGTTTGGTCGCTGCAAG AGAGGACGGTGATACGCTGTCAACGGAGGAAATAAGAGATCAAGTCAAGGTATTTC TCTTGGCTGGTCACGATACAACGGCAACGATGCTGACGTTTGCCTTATACCTGCTTG GTAAGGACGCTGGCGTTCAGGATCAAGCGCGTGACGAAGCGGAACGTGTCTTGGGG GCGGGGACGCCGACCGCAAGCGACGTCCACCGTCTGACATATACTACGATGGTACT GGAGGAGGCGGCGAGACTGTACCCACCGTCTCCCTATTTAACTCGTAGAGCGGTCG AGGAAAGCGAGGTCTGCGGGTACAGAATACCCGCTGGGGCCGATGTCAACCTGGCT CCATGGGTGATCCATCACCGTGCCGATTTATGGCCTGATCCTTTCCGTTTCGATCCCG ACAGATTCACCCCGGATAGGGTAAAAGAAAGACACAAATACGCGTGGTTCCCGTTT GGACACGGACCAAGGGGTTGTATCGGTCAGAGATTCGCAATGCTGGAAGCGGCAGT TACTTTAGCGATTCTTCTAAGAGAATTTGAGTTTAGGTCTCCGCCTGGCAGCGTTCCA TTAACAGTAGACTTACTGTTGCATCCCGCCGGCGAGGTTCCTTGCCGTGTGAGGAGG CGTGTACCTGTGCATTCAGCGGTTCATCGTACTCACCAGCCAAGTTAA >THCdeg_4 Seq. ID NO: 32 ATGAGTAGTGCCCCGGACATTCTTTCTCCCGAGTTTCTGGATAACCCTTATCCTCTTC ACCGTGTGCTACGTGACCACTACCCCGCTTTACACCACGAGGGGACCGACAGCTATC TAATATCAAGGTACGCCGATTGCGCAGAAGCATTTCGTTCACCTAAATTCTCCTCCC GTAACTATGAATGGCAGCTTGAACCGATACACGGTAGAACAATTTTGCAAATGGAA GGGCGTGAGCATTCTACCCATAGAGCATTGCTAAATCCGTTTTTCAGAGGCAACGGA CTAGAGAGATTCATGCCTGCCATTACACACAACGCAGCACAACTAATAGGCGATAT AGTCGCCAGGAATGCAGGGGAATTGCTGGGTGCGGTTGCCAGACAGGGGGAAGCGG AATTGGTATCACAATTCACTAGTCGTTTTCCTATAAACGTAATGGTGGACATGCTGG GACTGCCGAAGTCCGACCACGAAAGGTTTAGAGGCTGGTATTTCTCCATTATGGCTT ATCTTAATAACCTGGCAGGGGACCCTGAAATTAACGCCGCGGCGGAGCGTACACAT GTTGAACTAAGGGAGTACATGCTTCCAATTATTAGAGAGCGTAGGAGTGGAGATGG AGACGACCTTCTATCCAGATTATGTCGTGCCGAAGTTGACGGTGAGCAGATGAGTGA TGAGGAGATAAAGGCCTTTGTCTCTCTACTGCTGGTCGCCGGCGGAGAGACCACAG ATAAGGCAATAGCAAGCATGATCAGAAATTTGATCGACCACCCAGATCAGATGAGG GCGGTTAGAGAAGATCGTTCACTTGCTGATAGGGTAATAGCAGAGACCCTTCGTTAT TCCGGACCCGTACATATGATCATGAGACAAACAGAGGATGAGGTTCAGATAGAGGA CTCTACCATTCCAGCGGGAGCAACCTGCATAATGATGTTAGCAGCCGCGAACAGAG ATGAACGTCATTTTTCAAACCCGGACGAGTTCGATATATTTCGTACGGACCTAAACG TAGACAGAGCCTTCTCAGGGGCGGCCAATCATGTCCAATTTATATTGGGCCGTCATT TTTGCGTCGGGTCCATGTTGGCTAAAACTGAGATGACCATTGCACTTAATCTGGTCTT GGACACAATGGATAGCATAGAATACCAAGATGGTTTTGTTCCCAGAGAGGAGGGGC TGTACACCAGAAGCATCCCGGAGCTTAGGGTAAAATTTGAAGGTAAGTTAGGGTAA >THCdeg_5 Seq. ID NO: 33 ATGAGTAGTAGCACTCCTGCCGCTGCTACATCCTTGGAGAGTGCCTTTGCGGGCGTC GCGGACAATTATAAAGGTTCCGACGTGGACCTTCATGCAATCTATAGAGATATGAG ACGTAACTCTCCTGTCATCGCTGAGGATTTCATGGCACGTCTGGGTGTTCCGAATATT GCAGGCCTAGACGCTAAAAGGCCAACATTTACCCTTTTCAAGTACAAGGACGTGAT GTCTGTCTTGAGGGATGCTACCAATTTCACATCAGGCTTTATCGCGGAAGGATTAGG GGCGTTTTTCGACGGCTTAATCCTGACTGGGATGGATGGTGAAGCACACCGTAGAAC TAGGTCCCTATTGCAGCCGGTTTTCATGCCCGACGTTGTCAACCGTTGGAGGGAAAC GAAAATGGCACCAATAGTCAGGAATGAATATATTGAACCGATGGTCCCGAAAAGGC GTGCTGACCTTATGGACTTTGGACTTCACTTCCCTATACGTCTAATCTACAGTTTGAT AGGGTTCCCAGACAATAGGCCGGAGCAGATCGAACAGTACGCTGCCTGGGCACTTG CCATCCTGGCAGGGCCGCAGGTGGACGCAGAGAAAGCAGCCCAGGCGCGTAAAGCT GCGATGGAAGCCGCCCAGGCGCTTTACGACGCAGTTAAACTTGAAGTTACAGAGGT CCGTAAAAATGGAGCCCAGGGTGACGATCTAATCTGCAGGCTAATTAGAGCTGAGT ATGAAGGCCGTCATCTTGATGATCATGAAGTCACAACCTTTGTCAGGTCACTTCTGC CAGCCGCTGGAGAGACAACTACGAGAACGTTCGGTTCACTGATGGTCGCTCTTCTGG AAAGACCTGAATTACTGGAACGTGTTAGGGCTGATAGATCCTTAGTGCCAAAGGCG ATCGACGAAGCGGTGAGGTTCGAACCAGTAGCTACTTTTAAGGTCAGGCAGGCGGC ACAGGATACGGAAATTGGCGGGTTCTCCATACCGAAGGGAGCAATGGTTCAATGTA TAGTCAGTTCCGCCAACAGGGACGAAGAGGTCTTCGAAAACTCTGAGAGCTTTGAC ATTGATAGAAAGCTGAAACCGTCATTCGGCTTCGGGTTCGGTCCACATATGTGCATA GGGCAGTTCATTGCAAAGGTCGAGTTATCAGTGGCCGTAAACACTATTTTAGATTTA TTGCCAAACCTTCGTTTAGATCCAGACAGGCCGAAACCTAGAATAGTAGGTGCTCAG CTGAGAGGTCCCCACGCGCTTCATGTTATTTGGGACTAA >THCdeg_6 Seq. ID NO: 34 ATGAGTAGTTCTCCCTCAGTGGCAGAGTTAAGCCAGGAGTTGGGAGAAGCATTCCGT CTATCCAGCATGGACGATCCGTATCCGATGTTGGCAGAGAGGAGAAGAGAGACTCC TGTGATGAAAGGGGATATAATGGTGGCCTTAGGTGCGCCAAGCTATATGGGCCAAC ACGCCGGCGAGACTCATACTGTATTCAGGCATGACGACGTAATGGCTATCCTTCGTA ATCACGAAACGTTCTCAAGCAGTATTTGGGAAATTTCTCAAGGGCCACTAATAGGTA GATCCATCCTGGCAATGGACGGGGCAGAGCACAGACAATGGAGGGGATACTTACAG TCTGTATTTGGAGGGAAGCTATTGTCTTCATGGGATGAGTCCATATTCAGGCCCCTT GCGGCAAAGTATGTCGCAGACCTTGCTAGTAAGAGAGGTGCGGACCTAATAGCGAT GGCGTTGGAGTATCCCCTTAGGGCTATCTACGAGATCCTGGGCTTGGAAGATTTTAA AGACAATTATGAGGAATTTCACGCTGACGTACTGACGATTCTACTAGCCCTATGGTC TACACCCGACCCAGCGCAAGCCGACCAGTTCTTGCTACGTTTTCAAAAAGCTACGGA AGCATCTGCTAGGAGTTGGGACCGTCTACTACCCATCGTCCAAAGAAAGAGGGCGG CGGGTGCGAGCAGGAACGACCTTATTTCTAGTCTAATTAGGGCGGAATACGAGGGT GGTGTTTTGGATGATGAACAAATCACCAGTTTTCTTAGGTCTCTATTGCTTGCAGCCA CCGATACTACTACCCGTCAGTTTTTGAATACTTTGACCTTGCTTTTACAGAGGCCAGA TGAGTTGGATCGTATTCGTAGGGATAGGAGCAGATTGAGATTGGCATTGGCGGAAG GGGAAAGGTTGGAACCGCCCGCCCTATTCATACCCCGTATGATAACGAGGGATGTT GTTATTAGGGGTACCGAGTTGACGGCGGGGACCCCCTTACTACTTGCCATCGGGAGC GCGAATCGTGATCCTGAAGCCTACCCACCCGACCCAGATGAATTTCGTATCGATAGA ACGGGACCACACCACGCCACGTTCGGTTTTGGTACTCACATCTGCTCCGGGATGAAC ACTACTCGTCGTGAGATAGCAGCCTTGATCGATGCGATGTTAGACGGGCTACCGGGA CTTCGTGTCGATCCCGACGCTCCCGCGCCACTTATATCAGGGATTCATTTTAGAGGC CCATCCGCACTGCCGGTTGTATGGGATTAA >THCdeg_7 Seq. ID NO: 35 ATGAGTAGTGATTACTCCAGGACACCCGAGTCCCTGCGTCCGGCTGATAGTTATGCC GCGCTATCCTACTCCACAGTTAATGCTGCTCTGCGTAACGATAGAGTATTCTCTTCAA AGATGTACGACTCCACCATTGGAGTGTTTATGGGTCCTACAATCTTGGCTATGAGTG GCACTAAACACAGGGCTCACAGAAACCTTGTATCCGCTGCTTTCAAGCCGCAAAGTC TGAGAGTTTGGGAACCTGATATTGTAAGACCAATTTGTAATGCACTAATTGATGAGT TTGCCGGGACAGGCCACGCAGACCTGGTTCGTGACTTCACGTTTGAATTTCCTACTA GAGTAATAGCTAGACTGCTAGGCTTACCAGCGGAGGATTTGCCATTCTTTAGAAAGG CCGCAGTGGCGATTATCAGTTATGCAGGAAACGTTCCGAGAGCGTTGGAAGCGTCC GAGGACCTGAAGAACTACTTTCTAGGACACATAGAGCAAAGACGTAGTCAGCCTAC CGATGATATTATATCTGATTTAGTTACGGCAGAAGTTGAAGGAGAGCAATTGACCGA TGAGGCAATTTATTCATTCCTGCGTCTGCTGTTACCTGCTGGGTTAGAGACAACCTAC CGTAGTAGTGGAAATTTGCTGTACCTATTATTACGTCACCCAAGGCAATTTGCGGCC GTGCAAGGAAACCATGGTCTTATTCCTCAAGCCGTAGAAGAGGGTCTGCGTTATGAG ACGCCTCTAACGTTTGTCCAGCGTTTCACAACCGAAGACACGGAGCTTGGGGGCGTT CCTGTTCCCGCGGGCGCAGTAGTAGATTTAGTCTTGGGCTCTGCCAACAGGGATGAA GACAGATGGGAACGTCCGGGCGAGTTCGACATATTCAGAAAACCCGTGCCCCATAT AAGTTTTACGGCGGGAGCCCATACTTGTTTAGGACTGCATTTAGCCAGGATGGAGAC GAGGGTTGCTGTCGAGTGCCTACTAACTCGTCTGACTAACTTCAGACTTCAGGATGA AGGAGACCCCCACATAACCGGACAGCCATTCCGTAGTCCGAATCTTCTTCCAGTAAC TTTCGACGTGGTTTAA >THCdeg_8 Seq. ID NO: 36 ATGAGTAGTCCGACGCCAAGGTGGAGGATACCGGTGCTAGGCGATCTTCTTTCAGTT GACCCCGCGAAGCCTGTTCAAAAGGAAATGGCTATGGCGGCGGAACTAGGTCCGTT ATTCGAGCGTAAGATTATAGGGAGCAGACTTACAGTCGTTAGCGGCGTGGACCTAG TCGCTGAGGTCAACGACGAGAAACATTGGGCTAGAGCTTTGGGGAGGCCCATACTG AAGCTAAGAGATGTTGCAGGTGATGGGTTGTTCACAGCGTTCAACAGCGAGCCTGC ATGGGCTAGGGCTCATAGCGTGTTGGGCCCTGGCTTCTCACAAAGCGCATTGAGAAC CTACCATGGCAGTATGACTAGGGTGTTGGATGATTTGGTGGCGACATGGGACGATGC AGCGGCATCAGGTGCCCGTGTCGATGTCGCTCGTGATATGACGAGACTGACTTTCGA TGTGATTGGCAGAGCCGGCTTTGGTCGTGACTTCGGCTCTTTGAGGGGTGATGATCT GGACCCCTTTGCCGCTGCCATGGGTAGAGCACTTGGTTATGTGAATCAAACATCAAA TGACATACCACTTCTACGTATGGTATTCGGTAGGGGCGCGGCCAAAAGGTACCAGA CAGACGTCGCATTTATGCGTGATACCGTAGACGAGCTAGTTGCGAGCAGGGCTGGG CGTGCCGAGAGGAGCGATGATCTTCTTGACCTAATGTTACACAGTGCTGACCCGGAT ACTGGGGAGAGGTTGGACATGGAAAACATTAGGAATCAAGTTCTTACCTTCCTTGTT GCCGGTAATGAGACAACAGCTAGTACATTGGCGTTTGCACTGTATTTTCTGGCTAGA GAGCCCGAAGTTGTCGAAAGAGCCAGGGCCGAGATCGCGGATGTAGTCGGAGACGG TGAGATCGCTTTCGAGCAAGTGGCTAAATTACGTTATGTCAGGAGGGTTGTCGATGA GACGTTAAGACTGTGGCCTGCCGCTCCGGGCTACTTTCGTAAAGTTAGGCATGATAC GGTATTAGGCGGTCGTTATCCCATGCCTAAAGGTTCATGGGTTTTCGTGCTGTTACCA CAGCTTCATCGTGACCCTGTATGGGGTGACGATCCGGAAAGGTTTGACCCCGATAGA TTCGCACCAGACGCTGTGCGTGCAAGGCCTAAAGATGCTTATAGACCGTTTGGCACA GGCCCCAGAAGTTGTATAGGGAGGCAGTTCGCGTTGCACGAGGCGGTACTTGCCCT GGCGACGTTGTTGAGAAGATACGACGTTGCCCCAGACCCAGCATATCGTTTAGATAT CGTAGAAGCTGTAACGCTAAAGCCTAGAGGCTTTGAGCTTACACTACAGAGGAGGT AA >THCdeg_9 Seq. ID NO: 37 ATGAGTAGTTCAGCATCTTCCCAGTCTAACCTAGAGCAAGTCTTTGCCAACGTAGCA TCAAATTATAGAGGAGCAGACATAGACTTGCACGCAGTATATCGTGAAATGAGGGA AAAGTCTCCGGTTCTGCCAGAGAATTTCATGGCCCGTCTAGGTGTGCCCTCAATCGC TGGTCTGGACCCCGACCGTCCTGCCTTCACGCTATTCAAATATGACGACGTTATGGC AGTCATGCGTGATGCTACAAACTTTACTTCAGGCTTTATAGCCGAGGGTTTGGGGTC CTTCTTTGATGGACTTATATTGACAGCAATGGACGGTGAGGCACATAAAAATATACG TTCCTTATTGCAGCCTGTCTTTATGCCAGAAACCGTTAACAGATGGAAAGAGACTAA GATCGACAGAGTGATAAGGGAAGAATACCTGCAACCAATGGTGGCATCCAAAGGGG CGGATATTATGGAGTTTGCTCTGTATTTTCCAATTAGAGTTATTTATTCCCTGATAGG ATTCCCAGAAGATAGACCCGAGGAAATCGAACAATACGCAGCATGGGCGCTCGCAA TCCTGGCGGGCCCACAAGTGGACCCCGAAAAGGCAGTTGCCGCGCGTGGAGCCGCT ATGGAAGCTGCCCAGGCGTTGTATGACGTGGTGAAAGTCGTAGTCGCGCAGAGGCG TTCTCAAGGTGCCACGGGAGATGACTTGATATCCAGGCTGATACGTGCCGAGTACGA AGGTCGTAGCCTGGATGACCACGAGATAACCACGTTCGTCAGGTCCCTACTGCCCGC GGCATCTGAGACAACGACCAGAACATTCGGGACATTGATGACTTTACTATTGGAAA GACCGGAGCTTCTAGCACGTATTCGTGAAGACAGAAGCCTGGTGCCAAAAGCAATT GATGAGGCTGTTAGGTACGAACCTGTAGCAACCTTTAAGGTCAGACAGGCCGCTAA AGACGTTGAGATACGTGGGGTAGCCATTCCTCAAGGAGCCATGGTTAGCTGTATTGT AACATCTGCAAATAGGGACGAAGACGCGTTCGAAAATGCTGATACTTTCAATATCG ATAGAAGAGCGAAACCATCATTCGGTTTCGGATTCGGCCCACACATGTGCATTGGAC AATTTGTAGCCAAGACCGAGATAAATTGCGCTCTAAATGCTATTCTGGACTTAATGC CCAATATACGTCTTGATCCCGATAAACCTGCACCAGAAATCATAGGTGCCCAGCTAA GGGGTCCCCACCATGTACACGTCATTTGGGACTAA >THCdeg_10 Seq. ID NO: 38 ATGAGTAGTACTGCCACAGAATTGAGGGATGCACCTGGGAGTGCGCCAGGCCTACC CAGGAGATCCATGTTATCCCTTTTACCCAGAATGGCACGTGATAGATTGTCAGTTAT GACAAGTGTAGCGGCGCGTTATGGGGACGCCGTGACGTTGCCCTTGGGCTTATCAAC GTTACACTTCTTCAACCACCCCGACTATGCTAAGCACGTACTGGCTGATAATAGCTC AAACTACCACAAGGGCATCGGCTTAATCCACGCGAAGCGTGCGTTAGGTGACGGAC TTCTTACGTCAGAGGGTGAGTTATGGAGAAAACAGAGGAAAACCATTCAGCCGGCA TTTGCTGTTAAAAGGTTGGCTGGACAAGCGGGGGCAATCGCAGAGGAAGCTGATAG GTTGGTAGAGCATCTGCTGGCCCGTCAAGGGAGAGGGCCAGTTGACATCAGGCACG AGATGACTGCCCTTACCCTAGGTGTGTTAGGCCGTACCCTACTTGATGCGGACTTAG GCGCTTTCGGTTCAGTGGGCCACTGGTTCGAGGCTGTACAAGACCAGGCGATGTTTG ACATGATGAGCCTTGGTACTGTACCACTATGGTCTCCCTTGCCCAAGCAACTGAGAT TCAGGAGAGCGAGGAGGGAATTGGAGTCAGTGGTGGACCGTCTAGTAGCTCAGCGA GGGGATAGACCTAGGGCAGACGGCGATGATGTTGTGTCCAGGCTTGTCGATAGTAC AGGAAGGGAGCGTGATCCTGCACTAAGGAGAAAGAGAATGCACGATGAATTGGTG ACTCTGTTACTGGCGGGCCACGAGACAACAGCATCTACCCTTAGCTGGACATTCCAT TTGGCCGATGAACACCCTGAGGTCTGGGAGCGTTTACACGCCGAAGCCGTGGAGGT ACTAGGTGATAGGCGTCCGGTCTTTGAAGATTTACATCGTTTGCGTTACACAAATCG TGTACTAAATGAAGTTATGAGGTTGTACCCTCCAGTTTGGCTGCTTCCTAGAAGAGC TGTCGCTGACGACGTTGTTGGAGGATATAGAGTACCGGCTGGATCTGATGTTTTAAT CTGCCCTTATACGCTACACAGACATCCTGAGTTTTGGGAGCTTCCAAGTAGGTTCGA CCCTGATAGGTTCGATCCGGAAAGGTCTGCCAACAGGCCCAGATATGCTTACATTCC TTTTGGTGCGGGTCCACGTTTTTGCGTTGGTAACAACCTAGGACTAATGGAGGCAGC CTTCGTTATTGCAGCTATAGCAAGAAGAATGAGACTAAGGAAGGTTCCGGGAGGAA CTGTCGTTCCTGAACCAATGTTGACTTTACGTGTTAGAAGTGGGCTGCCTATGACGG TGCACGCGCTTGACCGTTAA >Oxid_1 Seq. ID NO: 39 ATGAGTAGTCAGAGAAGAGATTTCCTTAAGTATTCTGTGGCCCTTGGCGTTGCCTCA GCTTTGCCCCTGTGGTCTAGGGCCGTCTTTGCCGCGGAAAGACCGACTCTTCCGATC CCCGACTTGCTGACGACCGATGCCAGAAATAGAATTCAACTAACCATCGGGGCAGG CCAGAGTACCTTCGGCGGCAAAACCGCCACGACTTGGGGTTACAATGGTAACCTGTT AGGGCCTGCTGTCAAACTACAACGTGGCAAAGCGGTCACGGTAGACATATATAACC AACTAACTGAGGAAACAACGTTGCACTGGCATGGCCTAGAAGTGCCCGGCGAAGTA GATGGAGGTCCCCAGGGCATTATCCCCCCAGGGGGTAAAAGATCAGTCACATTGAA TGTCGACCAGCCTGCGGCTACATGCTGGTTCCATCCACATCAGCACGGGAAGACGG GGAGGCAAGTGGCAATGGGGCTTGCTGGTTTAGTTGTAATAGAGGATGACGAGATC TTGAAACTAATGCTTCCAAAACAATGGGGGATAGACGACGTACCTGTAATCGTTCAA GATAAAAAATTTAGCGCAGATGGGCAAATCGACTACCAGCTGGATGTCATGACAGC GGCAGTGGGATGGTTTGGGGACACACTGCTAACTAACGGGGCTATATACCCCCAGC ACGCCGCTCCAAGGGGTTGGTTACGTCTGCGTCTATTAAACGGTTGCAACGCCCGTA GCTTAAATTTTGCGACCTCAGACAATCGTCCCTTGTATGTAATCGCGAGCGACGGTG GATTATTGCCGGAGCCCGTAAAAGTCTCCGAGTTGCCTGTGCTGATGGGAGAAAGAT TTGAGGTTTTGGTGGAGGTTAACGATAACAAGCCCTTTGATCTAGTTACCCTTCCTGT AAGCCAAATGGGGATGGCCATCGCTCCATTTGACAAACCTCACCCCGTCATGAGAA TTCAACCCATCGCTATAAGTGCGTCTGGTGCGCTTCCAGATACTCTGTCTAGCCTACC AGCGCTACCGTCTCTTGAAGGTTTAACAGTAAGGAAACTGCAACTATCTATGGATCC AATGTTAGATATGATGGGAATGCAAATGTTAATGGAGAAGTACGGTGATCAGGCAA TGGCGGGTATGGACCACTCCCAGATGATGGGCCACATGGGTCACGGCAATATGAAT CATATGAACCATGGGGGCAAATTCGACTTCCATCACGCTAACAAGATTAATGGTCAA GCCTTCGACATGAACAAGCCTATGTTTGCCGCGGCTAAGGGTCAGTACGAAAGATG GGTCATCTCCGGGGTAGGGGACATGATGCTGCATCCGTTCCACATCCATGGCACACA ATTTAGGATTCTTAGTGAAAATGGAAAACCTCCTGCTGCACATAGGGCGGGATGGA AGGATACTGTGAAGGTGGAAGGTAACGTTAGTGAGGTGCTAGTCAAATTCAATCAC GATGCCCCCAAAGAACATGCCTATATGGCCCACTGTCACCTTTTGGAGCATGAGGAT ACGGGAATGATGCTAGGTTTCACAGTC >Oxid_2 Seq. ID NO: 40 ATGTCTAGCAGACTGAGCTTCTTAACGTCATTGGTTACATTGGCGTTGGTATCTAGC ACGTATGCCGGAGTTGGGCCCGTTGTAGATCTTACAGTTTCAAACGCCGTTATTTCA CCTGATGGGTTTGACAGAGACGCGATTGTAGTTAACGGCGTGTTCCCAGCGCCTCTT ATCACAGGTAAGAAAGGTGACAGATTCCAGCTAAATGTGATCGATAACATGACTAA CCATACTATGCTGAAGTCAACAAGTATTCATTGGCATGGGTTTTTTCAAAAAGGTAC TAACTGGGCCGATGGCGGGGCCTTTGTCAACCAATGTCCAATCGCTCCTGGCCACTC CTTCCTATACGATTTCCGTGTACCGGACCAAGCAGGCACATTCTGGTACCACTCACA CCTTTCTACGCAATATTGCGACGGTTTAAGAGGGCCCATCGTGGTATATGACCCCAA CGACCCTCATGCGGACCTGTACGATGTGGATAATGATTCCACTGTGATCACACTTGC CGACTGGTACCACGTTGCCGCCCGTCTTGGGCCCAGATTTCCGCTGGGAGCAGATTC TACGGTTATTAACGGTCTTGGGCGTTCCCTTAGCACGCCTAACGCTGACTTAGCTGT GATCTCAGTCACTCAAGGTAAAAGATATAGGTTCCGTCTAATATCTCTTTCATGCGA CCCCTTCCATACTTTTTCTATCGATGGACATGACTTGACCATTATAGAGGCGGACAG CGTGAACACGGAGCCCTTGGTGGTGGATGCAATTCCAATCTTCGCCGGACAACGTTA TTCTTTTGTCTTGAGCGCCGTCAAGGACATAGATAACTATTGGATACGTGCGGACCC AAACTTTGGAACTACAGGCTTTGCATCAGGTATCAACTCAGCGATCCTTCGTTATGA CGGGGCTGCACCTATTGAACCAACCGCTGTTTTAGCTCCGGTAAGCGTTAATCCCTT GGTTGAGACGGATTTGCACCCGCTTGAGGATATGCCTGTACCCGGTAGACCAACAA AGGGTGGCGTTGATAAAGCAATCAACCTGGATTTTAGTTTTAGCTTCCCTAATTTTTT CATTAACAATGCCACATTTACAAGCCCCACAGTGCCTATCCTGCTACAGATAATGTC CGGCGCGCAAGCCGCGCAGGATTTATTGCCTTCTGGTAGCGTGATTGAACTGCCAGC GCAGTCCACCATAGAACTAACTCTTCCCGCGACGGTCAATGCCCCCGGAGTGCCACA TCCATTTCATTTGCATGGCCACACATTCGCCGTAGTACGTTCCGCCGGTAGCACTGC CTACAATTACGACAACCCTATTTGGCGTGACGTCGTATCCACTGGCACGCCCGCCGC AAATGACAACGTCACTATTAGATTTACAACGGACAATCCCGGACCTTGGTTTTTACA TTGCCACATTGACTTCCACCTTGAGGCTGGCTTCGCCGTGGTATTCGCGGAGGGTGT GCCGCAGACCCAAGTGGCGAATCCAGTACCTCAAGCGTGGGAGGAACTGTGCCCGA TTTATGACGCATTACCGGAAGATGATCAG >Oxid_3 Seq. ID NO: 41 ATGTCTAGTTTTAAAGTCAGCTGTAAGGTCACTAACAACAATGGTGATCAGAACGTA GAAACGAATTCCGTTGATAGAAGGAATGTTCTGCTGGGCCTGGGGGGGCTATATGG TGTCGCTAATGCCATCCCGCTAGCAGCCTCAGCGGCTCCAACGCCACCACCAGACCT AAAGACTTGTGGGAAGGCGACGATAAGTGACGGGCCTCTAGTTGGATACACCTGTT GTCCTCCCCCTATGCCTACAAATTTTGACAATATACCCTACTATAAGTTCCCAAGCAT GACAAAGCTTAGAATCCGTAGTCCGGCACATGCCGTTGACGAAGAATATATCGCTA AATACAATTTAGCGATTTCCAGGATGAAAGATCTAGATAAAACCGAACCCTTAAAC CCTCTAGGGTTCAAGCAGCAGGCTAACATCCACTGTGCGTACTGTAACGGTGCGTAT GTGTTCGGCGACAAGGTACTTCAGGTACATAACTCCTGGCTGTTCTTCCCCTTTCATC GTTGGTATTTATACTTCTATGAGAGGATATTGGGCAAGTTAATAGATGATCCCACGT TTGCTCTGCCATATTGGAATTGGGATCACCCAAAAGGCATGCGTTTGCCGCCGATGT TTGACAGAGAGGGTACATCCATCTATGATGAAAGGAGGAATCAGCAAGTGCGTAAT GGGACCGTCATGGATTTGGGATCATTCGGAGACAAAGTAGAAACGACCCAACTGCA ACTTATGTCCAACAATTTGACTTTGATGTATCGTCAAATGGTCACAAATGCGCCCTG CCCACTACTGTTTTTTGGAGCCCCGTATGTTCTTGGAAACAATGTAGAAGCCCCTGG CACAATTGAAAATATACCGCACATTCCCGTGCATATATGGGCTGGCACGGTGCGTGG CTCCACCTTCCCTAACGGGGATACGTCTTACGGAGAAGACATGGGTAATTTTTACTC CGCAGGTTTAGATAGCGTTTTTTACTGCCATCATGGAAACGTTGATCGTATGTGGAA CGAGTGGAAGGCTATAGGTGGTAAGAGGCGTGACCTGTCTGAAAAAGATTGGTTGA ATAGTGAATTTTTTTTTTATGATGAGAACAAGAAGCCGTATAGGGTCAAAGTTCGTG ATTGCCTGGACGCAAAGAAGATGGGCTACGATTATGCGCCCATGCCCACTCCCTGGC GTAATTTCAAACCCAAAACGAAGGTGAGCGCAGGCAAGGTCAACACATCATCCCTT CCGCCTGTCAACGAGGTTTTTCCCTTGGCTAAAATGGATAAGGTGATTAGTTTTTCA ATAAACAGGCCGGCTAGCTCAAGAACACAGCAAGAAAAAAATGAACAGGAGGAGA TGTTGACATTTGATAACATCAAGTACGACAATCGTGGTTACATTCGTTTTGACGTCTT CTTGAACGTCGACAACAACGTTAACGCGAACGAGCTGGACAAAGTTGAATTCGCTG GAAGCTATACCTCATTACCACATGTGCATCGTGTCGGAGAAAATGATCACACGGCCA CCGTTACCTTCCAGCTAGCCATCACTGAACTACTGGAAGATATCGGCCTAGAAGATG AAGAAACCATAGCTGTGACTCTAGTACCCAAGAAGGGGGGTGAAGGAATTAGTATT GAGAATGTGGAAATTAAATTATTAGACTGT >Oxid_4 Seq. ID NO: 42 ATGTCTGGCCAGAATAAAATGGGTCTTATACTTGTATTTCTGTTTCTGGACGGGTTGC TTGTCTGTTTAGCTGCGGATGTGGATGTACATAACTACACCTTTGTTCTGCAGGAAA AAAACTTTACTAAATGGTGTAGCACTAAAAGTATGCTGGTCGTAAACGGTTCATTCC CTGGGCCAACTATTACAGCCAGAAAGGGGGATACGATATTTGTCAACGTCATAAAT CAAGGGAAGTACGGGTTAACCATCCATTGGCATGGTGTTAAGCAACCAAGGAATCC CTGGAGCGACGGACCCGAATATATAACTCAATGCCCGATTAAACCGGGTACGAACT TCATTTACGAGGTCATTCTGTCAACCGAGGAGGGAACACTGTGGTGGCATGCACACT CCGACTGGACGCGTGCCACCGTGCATGGTGCGTTAGTGATTTTACCCGCTAACGGAA CCACATATCCTTTTCCACCCCCGTACCAGGAGCAGACGATAGTCTTAGCGAGCTGGT TTAAAGGCGATGTGATGGAGGTAATTACATCTTCTGAAGAGACGGGGGTTTTTCCCG CCGCGGCTGACGGGTTTACAATCAATGGCGAACTGGGAGACCTGTACAATTGCAGC AAGGAAACCACATACAGGCTTTCCGTACAGCCGAACAAAACATATTTACTAAGAAT TGTGAATGCAGTCCTAAACGAGGAAAAGTTTTTTGGTATAGCGAAACACACATTGAC AGTAGTTGCTCAGGACGCTTCATATATTAAGCCTATAAATACCTCTTATATAATGAT CACGCCTGGCCAAACGATGGATGTATTATTCACGACCGACCAAACTCCTTCTCACTA CTATATGGTTGCGAGTCCGTTTCACGACGCACTAGACACGTTTGCAAATTTTAGCAC TAATGCAATCATACAATATAATGGGTCCTATAAAGCACCGAAAAGTCCCTTCGTGAA ACCGTTGCCCGTTTATAATGACATCAAGGCAGCAGATAAATTCACGGGGAAACTGC GTTCTCTTGCCAATGAGAAGTTCCCAGTAAACGTCCCCAAGGTCAACGTTAGAAGGA TATTTATGGCAGTCTCACTAAATATCGTTAAGTGTGCAAATAAGAGCTGCAACAATA ATATAGGACACTCTACTTCAGCCTCCCTAAACAACATAAGTTTTGCGCTACCTCAGA CAGATGTACTGCAGGCATATTATAGAAACATCAGCGGCGTATTCGGTAGAGATTTTC CTACAGTTCAGAAGAAGGCTAACTTTTCCTTAAATACAGCCCAAGGCACTCAAGTAC TAATGATAGAGTATGGCGAGGCCGTTGAGATCGTATATCAGGGTACTAATTTGGGA GCCGCAACCAGTCATCCGATGCACCTTCATGGCTTTAACTTCTATCTAGTTGGCACG GGTGCTGGAACGTTCAACAACGTGACTGATCCTCCCAAGTATAACCTGGTCGACCCG CCTGAGTTGAATACTATAAACCTACCACGTATCGGCTGGGCAGCAATTAGGTTTGTC GCGGACAACCCAGGGGTCTGGTTCCTTCACTGTCACTTCGAGAGACATACAACGGA GGGTATGGCAACAGTCGTGATTGTGAAAGATGGCGGAACTACAAACACTTCTATGC TACCAAGTCCCGCGTACATGCCACCATGCAGC >Oxid_5 Seq. ID NO: 43 ATGTCTTCCCGTAAGATTTGTCTAGGGTGTTCACATTCTTTAAGCTCCCAACCCTTTA CATATACAACTCAGAAGACTGTAAGTAGTAGGCGTATCGGTGACTCTCAGTGGCGTC TTAGCCGTGGTTACACCCGTACGCTGACCTCTGCAAGTGCAAGCGTTGCTACAGCTC CCGCTAAGCTACTTACGGTCAATGAAACTCAAAAATGCCTAAGGAACATGGTCCGT GGCGGAGACGTAATTAGCTACATTCTTTCCCATTCTTCCCGTAACGCAGACCAGAAT TTGAAAGATTTAGACAGCTTAATATTGGAGCCTGTCTGCAGTGCTACGCACGAGATG TTCGACGTTTTCGAGATCCCAGAACACATTTTGACTCCGTTTTGCGATAACAGAAAT GTCCCCGAGGAACAAGTCACCCGTAATCCTAATCTGAGAACCGACTGTCTGACGAT GAAGAGGTTTGTGCTATTACAGAGCCTAGTCGCGGTTGCATCCGCCGGAATTGGGCC AGTAGCAGATCTGTACGTAGGAAATAGAATACTGGCTCCGGATGGGTTTAACAGAA GTACAGTTCTAGGAGGTACCAGTTCATCTGATTTTGGATTCCCAGCGCCACTAATCA CCGGCACAAAAGGGGACAGGTTTCAACTGAACGTCATCAATCAATTAACCGACACT ACGATGTTAAGATCAACAAGCATACATTGGCACGGGTTATTCCAGGCTGGCTCATCT TGGGCCGACGGCCCTGTAGGAGTAAATCAATGCCCTATAGCTCCAGGAAACTCATTT CTGTACGACTTTAACGTCCCTGACCAGGCGGGAACTTTCTGGTATCATAGTCATTAT AGCACACAGTACTGTGATGGTCTTAGGGGGGCTTTTGTGGTAAGAGATCCTAACGAT CCACATGCGAGTCTTTACGATGTCGATAATGATGACACAGTTATAACATTGGCTGAT TGGTATCATACGAGCGCTAAAGAGCTATCAGGCTCCTTTCCGGCAGAAGAGGCGAC CTTGATCAATGGGCTGGGTAGGTATAGCGGGGGTCCTACTTCCCCATTAGCTATCGT CAATGTAGAAGCGGGCAAGAGGTACCGTTTCCGTTTGGTATCCATAAGCTGCGATCC ATTCTACACCTTCTCCATTGATGGTCACGATTTGACCATTATAGAGGCGGACGGGGA GAACACTGATCCACTAGTAGTGGACTATCTGGAAATATACGCTGGGCAACGTTACA GCGTGGTGTTAAACGCGAACCAGCCAGTAGACAATTACTGGATTAGGGCAAATTCTT CCAATGGTCCGAGGGACTTTGTTGGCGGCACAAATTCTGCCATACTGCGTTACGCCG GTGCATCAAACTCAGATCCGACAACAGAGCTAGGGCCGCGTAATAATAGGCTTGTT GAGAATAACCTTCATGCTCTGGGATCCCCTGGTGTGCCAGGCACGCATACGATTGGA GAGGCCGATGTAAACATTAATCTTGAAATATTGTTTACGCCACCGAATGTCCTAACC GTTAATGGCGCCCAATTCATTCCACCTACTGCTCCCGTTTTATTGCAGATATTGTCCG GGACAAAACAAGCAACGGATTTGTTACCCCCAGGTTCCGTATATGTTCTGCCTAGAA ACGCGGTAGTTGAGCTAACAATCCCGGGTGGGTCAGGCGGAAGTCCTCATCCGATG CATCTGCATGGCCACGTCTTTGACGTAGTTAGATCAGCTGGATCAGATACCATAAAT TGGGACAATCCGGTCAGAAGAGATGTCGTGAACATTGGGACTAGCACATCTGACAA TGCCACGATTAGGTTCACGACCGACAACCCGGGACCATGGATTTTTCATTGTCATAT CGACTGGCACTTGGAGGTTGGGCTGGCAGTTGTTTTTGCTGAGGATCCGGATACAAT TGAAAATAGTACACATCCCGCTGCGTGGGATGAGCTGTGCCCAATTTACGACAACCT TCCTTCCGACGAGTTA >Oxid_6 Seq. ID NO: 44 ATGAGCTCCACATTGGAAAAGTTCGTAGATGCCTTACCGATCCCAGATACATTAAAG CCGGTACAACAATCTAAAGAAAAAACGTATTACGAGGTCACGATGGAGGAATGTAC GCATCAATTACATAGAGATCTTCCGCCCACAAGGCTATGGGGATATAACGGTTTATT TCCTGGTCCGACGATCGAAGTGAAGAGAAATGAAAACGTATACGTAAAGTGGATGA ATAATTTACCTTCAACACATTTTCTTCCTATAGATCATACCATCCACCACAGCGACTC CCAACATGAAGAGCCTGAGGTAAAGACGGTAGTGCATCTTCATGGCGGTGTTACTCC GGATGACTCCGACGGCTATCCAGAAGCATGGTTCAGCAAGGATTTCGAACAAACGG GCCCGTACTTCAAAAGGGAAGTATATCACTACCCAAACCAGCAGCGTGGTGCCATC CTATGGTATCATGATCATGCAATGGCCTTGACTCGTTTGAATGTTTATGCAGGTCTAG TCGGGGCATACATTATACACGATCCCAAGGAAAAGAGATTAAAACTGCCTTCAGAT GAGTACGATGTACCCCTACTGATCACGGACAGGACAATAAACGAGGATGGTTCTCTT TTTTACCCCAGCGCGCCAGAAAATCCATCCCCCTCACTGCCAAACCCTAGCATTGTC CCGGCATTTTGCGGGGAGACAATCCTTGTGAATGGTAAAGTATGGCCGTACTTGGAG GTCGAACCAAGGAAGTATAGATTTAGGGTTATAAATGCGAGCAACACAAGAACATA TAACTTATCCTTAGACAATGGCGGCGACTTCATTCAAATAGGATCTGATGGGGGCTT GTTACCCCGTTCAGTGAAGTTGAATTCCTTTTCATTAGCACCTGCAGAAAGGTACGA TATAATCATTGACTTTACCGCATACGAAGGTGAGAGCATTATCTTAGCTAATAGTGC TGGCTGCGGGGGGGATGTCAATCCTGAGACGGACGCGAATATTATGCAATTTAGAG TTACAAAGCCTCTGGCCCAAAAGGATGAATCCAGAAAACCAAAGTACTTGGCATCC TATCCGTCAGTTCAACATGAGAGGATTCAAAACATAAGGACACTGAAATTAGCAGG TACGCAAGACGAATATGGTCGTCCGGTACTTTTGCTGAATAATAAGCGTTGGCACGA TCCAGTTACTGAAACGCCTAAGGTGGGTACCACCGAGATTTGGAGCATAATAAATCC CACGAGAGGCACCCATCCCATTCACCTACATCTTGTCAGTTTCAGAGTCTTAGACCG TCGTCCGTTCGATATAGCTCGTTATCAGGAGTCAGGGGAACTTTCCTACACTGGACC TGCTGTACCGCCGCCACCGTCAGAAAAGGGTTGGAAGGACACGATCCAGGCCCATG CGGGTGAAGTTCTAAGAATCGCAGCTACCTTCGGTCCGTACAGCGGGAGGTATGTGT GGCACTGTCATATCTTGGAGCACGAAGACTACGATATGATGAGGCCTATGGATATCA CTGATCCACACAAG >Oxid_7 Seq. ID NO: 45 ATGAGCTCTGTGTTTAGTGCTGCGTTTTCCGCATTCGTTGCCTTAGGTCTAACTCTGG GCGCTTTTGCTGCCGTTGGCCCGGTCGCGGACATCCACATTACCGATGATACCATAG CACCTGACGGATTTAGTAGGGCTGCCGTACTGGCAGGTGGGACCTTCCCAGGGCCCC TAATCACCGGGAACATGGGAGACGCCTTTAAGTTAAACGTCATCGACGAGTTGACG GATGCCTCTATGTTGAAAAGTACCAGTATCCATTGGCACGGCTTCTTTCAGAAGGGA ACGAACTGGGCTGATGGCCCAGCTTTCGTGAATCAATGCCCCATTACAACTGGAAAC TCCTTCTTGTATGACTTCCAAGTGCCAGACCAAGCAGGTACTTATTGGTATCACTCCC ACCTAAGCACTCAGTACTGTGACGGACTGAGAGGTGCCTTCGTGGTTTACGACCCAA GTGATCCGCACAAAGATCTGTACGACGTGGACGATGAATCCACCGTCATAACCCTA GCAGACTGGTACCACACGCTGGCCAGGCAGATTGTGGGAGTGGCGATTAGCGATAC CACGCTTATCAATGGCCTGGGGCGTAATACAGACGGACCCGCAGATGCTGCCTTAG CCGTGATCAATGTAGAAGCTGGCAAAAGATATAGATTTCGTTTAGTAAGCATCAGTT GCGACCCGAATTGGGTGTTTAGTATTGACAATCATGACTTTACGGTTATTGAGGTAG ACGGCGTGAACAGCCAGCCTCTGAATGTTGACAGCGTACAAATATTTGCAGGGCAG AGGTATTCCCTAGTGTTGAACGCGAACCAGCCCGTCGATAACTATTGGATTAGGGCT GATCCTAACCTTGGTACCACAGGGTTCGCGGGTGGAATAAATTCAGCAATTCTACGT TATAAGGGTGCGGCCGTTGCCGAGCCGACTACATCCCAAACCACAAGCACCAAGCC CTTATTGGAGACTGACTTGCACCCCTTGGTTAGTACACCAGTCCCAGGATTACCGCA ACCTGGCGGCACGGATGTAGTCCAAAACCTTATTCTAGGCTTCAATGCTGGGCAGTT CACAATCAATGGCGCATCCTTTGTGCCACCAACAGTTCCAGTTTTGTTACAAATCTTA TCTGGAACAACGAACGCGCAAGACCTGCTACCGTCCGGTAGTGTATTTGAGTTACCG TTGGGAAAAACGGTCGAATTAACCCTGGCAGCCGGCGTTTTAGGCGGACCACACCC GTTTCACTTACACGGTCATAATTTCCATGTCGTCAGGTCCGCTGGACAGGACACGCC CAATTACGACGATCCAATTGTCCGTGACGTTGTCTCAACCGGAGCGTCTGGGGACAA TGTTACAATTAGGTTTACTACCGACAATCCTGGGCCCTGGTTCCTACACTGTCATATC GATTGGCACCTAGAGGCAGGCTTTGCGGTTGTATTCGCAGAGGCAGTGAATGAGAC TAAATCTGGCAATCCTACACCGGCAGCCTGGGATAACCTATGCACTCTTTACGATGC TCTAGCTGATGGTGACAAG >Oxid_8 Seq. ID NO: 46 ATGTCCTCCTGTTTGGCCGCTATATGGTCAAGGAAAAGAGCGGAGCATGCCGCGTCA AGGCTTCCAGCTTTACAGGAGAAAAGGTCCACACTAAGCTACGCGTATGCTAGGTTA GATGGCAGTCTTGCGAGTATGTTTCCAAATAGGTTTTGGTCAAGCGTTAGTCTTGGA GCTAGGATTAAACCGGTGGATGGGAGTAGTGAAGAACCCACCGCAAGGCCCAGCAG CTGTGCCAGGCCCTTCTTACACTCAGCATCATCTGAATCAGGGTTCGTCTCCTCCTCA CGTCCGACCAGCTTTTGCGTTACGTGCTCCCGTCGTTGGAGATGCTGTAGTCTTTTGG CAATGCTGGGATTCAGGTTCTTACACACAAGCGTCCTTGCTGCATTGACTCTTAGTCT AAAGAGTTATGCGGCGATAGGACCGGTTACAGACTTGACCGTCGCTAATGCGAATA TTTCACCCGATGGTTATGAAAGAGCTGCGGTGTTAGCCGGCGGTTCATTTCCCGGCC CACTAATTACTGGCAGAAAGGGGGACCACTTTCAGATTAATGTAGTAGATCAGCTA ACCAACCACACCATGCTTAAAAGCACCTCTATCCATTGGCACGGGCTGTTCCAGAAA GGGACTAACTGGGCAGACGGGCCGGCGTTTGTTAACCAGTGTCCCATCTCCACTGGG AACTCCTTCTTATACGACTTCCATGTTCCTGATCAAGCGGGGACTTTTTGGTATCATT CCCATCTAAGCACACAGTACTGTGATGGTCTAAGGGGTGCCATGGTGGTGTATGACC CCAATGACCCTCACAAGAACCTTTATGACGTAGATAATGACGATACCGTAATAACCC TAGCAGATTGGTATCATGTAGCCTCTAAGCTGGGGCCTGCTGTCCCTTTTGGGGGGG ACTCAACCTTGATAAATGGCAAGGGTCGTAGCACTGCAACACCAACCGCCGACCTT GCTGTCATTAGTGTAACTCAAGGTAAAAGATATAGGTTCCGTCTGGTGTCACTTTCA TGCGACCCGAATTTCACGTTTAGTATAGATGGTCATGCCCTGACCGTAATAGAGGCC GATGCTGTTTCAACTCAGCCATTAACTGTCGACAGTATCCAAATATTCGCGGGTCAA AGGTACTCCTTTGTGCTTAATGCCAATCAGTCCGTTGATTCATACTGGATTCGTGCCC AGCCATCCCTTGGTAATGTGGGCTTTGATGGAGGGCTTAATTCTGCGATCCTTCGTTA TGACGGGGCTGCGCCGACCGAACCATCCGCGCTAGCTGTTCCAGTCTCTACTAATCC TTTGGTTGAGACGGCACTGAGGCCGCTTAATTCAATGCCCGTCCCCGGTAAGGCTGA GGTGGGCGGTGTGGATAAAGCGATTAACCTTGCGTTTAGTTTCAATGGCACGAACTT TTTCATCAATGGGGCAACGTTTGTGCCGCCCGCCGTGCCCGTTCTACTACAGATCAT GAGTGGCGCCCAGAGTGCTAGTGATCTTCTTCCTAGCGGCTCAGTGTTTGTGCTACC CAGTAACGCTACCATCGAATTAAGTTTTCCAGCAACTGCAAACGCCCCAGGCGCTCC ACATCCCTTCCACCTACATGGACACACGTTCGCGGTAGTACGTTCTGCTGGTTCCGC GGAGTATAATTATGAAAATCCTATATGGAGAGACGTTGTTTCAACCGGTTCTCCGGG AGACAATGTCACCATACGTTTCAGGACCGATAATCCGGGCCCCTGGTTTCTGCATTG TCATATCGATCCCCATCTGGAGGCCGGCTTTGCGGTGGTTATGGCGGAGGACACTAG GGACGTCAAGGCCGACAATCCCGAACCTAAAGCCTGGGACGATCTTTGCCCCACAT ACAATGCGCTAGCAGTGGATGACCAA >Oxid_9 Seq. ID NO: 47 ATGTTTCCAGGGGCGCGTATTCTGGCCACCCTGACGTTGGCACTGCATCTGCTGCAC GGTACCAATGCCGCAATAGGACCCACTGGAGACATGTACATAGTTAACGAAGACGT GTCCCCTGACGGCTTCACCAGGTCCGCAGTAGTTGCTAGGAGTGATCCTACCACAAA CGGGACATCCGAAACTCTAACGGGTGTCTTAGTTCAGGGGAACAAGGGAGACAACT TCCAATTGAACGTGCTGAACCAGTTATCAGACACAACTATGCTAAAAACGACAAGC ATTCATTGGCACGGCTTTTTTCAATCTGGATCCACCTGGGCCGACGGCCCAGCCTTTG TAAACCAATGTCCAATAGCTAGCGGTAATTCTTTCCTTTACGATTTTAATGTACCAGA CCAGGCCGGCACGTTCTGGTACCACAGTCATCTGTCAACCCAGTACTGTGACGGTTT GAGGGGACCATTTATCGTTTACGACCCAAGCGATCCCCACCTGTCTCTATACGACGT CGACAATGCGGACACTATCATAACGCTGGAAGACTGGTACCACGTAGTGGCACCTC AGAACGCCGTATTGCCGACGGCCGATAGCACACTAATTAACGGCAAAGGCCGTTTC GCCGGGGGTCCTACAAGCGCCTTAGCGGTCATCAATGTTGAGTCTAATAAACGTTAC AGATTCCGTCTTATATCCATGTCCTGTGACCCTAATTTTACGTTTAGTATAGACGGAC ATAGCCTACAAGTGATTGAGGCCGATGCCGTGAACATTGTACCGATAGTAGTGGATT CCATCCAGATATTCGCCGGACAAAGGTACAGCTTTGTACTTAACGCTAACCAGACCG TGGACAACTACTGGATCAGAGCTGATCCGAATTTGGGCAGCACTGGTTTCGACGGA GGTATCAACTCTGCTATTTTAAGGTATGCTGGAGCAACGGAAGATGACCCCACGACG ACAAGTTCCACCTCAACTCCATTAGAAGAAACAAACTTGGTACCCCTAGAGAATCCT GGGGCGCCAGGACCGGCGGTACCCGGCGGTGCAGACATAAATATCAATCTTGCCAT GGCTTTCGACGTGACGAATTTCGAATTAACGATTAACGGATCCCCTTTCAAAGCACC TACCGCCCCCGTACTTTTACAGATATTGTCAGGAGCAACGACGGCCGCTTCCTTGCT GCCATCAGGGTCCATTTACTCACTAGAAGCCAATAAAGTAGTGGAGATTTCCATACC TGCTCTAGCTGTGGGGGGTCCGCATCCTTTCCACTTACACGGGCATACATTTGACGTT ATACGTTCAGCGGGGAGTACGACTTACAATTTTGACACTCCCGCTCGTAGGGATGTC GTTAATACAGGAACGGACGCTAATGATAATGTAACAATAAGATTTGTTACCGACAA CCCAGGGCCGTGGTTTCTGCATTGCCACATAGACTGGCACTTAGAGATAGGGCTGGC CGTCGTTTTCGCCGAGGACGTTACTAGCATAACCGCACCTCCAGCGGCGTGGGATGA TTTGTGTCCCATCTATGACGCATTATCTGATAGCGACAAGGATAATCCTAGGTTTGG ATTTGCACCAGCGACAGGAGGTAAAGCAACGGGCAGGAGAAATTGGTTCTCAAAGG CTAGGCGTAGAGCAATTTTGGTTCCCTATTTAAAACTTTTAAAATTGGGGTTGGTGA TGGTCTTCTATATAAGAGCAGAAAGGAACCATGGTAGACTTTCCCAATCTACACCTC CGAATCGTAGGGTAGATCAGCGTGAATTAATTACTAACACATGGGTGGAGAGGTTTT TCCTGCACCGTCTAATGTTTCTGAAGCTTTTTGTTGGAACCGCATGTTTCATGCACAT CTTCAATTCAGTTAGCTCACTAGGGATGTGTACGTTGAGGACCAGCCATGGGTCCTC CGAGTCATTAGCTTCTCCATCAGCGACCATGATGTTAGGAGGCGGCCTAACTCTTCT TAGTGCTAACATAAGACTTTGGTGTTATGCCGAGATGAGAGATTTGTACGACTTCGA AGTTAATATCAAAAAGGCCCACCGTCTTGTAACGACTGGGCCGTATAGTGTTTCTAT GGTTATGTTTAGCAAGGATCATTGGTTGTATCAATGCGGTCTGCGTTCCATGGTTGG CGTTGTGCTAAGTTGTATATGGTGCGCGGAAGTTGTACTGATCAACGGAATTATGGT CCCGGCACGTATGAAGGTGGAAGACGACGGATTGAGAAGGCACTTCGGGCGTGAGT GGGATGAATATGCATCACGTGTGGCCTATAGGTTGGTCCCCGAGATTTAT >Oxid_10 Seq. ID NO: 48 ATGTCAAGTAAGAGCTTTATCTCTGCCGCGACCCTACTGGTCGGAATACTTACGCCG AGTGTGGCGGCTGCTCCACCTAGCACCCCTGAGCAAAGGGACCTGTTGGTTCCCATT ACAGAAAGGGAGGAAGCTGCTGTTAAAGCGCGTCAGCAGTCTTGCAACACTCCCTC AAACCGTGCATGCTGGACGGATGGCTATGACATCAATACAGACTATGAAGTAGATT CTCCTGATACGGGTGTTGTTCGTCCCTACACTTTGACGCTGACCGAGGTTGATAACT GGACTGGGCCTGATGGTGTCGTCAAGGAAAAGGTTATGCTGGTAAACAATTCAATA ATCGGACCCACAATTTTTGCCGATTGGGGTGATACCATCCAAGTCACGGTGATTAAT AACCTTGAGACCAATGGAACGAGTATTCATTGGCACGGCCTACATCAGAAGGGTAC GAACTTGCACGATGGAGCTAATGGGATTACTGAATGCCCCATCCCGCCCAAGGGGG GCAGAAAGGTTTATAGATTCAAAGCACAGCAATATGGAACGAGTTGGTATCATAGT CACTTTTCCGCGCAGTACGGCAACGGTGTGGTTGGCGCGATACAGATCAACGGGCC GGCCAGTTTACCATACGATACGGACCTGGGCGTTTTTCCTATCAGCGATTATTATTAT TCCTCAGCGGATGAGCTAGTTGAATTGACCAAAAACAGCGGTGCACCCTTTTCAGAT AATGTCCTTTTTAACGGAACGGCAAAGCACCCAGAAACAGGCGAGGGCGAGTACGC AAATGTAACGTTAACCCCAGGAAGGAGGCATCGTTTGCGTCTGATTAACACGAGTGT TGAAAACCATTTCCAAGTCTCTCTAGTTAATCATACCATGACGATCATTGCCGCCGA TATGGTTCCAGTAAATGCTATGACCGTTGATTCACTGTTCCTGGGCGTCGGACAAAG GTACGACGTAGTAATAGAAGCTAGTAGAACTCCAGGGAATTATTGGTTCAATGTGA CATTCGGGGGCGGCCTGTTGTGCGGAGGCAGTAGGAATCCTTACCCAGCTGCAATAT TTCACTATGCAGGCGCCCCTGGTGGACCGCCGACTGATGAAGGAAAAGCGCCGGTG GATCACAACTGCTTGGATCTGCCGAACCTTAAACCTGTTGTTGCTCGTGATGTGCCA TTATCTGGTTTCGCCAAGAGGCCCGACAACACTTTAGACGTCACTTTGGACACGACT GGAACTCCCCTTTTCGTCTGGAAGGTAAACGGTAGTGCTATTAACATAGACTGGGGC CGTCCGGTCGTGGATTACGTACTAACACAAAACACTTCTTTCCCACCCGGTTACAAT ATAGTCGAGGTCAACGGCGCAGATCAGTGGTCATACTGGTTGATTGAGAATGACCC AGGTGCGCCATTCACGCTACCGCACCCGATGCACCTACATGGGCATGACTTTTATGT ACTAGGTAGAAGTCCGGATGAATCACCTGCTAGCAATGAACGTCACGTATTTGATCC CGCCCGTGATGCGGGATTACTGTCCGGGGCGAACCCAGTGAGGCGTGATGTTACTAT GTTGCCTGCGTTTGGATGGGTTGTGCTGGCCTTCAGGGCTGACAACCCCGGGGCATG GCTTTTTCATTGCCATATAGCATGGCACGTATCCGGCGGGCTAGGTGTTGTCTACCTA GAGCGTGCAGACGACCTGAGGGGAGCGGTATCAGACGCGGACGCGGATGACTTGGA TAGGCTTTGCGCTGATTGGAGGAGATACTGGCCGACAAATCCGTATCCCAAATCAGA CTCTGGTCTT >Oxid_11 Seq. ID NO: 49 ATGTCATCCCGTTTCCAGAGCCTATTTTTCTTTGTGCTGGTAAGCTTGACTGCGGTGG CGAATGCGGCTATTGGGCCGGTGGCTGACCTTACACTTACAAACGCACAAGTTTCCC CAGATGGCTTCGCTAGAGAAGCGGTCGTGGTTAACGGAATCACCCCAGCACCATTG ATTACGGGGAACAAGGGGGACAGATTTCAGTTAAATGTGATCGACCAGCTTACTAA CCACACGATGTTGAAGACGTCTTCTATACACTGGCATGGTTTTTTCCAGCAGGGTAC TAACTGGGCAGATGGCCCTGCTTTCGTTAACCAGTGTCCGATTGCGTCCGGTCATAG TTTTTTGTACGACTTTCAGGTCCCTGATCAAGCGGGGACGTTCTGGTATCACTCACAC CTAAGTACCCAATACTGTGACGGACTGCGTGGACCGTTCGTGGTGTACGACCCTAAT GATCCCCATGCGAGCCTTTATGACATCGACAATGACGATACTGTCATAACTCTGGCG GACTGGTACCATGTAGCCGCGAAATTAGGTCCACGTTTCCCATTCGGTTCAGATAGC ACCCTAATAAACGGCCTTGGCAGAACTACCGGAATTGCGCCGTCTGACCTTGCAGTC ATCAAAGTGACACAGGGCAAGCGTTACCGTTTCCGTCTGGTCTCTTTGTCCTGTGAC CCAAACCACACATTCTCCATTGACAATCACACCATGACGATCATCGAGGCCGACTCT ATCAATACGCAGCCACTAGAGGTGGATAGCATCCAGATATTCGCTGCTCAGCGTTAT TCTTTCGTGCTGGACGCTAGCCAACCGGTGGATAACTACTGGATAAGAGCAAATCCG GCGTTCGGTAACACCGGGTTTGCTGGTGGGATAAACTCTGCCATACTTAGATACGAT GGTGCACCAGAAATCGAGCCTACTTCTGTCCAAACAACCCCGACTAAGCCTCTGAAT GAAGTGGATTTGCACCCTTTGTCACCGATGCCAGTACCAGGATCTCCAGAACCGGGA GGAGTGGATAAGCCACTTAACCTAGTGTTCAATTTCAATGGGACAAACTTTTTCATT AATGACCACACCTTTGTGCCACCCTCTGTGCCCGTACTTTTGCAAATATTGAGTGGTG CTCAGGCGGCGCAAGACCTGGTCCCGGAGGGGTCCGTGTTCGTTCTTCCTAGTAATT CTAGCATTGAGATCTCCTTTCCAGCAACCGCTAATGCTCCAGGTTTCCCGCATCCATT CCATCTACACGGACACGCATTTGCGGTTGTAAGGAGTGCGGGGAGTTCAGTTTACAA CTATGACAACCCCATATTCAGGGACGTAGTAAGCACAGGACAACCAGGTGACAATG TGACTATAAGATTCGAGACCAATAACCCCGGTCCTTGGTTCTTACATTGCCACATAG ACTTTCACTTAGACGCGGGTTTTGCAGTGGTCATGGCCGAGGATACTCCTGATACTA AAGCCGCGAATCCAGTGCCTCAAGCCTGGTCTGATTTATGTCCGATCTATGATGCGC TGGATCCTTCCGATTTA >Oxid_12 Seq. ID NO: 50 ATGAGCTCCGGACTTCAACGTTTCAGTTTCTTCGTTACGTTAGCATTAGTGGCCCGTT CACTTGCTGCAATCGGACCAGTGGCATCCCTGGTAGTTGCAAACGCTCCAGTGAGTC CGGACGGTTTTCTTAGGGACGCCATTGTGGTAAACGGAGTGGTACCGAGTCCACTAA TAACTGGCAAAAAAGGAGACCGTTTCCAGCTGAATGTCGATGATACCCTGACAAAT CATAGTATGCTTAAGAGCACGAGCATACACTGGCACGGTTTTTTTCAAGCAGGAACA AACTGGGCCGACGGACCGGCTTTCGTCAATCAATGTCCCATCGCTAGTGGGCACTCC TTCCTATACGATTTTCATGTTCCAGACCAAGCGGGGACGTTTTGGTACCATAGTCATC TAAGTACCCAATACTGCGATGGGCTTCGTGGGCCTTTCGTAGTGTACGACCCAAAGG ATCCCCATGCGTCCAGGTACGATGTCGACAATGAAAGCACGGTGATTACGCTGACA GATTGGTATCATACCGCTGCGAGGTTAGGACCGCGTTTTCCCCTTGGAGCAGACGCC ACTCTAATCAATGGGTTGGGACGTTCTGCCAGTACACCGACCGCCGCGCTGGCTGTT ATAAACGTACAACATGGGAAAAGATACAGGTTTAGGTTAGTATCTATCAGTTGTGAC CCTAATTATACATTCTCTATAGATGGTCATAACCTTACGGTCATTGAAGTTGACGGC ATCAATTCCCAGCCCTTACTGGTTGATAGTATCCAGATCTTCGCTGCCCAGAGATATT CTTTTGTGCTGAATGCTAATCAGACAGTTGGTAACTATTGGGTCAGGGCCAACCCTA ACTTTGGGACGGTTGGTTTTGCTGGGGGGATCAACTCAGCCATACTAAGGTACCAAG GTGCGCCCGTAGCAGAACCTACTACCACGCAGACAACCAGTGTAATCCCTTTGATTG AGACCAATCTGCATCCGCTTGCACGTATGCCCGTACCGGGCTCACCGACACCAGGA GGAGTGGACAAAGCCTTAAATCTAGCTTTTAACTTCAATGGAACAAATTTCTTCATC AACAACGCCACGTTTACACCACCAACGGTGCCTGTATTACTTCAGATCTTAAGCGGC GCCCAGACGGCACAGGATTTGCTGCCAGCAGGATCAGTATATCCTCTACCCGCGCAC TCAACCATAGAAATAACGCTTCCTGCCACAGCACTTGCTCCTGGGGCTCCACACCCT TTCCACCTACATGGGCACGCATTCGCCGTAGTGAGATCTGCGGGATCCACGACTTAC AATTACAATGACCCCATCTTCCGTGATGTGGTGAGCACAGGGACACCAGCAGCGGG AGATAATGTTACTATTCGTTTCCAAACTGACAACCCGGGGCCATGGTTTCTGCACTG CCACATAGATTTTCATCTTGACGCCGGCTTTGCGATCGTGTTCGCCGAGGATGTCGC AGACGTGAAGGCCGCCAACCCCGTTCCAAAGGCGTGGTCAGATCTATGTCCGATAT ATGACGGCTTATCTGAAGCCAATCAA >p450_1 Seq. ID NO: 51 MAADSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDISKSLTNLSK VYGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGIFPLAERANRGFGIVFSNGKK WKEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVIC SIIFHKRFDYKDQQFLNLMEKLNENIKILSSPWIQICNNFSPIIDYFPGTHNKLLKNVAFMK SYILEKVKEHQESMDMNNPQDFIDCFLMKMEKEKHNQPSEFTIESLENTAVDLFGAGTE TTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRSHMPYTDAVVHEVQRYI DLLPTSLPHAVTCDIKFRNYLIPKGTTILISLTSVLHDNKEFPNPEMFDPHHFLDEGGNFK KSKYFMPFSAGKRICVGEALAGMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASVP PFYQLCFIPV >p450_2 Seq. ID NO: 52 MAADSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDISKSLTNLSK VYGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGIFPLAERANRGFGIVFSNGKK WKEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVIC SIIFHKRFDYKDQQFLNLMEKLNENVKILSSPWIQICNNFSPIIDYFPGTHNKLLKNVAFM KSYILEKVKEHQESMDMNNPQDFIDCFLMKMEKEKHNQPSEFTIESLENTAVDLFGAGT ETTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRSHMPYTDAVVHEVQRY IDLLPTSLPHAVTCDIKFRNYLIPKGTTILISLTSVLHDNKEFPNPEMFDPHHFLDEGGNFK KSNYFMPFSAGKRICVGEALARMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASVP PFYQLCFIPV >p450_3 Seq. ID NO: 53 MAADSFVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIDIKDISKSLTNLSK VYGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGHFPLAERANRGFGIVFSNGKK WKEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVIC SIIFRKRFDYKDQQFLNLMEKLNENVKILSSPWIQIYNNFSPIIDYFPGTHNKLLKNVAFM KSYILEKVKEHQESMDMNNPQDFIDCFLMKMEKEKHNQPSEFTIESLENTAADLFGAGT ETTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRSHMPYTDAVVHEVQRY IDLLPTSLPHAVTCDIKFRNYLIPKGTTILISLTSVLHDNKEFPNPEMFDPHHFLDEGGNFK KSNYFMPFSAGKRICVGEALARMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASVP PFYQLCFIPV >p450_4 Seq. ID NO: 54 MAADLVVFLALTLSCLILLSLWRQSSGRGKLPPGPTPLPIIGNFLQIDVKNISQSFTNFSKA YGPVFTLYLGSKPTVILHGYEAVKEALIDRGEEFAGRGSFPMAEKIIKGFGVVFSNGNRW KEMRRFTLMTLRNLGMGKRNIEDRVQEEAQCLVEELRKTKGSPCDPTFILSCAPCNVICS IIFQNRFDYKDKEFLILMDKINENVKILSSPWLQVCNSFPSLIDYCPGSHHKIVKNFNYLK SYLLEKIKEHKESLDVTNPRDFIDYYLIKQKQVNHIEQSEFSLENLASTINDLFGAGTETTS TTLRYALLLLLKYPDVTAKVQEEIDRVVGRHRSPCMQDRSHMPYTDAMIHEVQRFIDLL PTSLPHAVTCDIKFRKYLIPKGTTVITSLSSVLHDSKEFPNPEMFDPGHFLNANGNFKKSD YFMPFSTGKRICAGEGLARMELFLILTTILQNFKLKSLVHPKEIDITPVMNGFASLPPPYQ LCFIPL >p450_5 Seq. ID NO: 55 MAAILGVFLGLFLTCLLLLSLWKQNFQRRNLPPGPTPLPIIGNILQIDLKDISKSLRNFSKV YGPVFTLYLGRKPAVVLHGYEAVKEALIDHGEEFAGRGVFPVAQKFNKNCGVVFSSGR TWKEMRRFSLMTLRNFGMGKRSIEDRVQEEARCLVDELRKTNGVPCDPTFILGCAPCN VICSIVFQNRFDYKDQEFLALIDILNENVEILGSPWIQICNNFPAIIDYLPGRHRKLLKNFA FAKHYFLAKVIQHQESLDINNPRDFIDCFLIKMEQEKHNPKTEFTCENLIFTASDLFAAGT ETTSTTLRYSLLLLLKYPEVTAKVQEEIDHVIGRHRSPCMQDRHHMPYTDAVLHEIQRYI DLLPTSLPHALTCDMKFRDYLIPKGTTVIASLTSVLYDDKEFPNPEKFDPSHFLDENGKF KKSDYFFPFSTGKRICVGEGLARTELFLFLTTILQNFNLKSPVDLKELDTNPVANGFVSVP PKFQICFIPI >p450_6 Seq. ID NO: 56 MAAALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFC MFDMECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMK SAISIAEDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDV FGAYSMDVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNI CVFPREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVA QSIIFIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDM VVNETLRLFPIAMRLERVCKKDVEINGMFIPKGVVVMIPSYALHRDPKYWTEPEKFLPE RFSKKNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLS LGGLLQPEKPVVLKVESRDGTVSGA >p450_7 Seq. ID NO: 57 MAADLIPNLAVETWLLLTKLEFGFYIFPFIYGTHSHGLFKKLGIPGPTPLPFLGNILSYRKG FCMFDMECHKKYGKVWGFYDGRQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGF MKSAISIAEDEEWKRIRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREADTGKPVTLK DVFGAYSMDVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSIIVFPFLIPILEVL NICVFPREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLEL VAQSIIFIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYL DMVVNETLRLFPVAMRLERVCKKDVEINGMFIPKGVVVMIPSYALHRDPKYWTEPEKF LPERFSKKNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPL KLRLGGLLQPEKPIVLKVESRDGTVSGA >p450_8 Seq. ID NO: 58 MAAALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNIWSYRKGF CMFDMECHKKYGKVWGFYDGRQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFM KSAISIAEDEEWKRLRSLLSPTFTSGKLKEMVPLIAQYGDVLVRNLRLEAETGKPVTMKV ITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSIIVFPFLTPILEVLNISVFPRAVTS FLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSIIFIFAGY ETTSSVLSFITYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVVNETLRLF PIAMRLERVCKKDVEINGMFIPKGVVVMIPSYALHHDPKYWTEPEKFLPERFSKKNKDN IDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLRLGGLLQPEK PIVLKVESRDGTVSGA >p450_9 Seq. ID NO: 59 MAAELIPSFSMETWVLLATSLVLLYIYGTYSYGLFKKLGIPGPRPVPYFGSTMAYHKGIP EFDNQCFKKYGKMWGFYEGRQPMLAITDPDIIKTVLVKECYSVFTNRRIFGPMGIMKYA ISLAWDEQWKRIRTLLSPAFTSGKLKEMFPIIGQYGDMLVRNLRKEAEKGNPVNMKDM FGAYSMDVITGTAFGVNIDSLNNPHDPFVEHSKNLLRFRPFDPFILSIILFPFLNPVFEILNI TLFPKSTVDFFTKSVKKIKESRLTDKQMNRVDLLQLMINSQNSKEIDNHKALSDIELVAQ STIFIFGGYETTSSTLSFIIYELTTHPHVQQKVQEEIDATFPNKAPPTYDALVQMEYLDMV VNETLRMFPIAGRLERVCKKDVEIHGVTIPKGTTVLVPLFVLHNNPELWPEPEEFRPERFS KNNKDSINPYVYLPFGTGPRNCLGMRFAIMNIKLALVRILQNFSFKPCKETQIPLKLYTQ GLTQPEQPVILKVVPRGLGPQVEPDFL >p450_10 Seq. ID NO: 60 MAADSFPLLAALFFILAATWFISFRRPRNLPPGPFPYPIVGNMLQLGTQPHETFAKLSKKY GPLMSIHLGSLYTVIVSSPEMAKEINIHKYGQVFSGRTVAQAVHACGHDKISMGFLPVGG EWRDMRKICKEQMFSHQSMEDSQWLRKQKLQQLLEYAQKCSERGRAIDIREAAFITTL NLMSATLFSMQATEFDSKVTMEFKEIIEGVASIVGVPNFADYFPILRPFDPQGVKRRADV YFGRLLAIIEGFLNERVESRRTNPNAPKKDDFLETLVDTLQTNDNKLKTDHLTHLMLDLF VGGSETSTTEIEWIMWELLANPEKMAKMKAELKSVMGEEKVVDESQMPRLPYLQAVV KESMRLHPPGPLLLPRKAESDQVVNGYLIPKGAQVLINAWAIGRDHSIWKNPDSFEPERF LDQKIDFKGTDYELIPFGSGRRVCPGMPLANRILHTVTATLVHNFDWKLERPEASDAHR GVLFGFAVRRAVPLKIVPFKV >p450_11 Seq. ID NO: 61 MAADPFPLVAAALFIAATWFITFKRRRNLPPGPFPYPIVGNMLQLGSQPHETFAKLSKKY GPLMSIHLGSLYTVIISSPEMAKEIMHKYGQVFSGRTIAQAVHACDHDKISMGFLPVGAE WRDMRKICKEQMFSHQSMEDSQNLRKQKLQQLLEYAQKCSEEGRGIDIREAAFITTLNL MSATLFSMQATEFDSKVTMEFKEIIEGVASIVGVPNFADYFPILRPFDPQGVKRRADVYF GRLLGLIEGYLNERIEFRKANPNAPKKDDFLETLVDALDAKDYKLKTEHLTHLMLDLFV GGSETSTTEIEWIMWELLASPEKMAKVKAELKSVMGGEKVVDESMMPRLPYLQAVVK ESMRLHPPGPLLLPRKAESDQVVNGYLIPKGAQVLINAWAMGRDPSLWKNPDSFEPERF LDQKIDFKGTDYELIPFGSGRRVCPGMPLANRILHTVTATLVHNFDWKLERPEASDAHK GVLFGFAVRRAVPLKIVPIKA >p450_12 Seq. ID NO: 62 MAADSFPLLAALFFIAATITFLSFRRRRNLPPGPFPYPIVGNMLQLGANPHQVFAKLSKR YGPLMSIHLGSLYTVIVSSPEMAKEILHRHGQVFSGRTIAQAVHACDHDKISMGFLPVAS EWRDMRKICKEQMFSNQSMEASQGLRRQKLQQLLDHVQKCSDSGRAVDIREAAFITTL NLMSATLFSSQATEFDSKATMEFKEIIEGVATIVGVPNFADYFPILRPFDPQGVKRRADVF FGKLLAKIEGYLNERLESKRANPNAPKKDDFLEIVVDIIQANEFKLKTHHFTHLMLDLFV GGSDTNTTSIEWAMSELVMNPDKMARLKAELKSVAGDEKIVDESAMPKLPYLQAVIKE VMRIHPPGPLLLPRKAESDQEVNGYLIPKGTQILINAYAIGRDPSIWTDPETFDPERFLDN KIDFKGQDYELLPFGSGRRVCPGMPLATRILHMATATLVHNFDWKLEDDSTAAADHAG ELFGVAVRRAVPLRIIPIVKS >CPR_1 Seq. ID NO: 63 MAAGDSHVDTSSTVSEAVAEEVSLFSMTDMILFSLIVGLLTYWFLFRKKKEEVPEFTKIQ TLTSSVRESSFVEKMKKTGRNIIVFYGSQTGTAEEFANRLSKDAHRYGMRGMSADPEEY DLADLSSLPEIDNALVVFCMATYGEGDPTDNAQDFYDWLQETDVDLSGVKFAVFGLGN KTYEHFNAMGKYVDKRLEQLGAQRIFELGLGDDDGNLEEDFITWREQFWPAVCEHFGV EATGEESSIRQYELVVHTDIDAAKVYMGEMGRLKSYENQKPPFDAKNPFLAAVTTNRK LNQGTERHLMHLELDISDSKIRYESGDHVAVYPANDSALVNQLGKILGADLDVVMSLN NLDEESNKKHPFPCPTSYRTALTYYLDITNPPRTNVLYELAQYASEPSEQELLRKMASSS GEGKELYLSWVVEARRHILAILQDCPSLRPPIDHLCELLPRLQARYYSIASSSKVHPNSVH ICAVVVEYETKAGRINKGVATNWLRAKEPAGENGGRALVPMFVRKSQFRLPFKATTPVI MVGPGTGVAPFIGFIQERAWLRQQGKEVGETLLYYGCRRSDEDYLYREELAQFHRDGA LTQLNVAFSREQSHKVYVQHLLKQDREHLWKLIEGGAHIYVCGDARNMARDVQNTFY DIVAELGAMEHAQAVDYIKKLMTKGRYSLDVWS >CPR_2 Seq. ID NO: 64 MAAPFGIDNTDFTVLAGLVLAVLLYVKRNSIKELLMSDDGDITAVSSGNRDIAQVVTEN NKNYLVLYASQTGTAEDYAKKFSKELVAKFNLNVMCADVENYDFESLNDVPVIVSIFIS TYGEGDFPDGAVNFEDFICNAEAGALSNLRYNMFGLGNSTYEFFNGAAKKAEKHLSAA GAIRLGKLGEADDGAGTTDEDYMAWKDSILEVLKDELHLDEQEAKFTSQFQYTVLNEIT DSMSLGEPSAHYLPSHQLNRNADGIQLGPFDLSQPYIAPIVKSRELFSSNDRNCIHSEFDL SGSNIKYSTGDHLAVWPSNPLEKVEQFLSIFNLDPETIFDLKPLDPTVKVPFPTPTTIGAAI KHYLEITGPVSRQLFSSLIQFAPNADVKEKLTLLSKDKDQFAVEITSKYFNIADALKYLSD GAKWDTVPMQFLVESVPQMTPRYYSISSSSLSEKQTVHVTSIVENFPNPELPDAPPVVGV TTNLLRNIQLAQNNVNIAETNLPVHYDLNGPRKLFANYKLPVHVRRSNFRLPSNPSTPVI MIGPGTGVAPFRGFIRERVAFLESQKKGGNNVSLGKHILFYGSRNTDDFLYQDEWPEYA KKLDGSFEMVVAHSRLPNTKKVYVQDKLKDYEDQVFEMINNGAFIYVCGDAKGMAK GVSTALVGILSRGKSITTDEATELIKMLKTSGRYQEDVW >CPR_3 Seq. ID NO: 65 MAAGDSHEDTSATVPEAVAEEVSLFSTTDIVLFSLIVGVLTYWFIFKKKKEEIPEFSKIQT TAPPVKESSFVEKMKKTGRNIIVFYGSQTGTAEEFANRLSKDAHRYGMRGMSADPEEY DLADLSSLPEIDKSLVVFCMATYGEGDPTDNAQDFYDWLQETDVDLTGVKFAVFGLGN KTYEHFNAMGKYVDQRLEQLGAQRIFELGLGDDDGNLEEDFITWREQFWPAVCEFFGV EATGEESSIRQYELVVHEDMDTAKVYTGEMGRLKSYENQKPPFDAKNPFLAAVTTNRK LNQGTERHLMHLELDISDSKIRYESGDHVAVYPANDSTLVNQIGEILGADLDVIMSLNNL DEESNKKHPFPCPTTYRTALTYYLDITNPPRTNVLYELAQYASEPSEQEHLHKMASSSGE GKELYLSWVVEARRHILAILQDYPSLRPPIDHLCELLPRLQARYYSIASSSKVHPNSVHIC AVAVEYEAKSGRVNKGVATSWLRTKEPAGENGRRALVPMFVRKSQFRLPFKPTTPVIM VGPGTGVAPFMGFIQERAWLREQGKEVGETLLYYGCRRSDEDYLYREELARFHKDGAL TQLNVAFSREQAHKVYVQHLLKRDKEHLWKLIHEGGAHIYVCGDARNMAKDVQNTFY DIVAEFGPMEHTQAVDYVKKLMTKGRYSLDVWS >CPR_4 Seq. ID NO: 66 MAAGDSHEDTSATMPEAVAEEVSLFSTTDMVLFSLIVGVLTYWFIFRKKKEEIPEFSKIQ TTAPPVKESSFVEKMKKTGRNIIVFYGSQTGTAEEFANRLSKDAHRYGMRGMSADPEEY DLADLSSLPEIDKSLVVFCMATYGEGDPTDNAQDFYDWLQETDVDLTGVKFAVFGLGN KTYEHFNAMGKYVDQRLEQLGAQRIFELGLGDDDGNLEEDFITWREQFWPAVCEFFGV EATGEESSIRQYELVVHEDMDAAKVYTGEMGRLKSYENQKPPFDAKNPFLAAVTANRK LNQGTERHLMHLELDISDSKIRYESGDHVAVYPANDSALVNQIGEILGADLDVIMSLNN LDEESNKKHPFPCPTTYRTALTYYLDITNPPRTNVLYELAQYASEPSEQEHLHKMASSSG EGKELYLSWVVEARRHILAILQDYPSLRPPIDHLCELLPRLQARYYSIASSSKVHPNSVHI CAVAVEYEAKSGRVNKGVATSWLRAKEPAGENGGRALVPMFVRKSQFRLPFKSTTPVI MVGPGTGIAPFMGFIQERAWLREQGKEVGETLLYYGCRRSDEDYLYREELARFHKDGA LTQLNVAFSREQAHKVYVQHLLKRDREHLWKLIHEGGAHIYVCGDARNMAKDVQNTF YDIVAEFGPMEHTQAVDYVKKLMTKGRYSLDVWS >CPR_5 Seq. ID NO: 67 MAAINMGDSHVDTSSTVSEAVAEEVSLFSMTDMILFSLIVGLLTYWFLFRKKKEEVPEFT KIQTLTSSVRESSFVEKMKKTGRNIIVFYGSQTGTAEEFANRLSKDAHRYGMRGMSADP EEYDLADLSSLPEIDNALVVFCMATYGEGDPTDNAQDFYDWLQETDVDLSGVKFAVFG LGNKTYEHFNAMGKYVDKRLEQLGAQRIFELGLGDDDGNLEEDFITWREQFWPAVCEH FGVEATGEESSIRQYELVVHTDIDAAKVYMGEMGRLKSYENQKPPFDAKNPFLAAVTT NRKLNQGTERHLMHLELDISDSKIRYESGDHVAVYPANDSALVNQLGKILGADLDIVMS LNNLDEESNKKHPFPCPTSYRTALTYYLDITNPPRTNVLYELAQYASEPSEQELLRKMAS SSGEGKELYLSWVVEARRHILAILQDCPSLRPPIDHLCELLPRLQARYYSIASSSKVHPNS VHICAVVVEYETKAGRINKGVATNWLRAKEPAGENGGRALVPMFVRKSQFRLPFKATT PVIMVGPGTGVAPFIGFIQERAWLRQQGKEVGETLLYYGCRRSDEDYLYREELAQFHRD GALTQLNVAFSREQSHKVYVQHLLKRDREHLWKLIEGGAHIYVCGDARNMARDVQNT FYDIVAELGAMEHAQAVDYIKKLMTKGRYSLDVWS >CPR_6 Seq. ID NO: 68 MAAINMGDSHMDTSSTVSEAVAEEVSLFSMTDMILFSLIVGLLTYWFLFRKKKEEVPEF TKIQTLTSSVRESSFVEKMKKTGRNIIVFYGSQTGTAEEFANRLSKDAHRYGMRGMSAD PEEYDLADLSSLPEIENALVVFCMATYGEGDPTDNAQDFYDWLQETDVDLSGVKFAVF GLGNKTYEHFNAMGKYVDKRLEQLGAQRIFELGLGDDDGNLEEDFITWREQFWPAVCE HFGVEATGEESSIRQYELVVHTDIDAAKVYMGEMGRLKSYENQKPPFDAKNPFLAAVT TNRKLNQGTERHLMHLELDISDSKIRYESGDHVAVYPANDSALVNQLGKILGADLDVV MSLNNLDEESNKKHPFPCPTSYRTALTYYLDITNPPRTNVLYELAQYASETSEQELLRK MASSSGEGKELYLSWVVEARRHILAILQDCPSLRPPIDHLCELLPRLQARYYSIASSSKVH PNSVHICAVVVEYETKAGRINKGVATNWLRAKEPAGENGGRALVPMFVRKSQFRLPFK ATTPVIMVGPGTGVAPFIGFIQERAWLRQQGKEVGETLLYYGCRRSDEDYLYREELVQF HRDGALTQLNVAFSREQSHKVYVQHLLKRDREHLWKLIEGGAHIYVCGDARNMARDV QNTFYDIVAELGAMEHTQAVDYIKKLMTKGRYSLDVWS >CPR_7 Seq. ID NO: 69 MAANMADSNMDAGTTTSEMVAEEVSLFSTTDVILFSLIVGVMTYWFLFRKKKEEVPEF TKIQTTTSSVKDRSFVEKMKKTGRNIIVFYGSQTGTAEEFANRLSKDAHRYGMRGMAA DPEEYDLADLSSLPEIEKALAIFCMATYGEGDPTDNAQDFYDWLQETDVDLSGVKYAVF ALGNKTYEHFNAMGKYVDKRLEQLGAQRIFDLGLGDDDGNLEEDFITWREQFWPAVC EHFGVEATGEESSIRQYELMVHTDMDMAKVYTGEMGRLKSYENQKPPFDAKNPFLAV VTTNRKLNQGTERHLMHLELDISDSKIRYESGDHVAVYPANDSALVNQLGEILGADLDII MSLNNLDEESNKKHPFPCPTSYRTALTYYLDITNPPRTNVLYELAQYASEPTEHEQLRK MASSSGEGKELYLRWVLEARRHILAILQDYPSLRPPIDHLCELLPRLQARYYSIASSSKVH PNSVHICAVAVEYETKTGRINKGVATSWLRAKEPAGENGGRALVPMYVRKSQFRLPFK ATTPVIMVGPGTGVAPFIGFIQERAWLRQQGKEVGETLLYYGCRRSDEDYLYREELAGF HKDGALTQLNVAFSREQPQKVYVQHLLKKDKEHLWKLIHEGGAHIYVCGDARNMARD VQNTFYDIVAEQGAMEHAQAVDYVKKLMTKGRYSLDVWS >CBNsyn_1 Seq. ID NO: 71 MAADFSGKNVWVTGAGKGIGYATALAFVEAGAKVTGFDQAFTQEQYPFATEVMDVA DAAQVAQVCQRLLAETERLDALVNAAGILRMGATDQLSKEDWQQTFAVNVGGAFNLF QQTMNQFRRQRGGAIVTVASDAAHTPRIGMSAYGASKAALKSLALSVGLELAGSGVRC NVVSPGSTDTDMQRTLWVSDDAEEQRIRGFGEQFKLGIPLGKIARPQEIANTILFLASDL ASHITLQDIVVDGGSTLGA >CBNsyn_2 Seq. ID NO: 72 MAASDLHNESIFITGGGSGLGLALVERFIEEGAQVATLELSAAKVASLRQRFGEHILAVE GNVTCYADYQRAVDQILTRSGKLDCFIGNAGIWDHNASLVNTPAETLETGFHELFNVNV LGYLLGAKACAPALIASEGSMIFTLSNAAWYPGGGGPLYTASKHAATGLIRQLAYELAP KVRVNGVGPCGMASDLRGPQALGQSETSIMQSLTPEKIAAILPLQFFPQPADFTGPYVML TSRRNNRALSGVMINADAGLAIRGIRHVAAGLDL >CBNsyn_3 Seq. ID NO: 73 MAATGWLAGKRALIVGAGSGIGRATVDAFLNEDARVAVLEYDSDKCATLRHQLPDVP VIEGDGTTRTANDEAVQVAVDAFGGLDTLVNCVGIFDFYRRIQDIPAELIDQAFDEMFRI NVLSHIHSVKAAVPALMGQDGASIVLTESASSFYPGRGGLLYVASKFAVRGVVTALAHE LAPRIRVNGVAPGGTLNTDLRGLDSLDLGARRLDAAPDRARELAARTPLGVALSGEDH AWSYVFLASHRSRGLTGETIHPDGGFSLGPPPQRN >CBNsyn_4 Seq. ID NO: 74 MSSIETKIFPGRFDGRCLTITGAAQGIGLTVATRIAAEGGEVVLVDRADLVHEVAEQLRE AGGKAHSVTADLETFEGAEEAISHAVRTTGRIDVLINVVGGTIWAKPYEHYAPEEIEKEI RRSLFPTLWTCRAAAPHLIERRAGTIVNVSSVATRGVNRVPYSAAKGGVNAITASLALE LAPYGVRVVATAPGGTVAPERRIARGPSPQSEQEKAWYQQIVDQTVDSSLLKRYGTLDE QAAAICFLASEEASYITGTVLPVAGGDLG >CBNsyn_5 Seq. ID NO: 75 MSSTGWLDGKRALVVGGGSGIGRAVVDAFLAEGACVAVLERDPNKCRVLREHLPQVP VIEGDATRAADNDAAVAAAVAAFGGLDTLVNCVGIFDFYQGIEDIPADTLDVAFDEMF RTNVLSHMHSVKAAVPELRKHRGSSIVLAESASSFYPGRGGVLYVSSKFAVRGLVTTLA YELAPDIRVNGVAPGGTLNTDLRGLASLGRDADRLDDNPNRANELAARTPLNVALSGE DHAWSFVFFASDRSRGITAGATHPDGGFGIGAPKPSTR >CBNsyn_6 Seq. ID NO: 76 MSSGFLDGKVALVTGGGSGIGRAVVELYVQQGAKVGILEISPEKVKDLRNALPADSVV VTEGDATSMADNERAVADVVDAFGPLTTLVCVVGVFDYFTEIPQLPKDKISEAFDQLFG VNVKSNLLSVKAALDELIENEGDIILTLSNAAFYAGGGGPLYVSSKFAVRGLVTELAYEL APKVRVNGVAPGGTITELRGIPALANEGQRLKDVPDIEGLIEGINPLGIVAQPEDHSWAY ALLASRERTSAVTGTIINSDGGLGVRGMTRMAGLAQ >CBNsyn_7 Seq. ID NO: 77 MSSSRSVTLVVGAAQGIGRATALTLATAGHRVVLADRDVDGLAETAALLHVAAPVHG LDVCDAAGVAEAVARVEVEHGPVDALAHVAGVFTTGSVLDSDLAEWQRMFDVNVTG LINVLRVVGHGMRERRRGAIVTVGSNSAGVPRVGMGAYGASKSAAHMLVRVLGLELA RFGVRANVVAPGSTDTAMQRSLWPDPADDAGARTAIDGDAASFKVGIPLGRIADPADIA DAVEFLLSDRARHITMQTLYVDGGATLRA >CBNsyn_8 Seq. ID NO: 78 MSSQMLDDHVALILGGGSGLGLGIARHFLGEGAQVAIFEISESKLLDLKAEFGDDVLLLQ GDVTSIDDLEAARAAVVDRFGRLDALIGAQGIFDGNIPLRDIPTERIEKVFDEVLHVDVL GYILAARVFLEELEKTDGAIVFTSSTAAYAADGGGLFYTAAKGAVRSVINQLAFEFAPK VRVNGVAPSGIANSQLQGPRALGLENNKQSDIPVEDFTNQFLSLTLTPTLPTPEEYAPLY AYLASRNNTTMTGQTIIADQGLFNRAVISNGVADRVGK >THCdeg_1 Seq. ID NO: 79 MSSSGPAHSNLEQVFANVASNYRGADVDLHAVYREMREKSPVLPENFMARLGVPSIAG LDPNRPTFTLFKYDDVMAVMRDATNFTSGFIAEGLGSFFDGLILTAMDGEAHKNIRSLL QPVFMPETVNRWKETKIDRVIREEYLRPMVASKRADIMEFALYFPIRVIYSLIGFPEDRPE EIEQYAAWALAILAGPQVDPEKAAAARGAAMEAAQALYDVVKVVVAQRRAEGATGD DLICRLIRAEYEGRSLDDHEITTFVRSLLPAASETTTRTFGTLMTLLLERPELLARIREDRS LVGKAIDEAVRYEPVATFKVRQAAKDVEIRGVAIPKGAMVSCIVTSANRDEDAFENADT FDIDRRAKPSFGFGFGPHMCIGQFVAKTEINCALNAILDLMPNIRLDPDKPAPEIIGAQLR GPHHVHVIWD >THCdeg_2 Seq. ID NO: 80 MSSRSTDLPDLKSAAFLADRYPTYRRLQSDFPHFEMNINGEECIVLTRYSDVDEVLRNPL ATVQQAPGVFPERIGQGAGARFYRESLPNIDAPDHTRIRRIVTPAFNPKTVANMRGWVE KVIVEHLDRLEGLDEIDFVSSFADPVPAEIACRLLHVPVSDAPELFARQHGLNAVLSVSDI TPERLAEADASAAFYYEYMDDVLNTLKGKLPEDDFVGALMAAEARDSGLTRSELVTTL IGFLVASYHTTKVAMTNTVLALLNHDGERARLVAQPDLARNAWEESLRYDSPVHFVHR YASEPLTIGGQPVAQGKRLLLGLHAASRDENRFAQADHYLIDRPDNRHLAFAGGGHFCL GSQLSRLEGDVLLRTIFQRFPAMRLTETRFERVPDLTFPMLLRMTVSLRAEQG >THCdeg_3 Seq. ID NO: 81 MSSTSNSIRSPLSPPQPRRTPPPCTSSREPPIVRGTWLLGSTRDLLRDPLELGLRGYAEGGD VVRYVVGLPGRRREFFTVNHPDGVGELLNAPRHLDYRKDSEFYRAMRDLYGNGLVTS QDETWLRQRRFIQPLFTPQSVDGYVTPMVAEADRVAIRWHNCTSRLVDLDGEMRALTL GVAARILFGVQAPRMLPILRTTLPVLGRAVLQQGASAIRFPSSWPTPGNRRIASAESRLD GLCDAIIERRRTVAEPGTDLLGRLVAAREDGDTLSTEEIRDQVKVFLLAGHDTTATMLTF ALYLLGKDAGVQDQARDEAERVLGAGTPTASDVHRLTYTTMVLEEAARLYPPSPYLTR RAVEESEVCGYRIPAGADVNLAPWVIHHRADLWPDPFRFDPDRFTPDRVKERHKYAWF PFGHGPRGCIGQRFAMLEAAVTLAILLREFEFRSPPGSVPLTVDLLLHPAGEVPCRVRRR VPVHSAVHRTHQPS >THCdeg_4 Seq. ID NO: 82 MSSAPDILSPEFLDNPYPLHRVLRDHYPALHHEGTDSYLISRYADCAEAFRSPKFSSRNY EWQLEPIHGRTILQMEGREHSTHRALLNPFFRGNGLERFMPAITHNAAQLIGDIVARNAG ELLGAVARQGEAELVSQFTSRFPINVMVDMLGLPKSDHERFRGWYFSIMAYLNNLAGD PEINAAAERTHVELREYMLPIIRERRSGDGDDLLSRLCRAEVDGEQMSDEEIKAFVSLLL VAGGETTDKAIASMIRNLIDHPDQMRAVREDRSLADRVIAETLRYSGPVHMIMRQTEDE VQIEDSTIPAGATCIMMLAAANRDERHFSNPDEFDIFRTDLNVDRAFSGAANHVQFILGR HFCVGSMLAKTEMTIALNLVLDTMDSIEYQDGFVPREEGLYTRSIPELRVKFEGKLG >THCdeg_5 Seq. ID NO: 83 MSSSTPAAATSLESAFAGVADNYKGSDVDLHAIYRDMRRNSPVIAEDFMARLGVPNIAG LDAKRPTFTLFKYKDVMSVLRDATNFTSGFIAEGLGAFFDGLILTGMDGEAHRRTRSLL QPVFMPDVVNRWRETKMAPIVRNEYIEPMVPKRRADLMDFGLHFPIRLIYSLIGFPDNRP EQIEQYAAWALAILAGPQVDAEKAAQARKAAMEAAQALYDAVKLEVTEVRKNGAQG DDLICRLIRAEYEGRHLDDHEVTTFVRSLLPAAGETTTRTFGSLMVALLERPELLERVRA DRSLVPKAIDEAVRFEPVATFKVRQAAQDTEIGGFSIPKGAMVQCIVSSANRDEEVFENS ESFDIDRKLKPSFGFGFGPHMCIGQFIAKVELSVAVNTILDLLPNLRLDPDRPKPRIVGAQ LRGPHALHVIWD >THCdeg_6 Seq. ID NO: 84 MSSSPSVAELSQELGEAFRLSSMDDPYPMLAERRRETPVMKGDIMVALGAPSYMGQHA GETHTVFRHDDVMAILRNHETFSSSIWEISQGPLIGRSILAMDGAEHRQWRGYLQSVFG GKLLSSWDESIFRPLAAKYVADLASKRGADLIAMALEYPLRAIYEILGLEDFKDNYEEFH ADVLTILLALWSTPDPAQADQFLLRFQKATEASARSWDRLLPIVQRKRAAGASRNDLIS SLIRAEYEGGVLDDEQITSFLRSLLLAATDTTTRQFLNTLTLLLQRPDELDRIRRDRSRLR LALAEGERLEPPALFIPRMITRDVVIRGTELTAGTPLLLAIGSANRDPEAYPPDPDEFRIDR TGPHHATFGFGTHICSGMNTTRREIAALIDAMLDGLPGLRVDPDAPAPLISGIHFRGPSAL PVVWD >THCdeg_7 Seq. ID NO: 85 MSSDYSRTPESLRPADSYAALSYSTVNAALRNDRVFSSKMYDSTIGVFMGPTILAMSGT KHRAHRNLVSAAFKPQSLRVWEPDIVRPICNALIDEFAGTGHADLVRDFTFEFPTRVIAR LLGLPAEDLPFFRKAAVAIISYAGNVPRALEASEDLKNYFLGHIEQRRSQPTDDIISDLVT AEVEGEQLTDEAIYSFLRLLLPAGLETTYRSSGNLLYLLLRHPRQFAAVQGNHGLIPQAV EEGLRYETPLTFVQRFTTEDTELGGVPVPAGAVVDLVLGSANRDEDRWERPGEFDIFRK PVPHISFTAGAHTCLGLHLARMETRVAVECLLTRLTNFRLQDEGDPHITGQPFRSPNLLP VTFDVV >THCdeg_8 Seq. ID NO: 86 MSSPTPRWRIPVLGDLLSVDPAKPVQKEMAMAAELGPLFERKIIGSRLTVVSGVDLVAE VNDEKHWARALGRPILKLRDVAGDGLFTAFNSEPAWARAHSVLGPGFSQSALRTYHGS MTRVLDDLVATWDDAAASGARVDVARDMTRLTFDVIGRAGFGRDFGSLRGDDLDPFA AAMGRALGYVNQTSNDIPLLRMVFGRGAAKRYQTDVAFMRDTVDELVASRAGRAERS DDLLDLMLHSADPDTGERLDMENIRNQVLTFLVAGNETTASTLAFALYFLAREPEVVER ARAEIADVVGDGEIAFEQVAKLRYVRRVVDETLRLWPAAPGYFRKVRHDTVLGGRYP MPKGSWVFVLLPQLHRDPVWGDDPERFDPDRFAPDAVRARPKDAYRPFGTGPRSCIGR QFALHEAVLALATLLRRYDVAPDPAYRLDIVEAVTLKPRGFELTLQRR >THCdeg_9 Seq. ID NO: 87 MSSSASSQSNLEQVFANVASNYRGADIDLHAVYREMREKSPVLPENFMARLGVPSIAGL DPDRPAFTLFKYDDVMAVMRDATNFTSGFIAEGLGSFFDGLILTAMDGEAHKNIRSLLQ PVFMPETVNRWKETKIDRVIREEYLQPMVASKGADIMEFALYFPIRVIYSLIGFPEDRPEE IEQYAAWALAILAGPQVDPEKAVAARGAAMEAAQALYDVVKVVVAQRRSQGATGDD LISRLIRAEYEGRSLDDHEITTFVRSLLPAASETTTRTFGTLMTLLLERPELLARIREDRSL VPKAIDEAVRYEPVATFKVRQAAKDVEIRGVAIPQGAMVSCIVTSANRDEDAFENADTF NIDRRAKPSFGFGFGPHMCIGQFVAKTEINCALNAILDLMPNIRLDPDKPAPEIIGAQLRG PHHVHVIWD >THCdeg_10 Seq. ID NO: 88 MSSTATELRDAPGSAPGLPRRSMLSLLPRMARDRLSVMTSVAARYGDAVTLPLGLSTLH FFNHPDYAKHVLADNSSNYHKGIGLIHAKRALGDGLLTSEGELWRKQRKTIQPAFAVKR LAGQAGAIAEEADRLVEHLLARQGRGPVDIRHEMTALTLGVLGRTLLDADLGAFGSVG HWFEAVQDQAMFDMMSLGTVPLWSPLPKQLRFRRARRELESVVDRLVAQRGDRPRAD GDDVVSRLVDSTGRERDPALRRKRMHDELVTLLLAGHETTASTLSWTFHLADEHPEVW ERLHAEAVEVLGDRRPVFEDLHRLRYTNRVLNEVMRLYPPVWLLPRRAVADDVVGGY RVPAGSDVLICPYTLHRHPEFWELPSRFDPDRFDPERSANRPRYAYIPFGAGPRFCVGNN LGLMEAAFVIAAIARRMRLRKVPGGTVVPEPMLTLRVRSGLPMTVHALDR >Oxid_1 Seq. ID NO: 89 MSSQRRDFLKYSVALGVASALPLWSRAVFAAERPTLPIPDLLTTDARNRIQLTIGAGQST FGGKTATTWGYNGNLLGPAVKLQRGKAVTVDIYNQLTEETTLHWHGLEVPGEVDGGP QGIIPPGGKRSVTLNVDQPAATCWFHPHQHGKTGRQVAMGLAGLVVIEDDEILKLMLP KQWGIDDVPVIVQDKKFSADGQIDYQLDVMTAAVGWFGDTLLTNGAIYPQHAAPRGW LRLRLLNGCNARSLNFATSDNRPLYVIASDGGLLPEPVKVSELPVLMGERFEVLVEVND NKPFDLVTLPVSQMGMAIAPFDKPHPVMRIQPIAISASGALPDTLSSLPALPSLEGLTVRK LQLSMDPMLDMMGMQMLMEKYGDQAMAGMDHSQMMGHMGHGNMNHMNHGGKF DFHHANKINGQAFDMNKPMFAAAKGQYERWVISGVGDMMLHPFHIHGTQFRILSENG KPPAAHRAGWKDTVKVEGNVSEVLVKFNHDAPKEHAYMAHCHLLEHEDTGMMLGFT V >Oxid_2 Seq. ID NO: 90 MSSRLSFLTSLVTLALVSSTYAGVGPVVDLTVSNAVISPDGFDRDAIVVNGVFPAPLITG KKGDRFQLNVIDNMTNHTMLKSTSIHWHGFFQKGTNWADGGAFVNQCPIAPGHSFLYD FRVPDQAGTFWYHSHLSTQYCDGLRGPIVVYDPNDPHADLYDVDNDSTVITLADWYH VAARLGPRFPLGADSTVINGLGRSLSTPNADLAVISVTQGKRYRFRLISLSCDPFHTFSID GHDLTIIEADSVNTEPLVVDAIPIFAGQRYSFVLSAVKDIDNYWIRADPNFGTTGFASGIN SAILRYDGAAPIEPTAVLAPVSVNPLVETDLHPLEDMPVPGRPTKGGVDKAINLDFSFSFP NFFINNATFTSPTVPILLQIMSGAQAAQDLLPSGSVIELPAQSTIELTLPATVNAPGVPHPF HLHGHTFAVVRSAGSTAYNYDNPIWRDVVSTGTPAANDNVTIRFTTDNPGPWFLHCHI DFHLEAGFAVVFAEGVPQTQVANPVPQAWEELCPIYDALPEDDQ >Oxid_3 Seq. ID NO: 91 MSSFKVSCKVTNNNGDQNVETNSVDRRNVLLGLGGLYGVANAIPLAASAAPTPPPDLK TCGKATISDGPLVGYTCCPPPMPTNFDNIPYYKFPSMTKLRIRSPAHAVDEEYIAKYNLAI SRMKDLDKTEPLNPLGFKQQANIHCAYCNGAYVFGDKVLQVHNSWLFFPFHRWYLYF YERILGKLIDDPTFALPYWNWDHPKGMRLPPMFDREGTSIYDERRNQQVRNGTVMDLG SFGDKVETTQLQLMSNNLTLMYRQMVTNAPCPLLFFGAPYVLGNNVEAPGTIENIPHIP VHIWAGTVRGSTFPNGDTSYGEDMGNFYSAGLDSVFYCHHGNVDRMWNEWKAIGGK RRDLSEKDWLNSEFFFYDENKKPYRVKVRDCLDAKKMGYDYAPMPTPWRNFKPKTKV SAGKVNTSSLPPVNEVFPLAKMDKVISFSINRPASSRTQQEKNEQEEMLTFDNIKYDNRG YIRFDVFLNVDNNVNANELDKVEFAGSYTSLPHVHRVGENDHTATVTFQLAITELLEDI GLEDEETIAVTLVPKKGGEGISIENVEIKLLDC >Oxid_4 Seq. ID NO: 92 MSGQNKMGLILVFLFLDGLLVCLAADVDVHNYTFVLQEKNFTKWCSTKSMLVVNGSF PGPTITARKGDTIFVNVINQGKYGLTIHWHGVKQPRNPWSDGPEYITQCPIKPGTNFIYEV ILSTEEGTLWWHAHSDWTRATVHGALVILPANGTTYPFPPPYQEQTIVLASWFKGDVME VITSSEETGVFPAAADGFTINGELGDLYNCSKETTYRLSVQPNKTYLLRIVNAVLNEEKF FGIAKHTLTVVAQDASYIKPINTSYIMITPGQTMDVLFTTDQTPSHYYMVASPFHDALDT FANFSTNAIIQYNGSYKAPKSPFVKPLPVYNDIKAADKFTGKLRSLANEKFPVNVPKVNV RRIFMAVSLNIVKCANKSCNNNIGHSTSASLNNISFALPQTDVLQAYYRNISGVFGRDFP TVQKKANFSLNTAQGTQVLMIEYGEAVEIVYQGTNLGAATSHPMHLHGFNFYLVGTGA GTFNNVTDPPKYNLVDPPELNTINLPRIGWAAIRFVADNPGVWFLHCHFERHTTEGMAT VVIVKDGGTTNTSMLPSPAYMPPCS >Oxid_5 Seq. ID NO: 93 MSSRKICLGCSHSLSSQPFTYTTQKTVSSRRIGDSQWRLSRGYTRTLTSASASVATAPAK LLTVNETQKCLRNMVRGGDVISYILSHSSRNADQNLKDLDSLILEPVCSATHEMFDVFEI PEHILTPFCDNRNVPEEQVTRNPNLRTDCLTMKRFVLLQSLVAVASAGIGPVADLYVGN RILAPDGFNRSTVLGGTSSSDFGFPAPLITGTKGDRFQLNVINQLTDTTMLRSTSIHWHGL FQAGSSWADGPVGVNQCPIAPGNSFLYDFNVPDQAGTFWYHSHYSTQYCDGLRGAFV VRDPNDPHASLYDVDNDDTVITLADWYHTSAKELSGSFPAEEATLINGLGRYSGGPTSP LAIVNVEAGKRYRFRLVSISCDPFYTFSIDGHDLTIIEADGENTDPLVVDYLEIYAGQRYS VVLNANQPVDNYWIRANSSNGPRDFVGGTNSAILRYAGASNSDPTTELGPRNNRLVEN NLHALGSPGVPGTHTIGEADVNINLEILFTPPNVLTVNGAQFIPPTAPVLLQILSGTKQAT DLLPPGSVYVLPRNAVVELTIPGGSGGSPHPMHLHGHVFDVVRSAGSDTINWDNPVRRD VVNIGTSTSDNATIRFTTDNPGPWIFHCHIDWHLEVGLAVVFAEDPDTIENSTHPAAWDE LCPIYDNLPSDEL >Oxid_6 Seq. ID NO: 94 MSSTLEKFVDALPIPDTLKPVQQSKEKTYYEVTMEECTHQLHRDLPPTRLWGYNGLFPG PTIEVKRNENVYVKWMNNLPSTHFLPIDHTIHHSDSQHEEPEVKTVVHLHGGVTPDDSD GYPEAWFSKDFEQTGPYFKREVYHYPNQQRGAILWYHDHAMALTRLNVYAGLVGAYII HDPKEKRLKLPSDEYDVPLLITDRTINEDGSLFYPSAPENPSPSLPNPSIVPAFCGETILVN GKVWPYLEVEPRKYRFRVINASNTRTYNLSLDNGGDFIQIGSDGGLLPRSVKLNSFSLAP AERYDIIIDFTAYEGESIILANSAGCGGDVNPETDANIMQFRVTKPLAQKDESRKPKYLAS YPSVQHERIQNIRTLKLAGTQDEYGRPVLLLNNKRWHDPVTETPKVGTTEIWSIINPTRG THPIHLHLVSFRVLDRRPFDIARYQESGELSYTGPAVPPPPSEKGWKDTIQAHAGEVLRIA ATFGPYSGRYVWHCHILEHEDYDMMRPMDITDPHK >Oxid_7 Seq. ID NO: 95 MSSVFSAAFSAFVALGLTLGAFAAVGPVADIHITDDTIAPDGFSRAAVLAGGTFPGPLIT GNMGDAFKLNVIDELTDASMLKSTSIHWHGFFQKGTNWADGPAFVNQCPITTGNSFLY DFQVPDQAGTYWYHSHLSTQYCDGLRGAFVVYDPSDPHKDLYDVDDESTVITLADWY HTLARQIVGVAISDTTLINGLGRNTDGPADAALAVINVEAGKRYRFRLVSISCDPNWVFS IDNHDFTVIEVDGVNSQPLNVDSVQIFAGQRYSLVLNANQPVDNYWIRADPNLGTTGFA GGINSAILRYKGAAVAEPTTSQTTSTKPLLETDLHPLVSTPVPGLPQPGGTDVVQNLILGF NAGQFTINGASFVPPTVPVLLQILSGTTNAQDLLPSGSVFELPLGKTVELTLAAGVLGGP HPFHLHGHNFHVVRSAGQDTPNYDDPIVRDVVSTGASGDNVTIRFTTDNPGPWFLHCHI DWHLEAGFAVVFAEAVNETKSGNPTPAAWDNLCTLYDALADGDK >Oxid_8 Seq. ID NO: 96 MSSCLAAIWSRKRAEHAASRLPALQEKRSTLSYAYARLDGSLASMFPNRFWSSVSLGAR IKPVDGSSEEPTARPSSCARPFLHSASSESGFVSSSRPTSFCVTCSRRWRCCSLLAMLGFR FLHTSVLAALTLSLKSYAAIGPVTDLTVANANISPDGYERAAVLAGGSFPGPLITGRKGD HFQINVVDQLTNHTMLKSTSIHWHGLFQKGTNWADGPAFVNQCPISTGNSFLYDFHVP DQAGTFWYHSHLSTQYCDGLRGAMVVYDPNDPHKNLYDVDNDDTVITLADWYHVAS KLGPAVPFGGDSTLINGKGRSTATPTADLAVISVTQGKRYRFRLVSLSCDPNFTFSIDGH ALTVIEADAVSTQPLTVDSIQIFAGQRYSFVLNANQSVDSYWIRAQPSLGNVGFDGGLNS AILRYDGAAPTEPSALAVPVSTNPLVETALRPLNSMPVPGKAEVGGVDKAINLAFSFNG TNFFINGATFVPPAVPVLLQIMSGAQSASDLLPSGSVFVLPSNATIELSFPATANAPGAPH PFHLHGHTFAVVRSAGSAEYNYENPIWRDVVSTGSPGDNVTIRFRTDNPGPWFLHCHID PHLEAGFAVVMAEDTRDVKADNPEPKAWDDLCPTYNALAVDDQ >Oxid_9 Seq. ID NO: 97 MFPGARILATLTLALHLLHGTNAAIGPTGDMYIVNEDVSPDGFTRSAVVARSDPTTNGT SETLTGVLVQGNKGDNFQLNVLNQLSDTTMLKTTSIHWHGFFQSGSTWADGPAFVNQC PIASGNSFLYDFNVPDQAGTFWYHSHLSTQYCDGLRGPFIVYDPSDPHLSLYDVDNADTI ITLEDWYHVVAPQNAVLPTADSTLINGKGRFAGGPTSALAVINVESNKRYRFRLISMSC DPNFTFSIDGHSLQVIEADAVNIVPIVVDSIQIFAGQRYSFVLNANQTVDNYWIRADPNLG STGFDGGINSAILRYAGATEDDPTTTSSTSTPLEETNLVPLENPGAPGPAVPGGADININL AMAFDVTNFELTINGSPFKAPTAPVLLQILSGATTAASLLPSGSIYSLEANKVVEISIPALA VGGPHPFHLHGHTFDVIRSAGSTTYNFDTPARRDVVNTGTDANDNVTIRFVTDNPGPWF LHCHIDWHLEIGLAVVFAEDVTSITAPPAAWDDLCPIYDALSDSDKDNPRFGFAPATGG KATGRRNWFSKARRRAILVPYLKLLKLGLVMVFYIRAERNHGRLSQSTPPNRRVDQREL ITNTWVERFFLHRLMFLKLFVGTACFMHIFNSVSSLGMCTLRTSHGSSESLASPSATMML GGGLTLLSANIRLWCYAEMRDLYDFEVNIKKAHRLVTTGPYSVSMVMFSKDHWLYQC GLRSMVGVVLSCIWCAEVVLINGIMVPARMKVEDDGLRRHFGREWDEYASRVAYRLV PEIY >Oxid_10 Seq. ID NO: 98 MSSKSFISAATLLVGILTPSVAAAPPSTPEQRDLLVPITEREEAAVKARQQSCNTPSNRAC WTDGYDINTDYEVDSPDTGVVRPYTLTLTEVDNWTGPDGVVKEKVMLVNNSIIGPTIFA DWGDTIQVTVINNLETNGTSIHWHGLHQKGTNLHDGANGITECPIPPKGGRKVYRFKAQ QYGTSWYHSHFSAQYGNGVVGAIQINGPASLPYDTDLGVFPISDYYYSSADELVELTKN SGAPFSDNVLFNGTAKHPETGEGEYANVTLTPGRRHRLRLINTSVENHFQVSLVNHTMT IIAADMVPVNAMTVDSLFLGVGQRYDVVIEASRTPGNYWFNVTFGGGLLCGGSRNPYP AAIFHYAGAPGGPPTDEGKAPVDHNCLDLPNLKPVVARDVPLSGFAKRPDNTLDVTLD TTGTPLFVWKVNGSAINIDWGRPVVDYVLTQNTSFPPGYNIVEVNGADQWSYWLIEND PGAPFTLPHPMHLHGHDFYVLGRSPDESPASNERHVFDPARDAGLLSGANPVRRDVTM LPAFGWVVLAFRADNPGAWLFHCHIAWHVSGGLGVVYLERADDLRGAVSDADADDL DRLCADWRRYWPTNPYPKSDSGL >Oxid_11 Seq. ID NO: 99 MSSRFQSLFFFVLVSLTAVANAAIGPVADLTLTNAQVSPDGFAREAVVVNGITPAPLITG NKGDRFQLNVIDQLTNHTMLKTSSIHWHGFFQQGTNWADGPAFVNQCPIASGHSFLYD FQVPDQAGTFWYHSHLSTQYCDGLRGPFVVYDPNDPHASLYDIDNDDTVITLADWYHV AAKLGPRFPFGSDSTLINGLGRTTGIAPSDLAVIKVTQGKRYRFRLVSLSCDPNHTFSIDN HTMTIIEADSINTQPLEVDSIQIFAAQRYSFVLDASQPVDNYWIRANPAFGNTGFAGGINS AILRYDGAPEIEPTSVQTTPTKPLNEVDLHPLSPMPVPGSPEPGGVDKPLNLVFNFNGTNF FINDHTFVPPSVPVLLQILSGAQAAQDLVPEGSVFVLPSNSSIEISFPATANAPGFPHPFHL HGHAFAVVRSAGSSVYNYDNPIFRDVVSTGQPGDNVTIRFETNNPGPWFLHCHIDFHLD AGFAVVMAEDTPDTKAANPVPQAWSDLCPIYDALDPSDL >Oxid_12 Seq. ID NO: 100 MSSGLQRFSFFVTLALVARSLAAIGPVASLVVANAPVSPDGFLRDAIVVNGVVPSPLITG KKGDRFQLNVDDTLTNHSMLKSTSIHWHGFFQAGTNWADGPAFVNQCPIASGHSFLYD FHVPDQAGTFWYHSHLSTQYCDGLRGPFVVYDPKDPHASRYDVDNESTVITLTDWYHT AARLGPRFPLGADATLINGLGRSASTPTAALAVINVQHGKRYRFRLVSISCDPNYTFSID GHNLTVIEVDGINSQPLLVDSIQIFAAQRYSFVLNANQTVGNYWVRANPNFGTVGFAGG INSAILRYQGAPVAEPTTTQTTSVIPLIETNLHPLARMPVPGSPTPGGVDKALNLAFNFNG TNFFINNATFTPPTVPVLLQILSGAQTAQDLLPAGSVYPLPAHSTIEITLPATALAPGAPHP FHLHGHAFAVVRSAGSTTYNYNDPIFRDVVSTGTPAAGDNVTIRFQTDNPGPWFLHCHI DFHLDAGFAIVFAEDVADVKAANPVPKAWSDLCPIYDGLSEANQ >MBP Seq. ID NO: 101 ATGAAGATTGAGGAGGGAAAACTTGTCATATGGATTAATGGCGACAAAGGCTATAA TGGGTTAGCAGAAGTCGGTAAAAAGTTTGAGAAAGACACTGGGATTAAGGTAACGG TCGAGCACCCAGATAAGCTGGAAGAGAAATTCCCACAGGTTGCCGCGACTGGGGAT GGCCCCGACATCATATTCTGGGCGCACGACAGATTTGGCGGTTATGCACAAAGTGG GTTACTAGCTGAAATTACCCCAGATAAGGCATTTCAAGACAAACTATATCCTTTCAC TTGGGATGCGGTTAGATATAACGGAAAATTGATAGCCTATCCTATTGCCGTGGAGGC TTTATCACTAATCTATAACAAGGACCTATTGCCGAACCCGCCCAAAACATGGGAAGA AATCCCTGCCTTAGACAAAGAACTTAAAGCGAAAGGCAAGAGTGCTCTAATGTTCA ATCTTCAAGAGCCTTATTTTACTTGGCCCTTGATAGCGGCCGATGGCGGCTACGCCTT CAAGTACGAGAACGGGAAGTATGATATTAAAGACGTTGGAGTGGATAACGCGGGTG CGAAGGCTGGCCTGACGTTCTTAGTGGACTTGATTAAAAATAAGCACATGAACGCG GACACGGACTACAGCATCGCGGAGGCGGCTTTTAATAAGGGCGAAACTGCTATGAC GATCAATGGACCTTGGGCTTGGTCAAATATAGATACAAGTAAGGTAAATTATGGAG TAACTGTGCTGCCGACCTTTAAGGGCCAACCTAGTAAACCGTTTGTCGGCGTGTTGT CCGCCGGGATAAACGCCGCCTCCCCCAACAAAGAATTAGCAAAGGAATTTTTGGAG AATTACTTACTGACCGATGAGGGCTTGGAGGCAGTCAATAAGGATAAGCCCCTGGG CGCTGTCGCATTGAAGTCATATGAAGAAGAACTTGCAAAAGATCCCCGTATTGCTGC CACAATGGAGAATGCACAGAAAGGTGAAATAATGCCCAACATACCGCAGATGAGTG CGTTCTGGTATGCGGTAAGAACAGCTGTTATCAACGCTGCGTCCGGGAGGCAAACA GTTGATGAGGCTTTGAAAGACGCTCAGACCAATTCCTCCAGCAACAACAATAATAAT AACAATAACAACAACTTAGGTATAGAAGGTAGATAA >VEN Seq. ID NO: 102 ATGGTTAGTAAAGGAGAAGAGTTATTCACTGGCGTTGTACCTATTCTGGTTGAGCTA GACGGAGATGTTAATGGCCACAAATTCTCCGTATCCGGGGAGGGGGAGGGCGATGC AACATATGGAAAACTTACGCTAAAACTAATCTGTACGACTGGGAAACTACCCGTTCC GTGGCCCACATTGGTTACGACACTTGGCTATGGCCTACAGTGTTTCGCTAGATACCC TGATCATATGAAGCAACATGATTTCTTTAAGAGTGCAATGCCGGAGGGTTACGTTCA GGAAAGAACAATTTTCTTCAAGGATGACGGCAATTACAAGACGAGGGCCGAGGTAA AATTCGAGGGGGATACGCTGGTTAACAGGATAGAATTAAAAGGTATAGATTTTAAA GAAGACGGGAACATTCTAGGTCATAAACTTGAGTACAATTACAACTCCCATAATGTC TACATAACAGCGGACAAGCAGAAGAATGGTATAAAGGCAAATTTTAAGATCAGACA TAACATTGAAGACGGGGGAGTCCAGTTGGCTGACCACTATCAACAAAATACCCCCA TTGGGGACGGTCCGGTGTTGCTTCCAGATAACCACTATCTTTCTTACCAGTCAGCCCT ATCCAAAGACCCAAACGAGAAGAGGGATCATATGGTTCTTCTGGAGTTTGTCACCGC AGCAGGGATTACTTTGGGGATGGACGAGCTATACAAGTAA >MST Seq. ID NO: 103 ATGGCTATGTTCTGCACTTTCTTCGAAAAACATCATCGTAAATGGGACATTTTACTA GAGAAATCCACCGGTGTGATGGAGGCGATGAAAGTGACATCCGAAGAAAAGGAAC AACTGAGCACAGCTATTGACCGTATGAACGAGGGCCTGGATGCTTTTATCCAGCTAT ATAACGAGTCCGAAATAGACGAGCCCCTTATCCAGCTTGACGATGACACAGCCGAA TTAATGAAACAAGCTAGAGATATGTACGGTCAGGAGAAGTTAAATGAAAAACTAAA TACAATCATTAAGCAAATTTTGTCAATCTCTGTATCCGAGGAGGGAGAGAAAGAAG GCAGCGGATCAGGATAA >OSP Seq. ID NO: 104 ATGTATCTTCTAGGGATTGGGCTTATTTTAGCACTGATTGCCTGCAAGCAAAACGTTT CTTCACTAGACGAGAAAAACTCAGTGTCAGTAGACCTTCCTGGTGAGATGAAGGTTT TGGTCAGCAAGGAAAAGAACAAAGATGGCAAGTACGATTTAATTGCTACCGTGGAT AAGTTGGAGCTGAAAGGAACATCCGACAAGAACAACGGCTCTGGGGTACTTGAAGG AGTCAAGGCCGATAAAAGCAAAGTCAAGCTAACAATTTCCGACGACGGGTCTGGAT AA >OLE Seq. ID NO: 105 ATGGCAGACAGAGATAGGTCAGGTATCTATGGCGGTGCTCATGCGACGTATGGCCA ACAGCAACAGCAAGGAGGAGGCGGGAGACCTATGGGCGAACAAGTCAAGGGCATG CTGCATGACAAGGGCCCTACGGCGTCCCAGGCCTTGACAGTTGCTACCTTATTTCCT TTAGGAGGGCTGCTTTTGGTGCTTAGTGGATTAGCCCTTACTGCTTCCGTAGTCGGTC TAGCAGTCGCAACGCCGGTCTTTTTGATCTTCAGTCCGGTGCTAGTCCCAGCGGCAT TGCTAATCGGCACTGCCGTCATGGGGTTCTTGACCTCCGGTGCTCTGGGTCTGGGTG GTTTGTCCTCTCTGACCTGTCTAGCAAACACTGCGCGTCAGGCTTTTCAGCGTACCCC TGACTACGTGGAAGAAGCTCATAGAAGGATGGCTGAGGCAGCAGCGCATGCCGGAC ATAAGACGGCTCAGGCTGGGCAAGCTATTCAAGGCAGGGCTCAAGAGGCTGGCGCT GGTGGTGGGGCCGGGTAA >MBP Seq. ID NO: 106 MSKIEEGKLVIWINGDKGYNGLAEVGKKFEKDTGIKVTVEHPDKLEEKFPQVAATGDGP DIIFWAHDRFGGYAQSGLLAEITPDKAFQDKLYPFTWDAVRYNGKLIAYPIAVEALSLIY NKDLLPNPPKTWEEIPALDKELKAKGKSALMFNLQEPYFTWPLIAADGGYAFKYENGK YDIKDVGVDNAGAKAGLTFLVDLIKNKHMNADTDYSIAEAAFNKGETAMTINGPWAW SNIDTSKVNYGVTVLPTFKGQPSKPFVGVLSAGINAASPNKELAKEFLENYLLTDEGLEA VNKDKPLGAVALKSYEEELAKDPRIAATMENAQKGEIMPNIPQMSAFWYAVRTAVINA ASGRQTVDEALKDAQTNSSSNNNNNNNNNNLGIEGR >VEN Seq. ID NO: 107 MVSKGEELFTGVVPILVELDGDVNGHKFSVSGEGEGDATYGKLTLKLICTTGKLPVPWP TLVTTLGYGLQCFARYPDHMKQHDFFKSAMPEGYVQERTIFFKDDGNYKTRAEVKFEG DTLVNRIELKGIDFKEDGNILGHKLEYNYNSHNVYITADKQKNGIKANFKIRHNIEDGGV QLADHYQQNTPIGDGPVLLPDNHYLSYQSALSKDPNEKRDHMVLLEFVTAAGITLGMD ELYK >MST Seq. ID NO: 108 MSAMFCTFFEKHHRKWDILLEKSTGVMEAMKVTSEEKEQLSTAIDRMNEGLDAFIQLY NESEIDEPLIQLDDDTAELMKQARDMYGQEKLNEKLNTIIKQILSISVSEEGEKEGSGSG >OSP Seq. ID NO: 109 MSSYLLGIGLILALIACKQNVSSLDEKNSVSVDLPGEMKVLVSKEKNKDGKYDLIATVD KLELKGTSDKNNGSGVLEGVKADKSKVKLTISDDGSG >OLE Seq. ID NO: 110 MSSADRDRSGIYGGAHATYGQQQQQGGGGRPMGEQVKGMLHDKGPTASQALTVATL FPLGGLLLVLSGLALTASVVGLAVATPVFLIFSPVLVPAALLIGTAVMGFLTSGALGLGG LSSLTCLANTARQAFQRTPDYVEEAHRRMAEAAAHAGHKTAQAGQAIQGRAQEAGAG GGAG