BACTERIUM COMPRISING MYO-INOSITOL TO PROPIONATE PATHWAY

Abstract

The invention is concerned with a bacterium comprising a inositol to propionic acid pathway gene set that allows said bacterium to convert inositol to propionic acid or a salt or ester thereof. The bacterium can be used as a probiotic or supplement to promote production of propionic acid in the GI tract, thereby preventing and/or treating conditions or diseases that benefit from the production of propionic acid, for example metabolic disease, metabolic syndrome, insulin resistance or insulin resistance-related conditions, particularly dyslipidemia, type 2 diabetes mellitus and insulin-resistance in endocrine diseases.

Claims

1. Bacterium comprising a gene set that allows said bacterium to convert inositol to propionic acid or a salt or ester thereof, for use in preventing and/or treating metabolic syndrome, insulin resistance or insulin resistance-related condition, wherein the gene set comprises genes encoding one or more of the proteins: myo-inositol 2-dehydrogenase, inosose dehydratase, epi-inositol hydrolase, 5-deoxy-glucuronate isomerase, 5-keto-2-deoxygluconokinase, 5-keto-2-deoxy-D-gluconate-6 phosphate aldolase, glyceraldehyde-3-phosphate ketol-isomerase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, phosphoglycerate mutase, enolase, pyruvate kinase, pyruvate-flavodoxin oxidoreductase, 3-oxoacid CoA transferase. acyl-CoA dehydrogenase, enoyl-CoA hydratase, acryloyl-CoA dehydrogenase/Etf, and inosose isomerase.

2. The bacterium for use according to claim 1, wherein at least one of the genes encoding any one or more of the proteins: myo-inositol 2-dehydrogenase, inosose dehydratase, epi-inositol hydrolase, 5-deoxy-glucuronate isomerase, 5-keto-2-deoxygluconokinase, 5-keto-2-deoxy-D-gluconate-6 phosphate aldolase, glyceraldehyde-3-phosphate keto-isomerase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, phosphoglycerate mutase, enolase, pyruvate kinase, pyruvate-flavodoxin oxidoreductase, 3-oxoacid CoA transferase. acyl-CoA dehydrogenase, enoyl-CoA hydratase, acryloyl-CoA dehydrogenase/Etf, and inosose isomerase, is overexpressed when the bacterium is grown in the presence of inositol as compared to when the bacterium is grown in the absence of inositol.

3. The bacterium for use according to claim 1, wherein the use is in preventing and/or treating insulin resistance or insulin resistance-related condition.

4. The bacterium for use according to claim 3, wherein the insulin resistance-related condition is chosen from dyslipidemia, type 2 diabetes mellitus and insulin-resistance in endocrine disease.

5. The bacterium for use according to claim 1, wherein the bacterium is a human intestinal isolate bacterium.

6. The bacterium for use according to claim 1, wherein the bacterium is deposited as CBS 140182.

7. The bacterium for use according to claim 1, wherein the bacterium is comprised in a composition further comprising a physiologically acceptable carrier.

8. The bacterium for use according to claim 7, wherein the composition is a food composition.

9. The bacterium for use according to claim 7, wherein the composition is a pharmaceutical composition.

10. The bacterium for use according to claim 7, wherein in the composition the bacterium is present in lyophilized or microencapsulated form.

11. The bacterium for use according to claim 1, wherein the bacterium is present in an amount within the range of between 10.sup.6 to 10.sup.15 colony forming units (CFU).

12. The bacterium for use according to claim 1, wherein the bacterium is administered separately, sequentially or simultaneously with inositol.

13. The bacterium for use according to claim 1 for use as a probiotic.

14. The bacterium for use according to claim 2, wherein the use is in preventing and/or treating insulin resistance or insulin resistance-related condition.

15. The bacterium for use according to claim 14, wherein the insulin resistance-related condition is chosen from dyslipidemia, type 2 diabetes mellitus and insulin-resistance in endocrine disease.

16. The bacterium for use according to claim 2, wherein the bacterium is a human intestinal isolate bacterium.

17. The bacterium for use according to claim 2, wherein the bacterium is deposited as CBS 140182.

18. The bacterium for use according to claim 2, wherein the bacterium is comprised in a composition further comprising a physiologically acceptable carrier.

19. The bacterium for use according to claim 8, wherein the food composition is a dairy product.

20. The bacterium for use according to claim 9, wherein the composition is a pharmaceutical composition in solid dosage form.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0112] FIG. 1. A bacterium according to the present disclosure is able to ferment efficiently myo-inositol to propionate. The experiment was performed twice.

[0113] FIGS. 2A/2B. the identified inositol to propionate pathway.

[0114] FIG. 3A/3B. shows the capabilities of metabolizing myo-inositol by different Anaerostipes strains

[0115] FIG. 4. the presence of inositol pathway genes in NCO genomes of Anaerostipes isolates

[0116]

TABLE-US-00001 Sequence listing Myo-inositol 2-dehydrogenase 1 - AR1Y2_0317 Nucleotide sequence (SEQ ID NO: 1) atggtaaatgtaggtattatcggagcaggaagaatcggaagagtacatgtagaaagcatctgcacacaggtaggaaacgca aaggttaagactcttgctgatccttttatgtcagaggacacagcagtatgggcaaaagaaatgggtgttgaaaataccaccaaa gattacaaagacatcttaaatgatcctcagatcgacgcagtgctgatctgctcatccacagatacacattcaccgatctccgtag aggctattgaagcaggaaaacatgtattctgcgaaaagccaatcgaccatgacgtacagaagattcaggaagtagtcgacg ctttaaagaaaagcgacgtaaaataccaggtaggattcaaccgccgttttgaccataactttgaagccatccgggatgccgtgg ctgctggaaagattggtgagacacagatcatcaaagttacatccagagatcctgaaccgccaagtgctgattatgtaaaagttt ccggaggaatgttcctggacatgacaatccatgattttgacatggtccgtttccttgcaggatgtgacgctgaagaagtgtatgta gaagctgcagtccttgtagatcctgccatcggtgaagccggagatgtggacactgctgttatcacattaaaaatgaaaaacggt tccatcgccgtgattgacaactcaagaaaagccgtttacggatacgatcagagagctgaagtgttcggatcaaagggaatggt cgtaacagcaaacgattccgcatcctcagccgtgatcagtaatgcggacggagtgacaggagaaaaacctctttacttcttcct ggaacgctacatggcagcctatgcaaaagaaatcaaatgctttatcgacgccatcgaaaaaaacacagacacccctcttgg agttatggacggtcttgagccagtacttatggggcttgcggctaaaaaatcattagaagaacaccgcccagtaaaaatttctga aattacagtatag Amino acid sequence (SEQ ID NO: 2) MVNVGIIGAGRIGRVHVESICTQVGNAKVKTLADPFMSEDTAVWAKEMGVENTTKDYKDIL NDPQIDAVLICSSTDTHSPISVEAIEAGKHVFCEKPIDHDVQKIQEVVDALKKSDVKYQVGF NRRFDHNFEAIRDAVAAGKIGETQIIKVTSRDPEPPSADYVKVSGGMFLDMTIHDFDMVRF LAGCDAEEVYVEAAVLVDPAIGEAGDVDTAVITLKMKNGSIAVIDNSRKAVYGYDQRAEVF GSKGMVVTANDSASSAVISNADGVTGEKPLYFFLERYMAAYAKEIKCFIDAIEKNTDTPLGV MDGLEPVLMGLAAKKSLEEHRPVKISEITV Myo-inositol 2-dehydrogenase 2 - AR1Y2_0342 Nucleotide sequence (SEQ ID NO: 3) atgaacaaagtaagagtaggtattgctggtttaggaagattagggaaattacatgcagagaatatcgcattcaagattccaaac gcggaacttacagcggcctgttcgatcgcgccagaggaattggaatatgccacagaacatttcggggtaaccgatgtttataca gatttttatgagatgttagataaagcagacattgatgtcgtggcggtggtgaccacgagcggagaacactgctggcagatcaaa gcagcattggacgctggaaaacatgttttttgcgataaacctctcggggttacggtcaatgaatgtaaaacagcggaggccgc ggtggaacgccacccagagcttacattttttcttggatttatgcgccgttatgacccatcctacgcttatgcgaaaaagaaaatcc aggagggagccattggtaagccgtatatggtaaaagcggcagggatcgacccggaagctctggtggagggagcagtaaaa tttgcagccaccagcggcggtatttttatcgacatggcaatccatgatatcgatttaatgcgctggcttttggaatccgatccggtgg aagtctacgctgcaggggccacgtttaaacatcccgaattcagggaggcaggggatgacgagacgggggcagccatgtac aaatgtgagaacggtgcactgggatttgtacatgttgggcgtacagcggcccatggatatcatgtggagacagagatcatcgg aacagagggaagcctgagaatcagtcctgtaccggaaaagaacctgtgtatgatctacgatgagaacggagctgtgacaga atgtgtcagcggttttgcagaacggtttgcagaggcatacctgttggaaatgaaggaattcatcaactgtgtccagagcggcac aaagccggatgtgaccgtatatgacggcacaaaatccacacagatcggttttgccacaacagaagcgtggaaaaagggctg tactgcaaagatccagtactag Amino acid sequence (SEQ ID NO: 4) MNKVRVGIAGLGRLGKLHAENIAFKIPNAELTAACSIAPEELEYATEHFGVTDVYTDFYEML DKADIDVVAVVTTSGEHCWQIKAALDAGKHVFCDKPLGVTVNECKTAEAAVERHPELTFFL GFMRRYDPSYAYAKKKIQEGAIGKPYMVKAAGIDPEALVEGAVKFAATSGGIFIDMAIHDID LMRWLLESDPVEVYAAGATFKHPEFREAGDDETGAAMYKCENGALGFVHVGRTAAHGY HVETEIIGTEGSLRISPVPEKNLCMIYDENGAVTECVSGFAERFAEAYLLEMKEFINCVQSG TKPDVTVYDGTKSTQIGFATTEAWKKGCTAKIQY Inosose dehydratase - AR1Y2_0345 Nucleotide sequence (SEQ ID NO: 5) atgtttaacaaagaaaaagtaaaattaggaattgccccgatcgcttggaccaacgatgatcttccggatcttggaaaagaaaa cacctttgagcagtgtgtcagtgaaatggcattggcagggtacactggttccgaagtaggaaataaatatccaaaggacccag aggttctaaaaaaggccctgaaactccggggaatggagatctgcaatcagtggttctcatcatttttgatcacaaagccatttga agaggtggaaaaagagttccgcgctcaactgagtttcttaaaggctgtgggagcaaagatcattggtgcttctgaacagagcc acagtgtacagggtatgctggatactccgatctttggacataagtatgtgatgaatgacgaagagtgggaaaccttctgtacggg aatgaataagttaggaaaaatcgcaaaagaagaatacggcatcagcttaaccttccaccatcatatgggaactgtggtacag gacccggatgaagtggaaagaatgatggcaaacacagatcctgaatatgtgaatctgttatttgatacagggcattttacatact gcggggcagatcctcttgaaatggtgaaaaaatatgtggaccgcatcaaacatgtccatcttaaggatatccgtccggaaatcg tagaaaaagtgaaagcagaaaacttaagcttcttagatggtgtgcgtatgggggcgtttacggtaccgggtgacggatgtattg attttgatccgatctttaaggtgcttgaagattcaggatatgaaggatatatgctggtagaggcagaacaggatccggccaaggc aaatccgcttgaatatgccatgaaggcaagaaaattcatcgctgagaaaactggattataa Amino acid sequence (SEQ ID NO: 6) MFNKEKVKLGIAPIAWTNDDLPDLGKENTFEQCVSEMALAGYTGSEVGNKYPKDPEVLKK ALKLRGMEICNQWFSSFLITKPFEEVEKEFRAQLSFLKAVGAKIIGASEQSHSVQGMLDTPI FGHKYVMNDEEWETFCTGMNKLGKIAKEEYGISLTFHHHMGTVVQDPDEVERMMANTDP EYVNLLFDTGHFTYCGADPLEMVKKYVDRIKHVHLKDIRPEIVEKVKAENLSFLDGVRMGA FTVPGDGCIDFDPIFKVLEDSGYEGYMLVEAEQDPAKANPLEYAMKARKFIAEKTGL Epi-inositol hydrolase - AR1Y2_1105 Nucleotide sequence (SEQ ID NO: 7) atgagtacaaccagaatgacagtagcacaggctcttgtaaaattccttgacaatcagtatgtggaatttgacggggaagaaac aaaatttgtagaaggtttctttactatcttcggacacgggatcgccgttggtctcggagaggcattggacagcaatcctgggagct taaaggttcttcagggaagaaatgagcagggaatgtgccacgtagcgacagcttacgcaaaacaaaatagaagaaggaa gatcattccttgtgcatcttctgtaggacccggagcggcaaatatggtgacagcagcggctacagctacagtgaacaatattcc gcttttggtagtgccttctgacacatttgccacaagacagccggacccggtgctccagcagttagaaaagagtgacagtctctct acaacaacaaacgacgcattcaaaccggtttgtaaatattgggataggatcatccgcccggaacagctgatgacagccatgg tcaacgctatgcgtgttctcacagatccgtcagagacaggcgctgtgtgcattgcactctcccaggatgtagaaggagaatctta tgatttccctgactatctgtttgaaaaacgtgtacataggatcacaagaccttgcgcggtaaaagaagagatcgaggaccttgta aaagtcattaaagaagcgaaaaatccgttagtgatcgtgggcggaggtgtgaagtattctgaggcaggagaagctgtagaaa agttctgcgaagactttaacatcccgttcggagagagccaggcaggaaaaagtgcctgcaagtcaagccacccttactgctta ggaggaatcggcgtcacaggaaccctggctgccaataccatcgctgatgaagctgatgtggtcattgcagtgggaaccagac tttcagactttacaacaggatctaaaggacagttcaaaaatcctaatgtaaaaatggtgacgatcaacaacaataaatatcatg catataaaatggatgcagtaaaagctgtcggagacgcgaaagtgacagtggaagctctttctgctagactgaaagaggaag gatacaagtctgcttacacaacagagatccaggacgcaaaggcagcctgggataaagaaatggaccgccttgcgaatattg agtatacaggcgatgactttgagccggagatcaaagcgagagatccgcgtacgattcctgaattcgtaaaacttacaggggg acttatcactcagactgcagcattgtgcaaaatccgtgaggtcattgatgaagacgctaatattgtgacagcaggggggagtctt ccaagctgtatgcagagaatctggaccacagacaaacgaggcggatatcacgcagaatacggatattcctgcatgggatatg aagtggcgggagcgctcggcgtaaagatggcagagcctgagcatgaatcctacgtggttgtgggggatgccagctttcagat gctccacagtgagattatgacagcgatgcaggaaaaacaaaagatcaacatccttgtatttgacaactgcggatttggctgtat caacaaccttcagatgaatcatggagtgggaagtcttgcaacagagttcagataccgcgatgaaaacaatgagatcaagggt gatctgatcccggttgactatgcaaaagtcggagaaggatacggactcaagacgtacagtgtaagaacgatcaaagagctg gaggaagcattgatcgatgctaagaaacaggacgttgccacattgatcgacttgaaggtcattccgaaaacaatgacagacg gttacaaatcatggtggaacgtaggtattgcgacaacttctgtgaaagaaagcgtgcagaaagcatgtgaaggagtattggaa ggccgcaaaaacgcaagacagtattag Amino acid sequence (SEQ ID NO: 8) MSTTRMTVAQALVKFLDNQYVEFDGEETKFVEGFFTIFGHGIAVGLGEALDSNPGSLKVLQ GRNEQGMCHVATAYAKQNRRRKIIPCASSVGPGAANMVTAAATATVNNIPLLVVPSDTFA TRQPDPVLQQLEKSDSLSTTTNDAFKPVCKYWDRIIRPEQLMTAMVNAMRVLTDPSETGA VCIALSQDVEGESYDFPDYLFEKRVHRITRPCAVKEEIEDLVKVIKEAKNPLVIVGGGVKYS EAGEAVEKFCEDFNIPFGESQAGKSACKSSHPYCLGGIGVTGTLAANTIADEADVVIAVGT RLSDFTTGSKGQFKNPNVKMVTINNNKYHAYKMDAVKAVGDAKVTVEALSARLKEEGYKS AYTTEIQDAKAAWDKEMDRLANIEYTGDDFEPEIKARDPRTIPEFVKLTGGLITQTAALCKIR EVIDEDANIVTAGGSLPSCMQRIWTTDKRGGYHAEYGYSCMGYEVAGALGVKMAEPEHE SYVVVGDASFQMLHSEIMTAMQEKQKINILVFDNCGFGCINNLQMNHGVGSLATEFRYRD ENNEIKGDLIPVDYAKVGEGYGLKTYSVRTIKELEEALIDAKKQDVATLIDLKVIPKTMTDGY KSVWVNVGIATTSVKESVQKACEGVLEGRKNARQY 5-deoxy-glucuronate isomerase - AR1Y2_1106 Nucleotide sequence (SEQ ID NO: 9) atgggtaaagtattcggctatcctgagtttgatgtaaacggggaaaaggttttaacaacatatgacaatgattataaagaaatgct gatggacatccgcgtcttccgcttaaaagcgggagatgtgaagaccttctgcaaagaaaaagaggagaccgcggttcttttact aaaaggggatgtcgtattctcatttgatgaaacttccaaagaagtcacaagaaaagatgtatttacagaaggaccttgggcagt acatatctgcacaggagccaaagtcatagtggaagcaaaggcagactctgaaatcttggtacagtccacaatgaatgaccag acatttgagagtaaattgtatgcgccggaagatgctccttggggatattcctgtgtaggaaagttcggaaatgtggctaaacgcc gtgtcaataccatctttgaccatgacattgcaccatactccaacatggtattaggtgaagtcttaaatgaccgcggaaactggtca ggatatcttcctcacagacatccgcagccggaaacttattacttcctgtttgaccatccggaaggatttggggcaagctttgtggg agaccaggtatttaagagtacagacggaagcttctcagcgattccagggggagaacttcatcctcaggcagtggctccgggat accaaatgtatacttgctggatgatccgtcatctggaagggaacccatggcttcagacagacagaaatgaagacgaacgcta cgtttggcttcatgacgcagaattctaa Amino acid sequence (SEQ ID NO: 10) MGKVFGYPEFDVNGEKVLTTYDNDYKEMLMDIRVFRLKAGDVKTFCKEKEETAVLLLKGD VVFSFDETSKEVTRKDVFTEGPWAVHICTGAKVIVEAKADSEILVQSTMNDQTFESKLYAP EDAPWGYSCVGKFGNVAKRRVNTIFDHDIAPYSNMVLGEVLNDRGNWSGYLPHRHPQP ETYYFLFDHPEGFGASFVGDQVFKSTDGSFSAIPGGELHPQAVAPGYQMYTCWMIRHLE GNPWLQTDRNEDERYVWLHDAEF 5-keto-2-deoxygluconokinase - AR1Y2_1104 Nucleotide sequence (SEQ ID NO: 11) atgaagtatgttgaatttgaccagacaagaccaatggatttagtactcatcggaagggtagccatcgattttaacccggtagatta tttccacccgttatctgagtgcactaccttcaagaagtatgtgggaggatctccggcaaacatcgcagtgggcatcacaaggca cggaaagaaagccggattcatcggcaaagtttctgatgaccagttcggagagtatgtagtagacttcttcaataaagagggaat cgatacatcccatattacaaaatgtacgaacggagaaaagcttggacttacctttacagaaattctttccagagaagaaagca gcatcttaatgtaccgcaactgcatcgcagacttacagttatctgtggatgacattgacgaagaatacataaagaacacaaaa gcaatcctggtttccggaacagcattggcacagagcccatccagggaagcagtgttaaaagcagtgatgcttgccaagaaaa atgatacaaagatcatctttgacattgactatagagaatacaactggaaaaattccgatgagatttcaatctactattctttagtagc cagagaagcagatatcatcatgggatctagagaagaatttgacctgacagaaaaactgataaaaccgggcagaacagaca aagaatctgcacaggcatggaacactgaaaatgcaaagatcgttgtcatcaaacatggcaaaaaaggatctacagcatata ccaatgacggaaatgactattcaatcaaaccgttcccggttgaggcgttaaaaggctttgggggcggagacggatatgcatcc ggcttcttatatggaatatttgaaggatgggatatgatcgagtgtctggaattcggaagtgcggaagcggccatgatggtgagaa gccattcttgttctgaagaacttccaaaccctcaggaagtcaaagactttatccgcgagacaaaagacaaatatggcgaaatg attgcgagagtatag Amino acid sequence (SEQ ID NO: 12) MKYVEFDQTRPMDLVLIGRVAIDFNPVDYFHPLSECTTFKKYVGGSPANIAVGITRHGKKA GFIGKVSDDQFGEYVVDFFNKEGIDTSHITKCTNGEKLGLTFTEILSREESSILMYRNCIADL QLSVDDIDEEYIKNTKAILVSGTALAQSPSREAVLKAVMLAKKNDTKIIFDIDYREYNWKNSD EISIYYSLVAREADIIMGSREEFDLTEKLIKPGRTDKESAQAWNTENAKIVVIKHGKKGSTAY TNDGNDYSIKPFPVEALKGFGGGDGYASGFLYGIFEGWDMIECLEFGSAEAAMMVRSHS CSEELPNPQEVKDFIRETKDKYGEMIARV 5-keto-2-deoxy-D-gluconate-6 phosphate aldolase - AR1Y2_1054 Nucleotide sequence (SEQ ID NO: 13) atggcattagtcaaaatgaaacagttattagagcaggcaaaaaaggaaaacagaggatgcggtgcattcagtgtgggcaat atggaaatggtcaaaggggcgattcaggcagcggaggagatgaatacaccgatcatcctgcagatcgctgaagtgcggctc gcccattcaccgcttcatcttatggggccgatgatggtgcaggcggcaaaagaggcaaaggtggatgtggcagttcatctgga ccacggacttaacattgagactgtaaaaaaagcgctggaactgggatttacctctgttatgctggatgcatccagagattcgtttg aagaaaatatcagaaaaacaaaagaagttgtcgctctggcagcacagtacggagcaaccgtggaagcggaattagggctg gtaggcggaagcgaagacggaaagagtgaccatggaatccagtgcaccaagcctcaggacgccaaggtcttctgtgagca gaccggagtggatgccctggccgttgccattggaaatgcccacggggactatccggtagctccgactttggaatttggtgtattg gaagacattcacaatattactgccaaaccattggtgcttcacggcggaagcggtattacagatgaggatttcagaaaagccatc tctcttggaatctgcaaagtgaacattgcaactgcaagctttaacagcctgacaaaagaagtggaaaactatctggagacaga aggaaaacataattacttcgatatgaacgaagctatggtaaagggtgtctatgacaacgtaaaacgccatatccagatctttaa ctgcagataa Amino acid sequence (SEQ ID NO: 14) MALVKMKQLLEQAKKENRGCGAFSVGNMEMVKGAIQAAEEMNTPIILQIAEVRLAHSPLHL MGPMMVQAAKEAKVDVAVHLDHGLNIETVKKALELGFTSVMLDASRDSFEENIRKTKEVV ALAAQYGATVEAELGLVGGSEDGKSDHGIQCTKPQDAKVFCEQTGVDALAVAIGNAHGD YPVAPTLEFGVLEDIHNITAKPLVLHGGSGITDEDFRKAISLGICKVNIATASFNSLTKEVENY LETEGKHNYFDMNEAMVKGVYDNVKRHIQIFNCR Glyceraldehyde-3-phosphate keto-isomerase - AR1Y2_1336 Nucleotide sequence (SEQ ID NO: 15) atgcgtaaaacaatcgtagcaggaaactggaaaatgaacaaaacacctagcgagacagtagctttagttaatgaattaaagc cattggtagcaagcgaggtttcagatgttgtcttctgtgtgccggccatctgtattccggcagcactggaagctgcaaaaggaagt aacatcaacatcggcgctgagaacatgtattttgaagagagcggcgcttacacaggcgagatcgctccgaatatgttaacaga cttaggtgtgaaatatgttatcatcggacattctgagagaagagaatattttgcagaaacagatgagacagtgaataaaaaagt cttaaaagcttttgaacatggaattactccaatcgtttgctgcggtgagacacttgctcagagagagcagggtgtgaccatcgatt tcgtacgccagcagatcaagatcgcattccagggtgtgactgctgaccaggcaaagacagctgtcattgcatacgaaccgatc tgggctatcggaacaggaaaagttgcgacgacagaacaggctcaggaagtatgtaaagcgatccgtgagtgcatcgctgaa gtatacgatcaggcaacagcggacgctattcgtatccagtacggcggttctgtatccgctgcaagtgcaccagaattatttgcac aggaagacatcgatggaggattagtcggtggagctgctttaaaaccagactttggtaagatcgtgaattacaaataa Amino acid sequence (SEQ ID NO: 16) MRKTIVAGNWKMNKTPSETVALVNELKPLVASEVSDVVFCVPAICIPAALEAAKGSNINIGA ENMYFEESGAYTGEIAPNMLTDLGVKYVIIGHSERREYFAETDETVNKKVLKAFEHGITPIV CCGETLAQREQGVTIDFVRQQIKIAFQGVTADQAKTAVIAYEPIWAIGTGKVATTEQAQEV CKAIRECIAEVYDQATADAIRIQYGGSVSAASAPELFAQEDIDGGLVGGAALKPDFGKIVNYK Glyceraldehyde-3-phosphate dehydrogenase - AR1Y2_1334 Nucleotide sequence (SEQ ID NO: 17) atggcagtaaaagtagcgattaatggatttggacgtattggacgtcttgcattcagacagatgttcggagcagaaggttatgaag ttgtagcaatcaacgatttaacaaatcctaagatgttagcacatttattaaagtatgattctgcacagggaagatatgcattaggcg acaaggtagaagcaaaagaatcttccatcgtagttgacggaaaagaaatcgaaatctacgcagaagcagacgcaacaaa acttccttggggagaattagatgttgatgttgtattagaatgtacaggattctacacatctaaagacaaagcatccgcacacgttc aggcaggagctaagaaagttgttatttctgcgccagctggaaatgatcttccaactatcgtatataatgtaaaccacgatacattg acaaaagaagacacagtcatctcagcagcatcttgtacaacaaactgcttagcacctatggctgatgcactgaacaagtatgc accaatccagtctggtatcatgttaacagtacatgcttacacaggagatcagatgactcttgacggacctcagagaaaaggtga cttaagaagagcacgtgcagctgcagtcaacatcgtacctaactctacaggtgctgcaaaagctatcggattagttatcccaga attaaacggaaaattaatcggatctgctcagcgtgtaccggttcctacaggatcaacaacacttttaacagcagttgttaaaggt gacaatgtaactgttgaaggaatcaacgcagctatgaaagcagcagcaacagagtctttcggatacacagaagaagaatta gtatcttctgacatcatcggaatcaaatatggttctttattcgacgcaactcagacaatggttactgaagttggtgacggattatatg aagtacaggttgtttcttggtatgacaacgaaaactcatacacaagccagatggttagaacaatcaaatactttgcagaattagc ataa Amino acid sequence (SEQ ID NO: 18) MAVKVAINGFGRIGRLAFRQMFGAEGYEVVAINDLTNPKMLAHLLKYDSAQGRYALGDKV EAKESSIVVDGKEIEIYAEADATKLPWGELDVDVVLECTGFYTSKDKASAHVQAGAKKVVIS APAGNDLPTIVYNVNHDTLTKEDTVISAASCTTNCLAPMADALNKYAPIQSGIMLTVHAYTG DQMTLDGPQRKGDLRRARAAAVNIVPNSTGAAKAIGLVIPELNGKLIGSAQRVPVPTGSTT LLTAVVKGDNVTVEGINAAMKAAATESFGYTEEELVSSDIIGIKYGSLFDATQTMVTEVGDG LYEVQVVSVVYDNENSYTSQMVRTIKYFAELA Phosphoglycerate kinase - AR1Y2_1335 Nucleotide sequence (SEQ ID NO: 19) atgttaaacaagaaatcagtagatgatatcaacgtaaaaggaaaaaaagtcttagtgcgctgtgacttcaacgttccgcttcag gatggaaagatcacagatgagaaccgtcttgtggcagcacttcctacactaaagaagttaattgctgacggcggaaagctgat cctctgctcacacttaggaaaaccaaaaggggaaccgaaaccggagttatctcttgcgccagtagcagaaagattaagcga gttattaggacaggaagtaaagtttgctgcagatgacaacgtggtaggaccgaatgcaaaagctgcggtagaaggaatgca ggacggggatgtcattttacttcagaatacacgctacagagcagaagagacaaagaatggagaagagttcagcaaagaact tgcaagtctctgcgatgtttttgttaatgatgcttttggtaccgctcatagagctcactgctctaacgtgggagttacaaagttcgtgg acactgcagttgtaggatatttaatgcagaaagagattgatttcttaggaaatgcggtcaacaatccggaacgtcctatggtcgct atcttgggaggagcaaaggtttcctctaagatctctgtgatcaataacctgctagacaaagtcgatactttgatcatcggcggag gtatggcatatactttcatgaaagcattgggagaagaagttggagattcccttctggaagctgactacttagactacgcaaaaga aatgatggacaaggcaaaagaaaaaggtgtgaacttactgattcctgttgacactgtagttgctgatgacttctcaaatgacgcc aacatcaaaactgttgagagaggcggaatcgaagcaggatggcagggacttgacatcggaccaaagacaagagaactgtt ttcaaatgcactgaaagatgccaagactgtagtatggaacggaccgatgggatgctttgagatgccgaactttgcagcaggaa ccgttgcagttgcagaagcactggcagagatcgacgctacaactatcattggcggaggagattccgcagcggcagttaacca gctcggattcggagataagatgactcatatctctacaggtggtggagcatcactggaattcctggaaggaaaagaattaccag gcgttgcagcggcaaacgataaataa Amino acid sequence (SEQ ID NO: 20) MLNKKSVDDINVKGKKVLVRCDFNVPLQDGKITDENRLVAALPTLKKLIADGGKLILCSHLG KPKGEPKPELSLAPVAERLSELLGQEVKFAADDNVVGPNAKAAVEGMQDGDVILLQNTRY RAEETKNGEEFSKELASLCDVFVNDAFGTAHRAHCSNVGVTKFVDTAVVGYLMQKEIDFL GNAVNNPERPMVAILGGAKVSSKISVINNLLDKVDTLIIGGGMAYTFMKALGEEVGDSLLEA DYLDYAKEMMDKAKEKGVNLLIPVDTVVADDFSNDANIKTVERGGIEAGWQGLDIGPKTR ELFSNALKDAKTVVWNGPMGCFEMPNFAAGTVAVAEALAEIDATTIIGGGDSAAAVNQLG FGDKMTHISTGGGASLEFLEGKELPGVAAANDK Phosphoglycerate mutase - AR1Y2_0899 Nucleotide sequence (SEQ ID NO: 21) ttgaagttatatatgatgaggcacggagaaactccatggaataaagtgcggaggattcaggggcagtcagacgtggatctga gtgaagcgggcagggaagcagccaggctcaccaggagagcactgaaagatttccattttgatgcggcctacacgagcccg ctgagcagagcgagagaaacaggggagatcatcctggagggcagagggatccctctgctggaggatgaacggcttaagg aggccaacttcggaccttatgaaggggcacacatcaatgaattatatgaaagagaagaaccgattctggatttctttgaccggc cggaacagatggcctatattgaaggagcggagactccggctcaggtagtagaaagatccaggatatttttagaggaatttatac ttccgatggaaaaagaagcagaaagtgtgatcttatttacccacggagctttcatccacgggatgctgactaatatgtatcaaag agagatcagggacttttggaaaggaccgaagcttaagaattgttctatcagtacggctgaagtcagggacggtcagttccgcat tttgagtgaggctgaggtcttttactga Amino acid sequence (SEQ ID NO: 22) MKLYMMRHGETPWNKVRRIQGQSDVDLSEAGREAARLTRRALKDFHFDAAYTSPLSRAR ETGEIILEGRGIPLLEDERLKEANFGPYEGAHINELYEREEPILDFFDRPEQMAYIEGAETPA QVVERSRIFLEEFILPMEKEAESVILFTHGAFIHGMLTNMYQREIRDFWKGPKLKNCSISTA EVRDGQFRILSEAEVFY Enolase - AR1Y2_0982 Nucleotide sequence (SEQ ID NO: 23) atggattatttagagattgaaaaggtcataggaagggaaattattgattccaggggaaatcctacagtggaagcagaagttctttt agccggcgggacaatcggacggggcacagcacccagcggagcttcaactggagaatttgaggcgttggaattaagagacg gagataaggagcgttttggaggaaaaggtgtgtccaaggcagttcataatattaatacgatcattaacgatactttaaaagggat ggatgcatccgatacttacgcggtggacagagcgatgatcagcgtagacggaacaaaggataaatcaaagcttggggcca atgcgatccttgcggtttcgattgcatgcgcaaaggcggcatcggcaggcctggatctgccattataccgttttctgggcggtgtta atgccaaccgtcttccggtgccgatgatgaacattttaaacggaggtgcccatgcggccaacaccgtcgatgtacaggagttta tgatcatgcctgtgggagcagaaaatttcagggaagcactccggtggtgtacggaagtattccacgccttggcagctttgctgaa atccaaagggctggcaacctccgtgggtgatgaaggcgggtttgcgcctgaccttgcaagtgatgaggaagccatcgaatata ttttggaagctgttcaggcagcgggatatgagccgggcagtgattttgttctggctatggatgctgcttccagcgagtggaaaggc gcgaacaaaggtgaatatattcttcctaagagtggcaagaaatttacctcagaagaactggtggaccactggaaatcactttgt gagaaatatccgatcagctccattgaggatggattggatgaggaagactgggacggctggaaatacatgacccaggagcttg gagagaaaatccagctggtgggagatgacttatttgtaacgaatacggaacgccttggaaaaggtatcaagatgggatgcgg aaattctatcttgatcaagctgaaccagatcggttctgtgtcggagacattggaagctattaagatggcccataaagcgggttac acagcggtcacatcccaccgttcaggggagacagaagacacgaccatcgcagatctcgctgttgcacttaataccggacag atcaaaaccggtgcaccgagcagaagtgagagggtggcaaaatataatcagcttctgaggattgaagaggaactggggga aagtgccgtatacccgggagtcggaacattttag Amino acid sequence (SEQ ID NO: 24) MDYLEIEKVIGREIIDSRGNPTVEAEVLLAGGTIGRGTAPSGASTGEFEALELRDGDKERFG GKGVSKAVHNINTIINDTLKGMDASDTYAVDRAMISVDGTKDKSKLGANAILAVSIACAKAA SAGLDLPLYRFLGGVNANRLPVPMMNILNGGAHAANTVDVQEFMIMPVGAENFREALRW CTEVFHALAALLKSKGLATSVGDEGGFAPDLASDEEAIEYILEAVQAAGYEPGSDFVLAMD AASSEWKGANKGEYILPKSGKKFTSEELVDHWKSLCEKYPISSIEDGLDEEDWDGWKYM TQELGEKIQLVGDDLFVTNTERLGKGIKMGCGNSILIKLNQIGSVSETLEAIKMAHKAGYTA VTSHRSGETEDTTIADLAVALNTGQIKTGAPSRSERVAKYNQLLRIEEELGESAVYPGVGTF Pyruvate-flavodoxin oxidoreductase - AR1Y2_3042 Nucleotide sequence (SEQ ID NO: 25) atggcaagaaaaatgaaaaccatggatggtaacacagctgcagcacacgtgtcttacgcttttactgagacagctgctatctac ccaattacaccatcctcaccaatggcagaatcaacagaccagtgggcaacacagggaaagaaaaatattttcggacatcct gtaaaattagttgaaatgcagtcagagggcggagcagcaggaactgttcacggatctcttgcagcaggcgcattgacaacta catacactgcatctcagggattattactgatgattcctaatatgtacaagatcgcaggtgaattaatgccttgtgtatttgatgtatctg cacgtgcaatcgcatctcatgcactgaatatctttggtgatcactctgacgtttacgcttgtcgccagacaggttttgcaatgctttgc agctccagcgttcaggaagttatggacttaggcgctgttgctcatttatctacaatcaagggaagcgttccagttctccatttcttcg atggattcagaacatctcatgagatccagaagattgaaatgtgggacaacgaagatcttgcagatatggtagattacgatgctct tgaaaagttcagagcaaatgctttgaatccagaacatccggttctccgcggatctgctcagaatccagatatcttcttccaggca agagaagcatgcaacaaatactacgatgcattcccggcaatcgtcgaagattacatgaaccaggttaatgcaaagatcggta cagattataaattattcaactactacggagctgctgatgctgaatctgttatcattgcaatgggatctgtatgtgagactatcgatga gaccatcgattacttaacagcaaaaggcgaaaaagtcggtgttgttaaagtaagactttacagaccattcgtagctgaaaaatt actcgaagttatcccagagactgttaaaacaatcaacgttttagacagaacaaaagaaccgggatctcttggagagccattat acttagacgttgtttctgcattaagaggaacaaaattcgagcaggtaacaatcaacggaggacgttacggattaggatccaaa gatacaactcctgctgatatcatctctgtattcaataacaaagataagaaagaattcacagttgcgatcaacgatgatgtgacaa acttatctcttgaaagaggagaagctgtttcttctacaccagaaagcacagtaagctgtaagttctggggtcttggagcagatggt accgttggtgctaacaagaactccatcaagatcatcggtgaccacactgacaaatatgctcaggcatactttgattatgattcca agaaatccggtggtgttacaatttcccacttacgtttcggcgatgacccgatcaaagcaacttacctgatcaacaaagctgatttt gttgcatgtcactgtgctccgtacatgacaaaatacaacatggttcaggacttaaaagatggcggaacattcttgttaaactgtag ctggccggtagaagaaatcggagatcatcttccaggacaggtaaaagcttacatggcaaaacacaacatcaagttctatgtg atcgatggtatcaagatcggtaaagagattggacttggcggacgtatcaatactgtacttcagtctgcattcttcaaattatctgga attattccggaagcagacgcgatccagtatatgaaagacgctgctactgcttcttacagcaagaagggtgatcacatcgttaag atgaatcatgacgcgatcgaagctggtgctaagagtgttgtagaagttccggttcctgctgaatgggctgactgcggagaagaa agcttattacatccagtatccggagatagaaaagatcttgttgattatgttaacaacattcagaacgctgtcaatggacagattggt aacagccttaaggtaagcgacttagttccttacgctgacggtcatatgcctcagggatctgctgcatacgaaaaacgtggagttg ctgtagacgttcctacatggaatccggacaactgtatccagtgtaacttctgtgcatatgtatgtcctcatgcagttatccgtcctgtt gccatgacagaagcagaacttgctgcagcaccggaagctacaaaatctcttccgatgacgggaatgccagattacaaatttgt aatgacaactactgttcttgactgtacaggatgtggttcttgtgcaaatgtctgcccaggtaagaaaggcgagaaagctcttaca atggcaccactcgacagcatgagagatcagcaggaagtttacaactatggacagtctttacctataaaagaagatatctttgac aagtttaaaccagaatctgttaagggaagccagttcaagaaacctctccttgagttctcaggagcttgtgcaggatgtggagag actccatatgcgaaactgatcactcagttattcggagacagaatgtacattgccaatgcgacaggatgttcttctatctggggtggt tcttcacctgcaacaccttacacagtaaacagcgaaggacagggaccggcttggtctaactcactgttcgaagacaatgctga gtttggtttaggtatgttcacaggacagaatactttaagagagcagacaaaagaaaaggttgcagcattagcagaatctacag ataatgcagatgtaaaagcagcagcggctgaatacttagatacttacacagacggtaagaaaaacggagcagctactaaga aattagttgcagcactggaagcttgcggatgtgaagaaggaaaagaaatccttaagatgaaagattacttatctaagaaatctc agtggatcttcggtggtgacggatgggcttacgacatcggctttggcggtgttgaccatgtacttgcaagtggtgaagatgttaata tctttgtattcgatacagaggtttactctaacaccggcggacaggcatccaaatctacaccggcaggtgcgatcgctcagttcgc agcagcaggtaaggctgtgaagaaaaaagaccttgcagcaatcgcaatgagctacggatatgtatatgttgctcagatctctat gggtgctgattacaatcagacagtcaaagcgatcgcagaggcagaagcttatccaggaccatcactgatcatcggttatgctc catgtatcaaccacggtatcaagggtggaatgagcattgctcagtctgaagaaaagaaagcagttacatcaggatactggaa cttattccgtttcaaccctgaattagctgaagaaggaaagaatccattctcattagattctaaagagcctacaacagagtacaatg acttcatcatgggtgaggttcgttacaacgctcttgctcgccagaatcctgagagagctaaggagctgtttgagcaggcagaaa agaatgccaaagaaaaatatgctcgtttgaaagaattagcagataaataa Amino acid sequence (SEQ ID NO: 26) MARKMKTMDGNTAAAHVSYAFTETAAIYPITPSSPMAESTDQWATQGKKNIFGHPVKLVE MQSEGGAAGTVHGSLAAGALTTTYTASQGLLLMIPNMYKIAGELMPCVFDVSARAIASHAL NIFGDHSDVYACRQTGFAMLCSSSVQEVMDLGAVAHLSTIKGSVPVLHFFDGFRTSHEIQ KIEMWDNEDLADMVDYDALEKFRANALNPEHPVLRGSAQNPDIFFQAREACNKYYDAFPA IVEDYMNQVNAKIGTDYKLFNYYGAADAESVIIAMGSVCETIDETIDYLTAKGEKVGVVKVR LYRPFVAEKLLEVIPETVKTINVLDRTKEPGSLGEPLYLDVVSALRGTKFEQVTINGGRYGL GSKDTTPADIISVFNNKDKKEFTVAINDDVTNLSLERGEAVSSTPESTVSCKFWGLGADGT VGANKNSIKIIGDHTDKYAQAYFDYDSKKSGGVTISHLRFGDDPIKATYLINKADFVACHCA PYMTKYNMVQDLKDGGTFLLNCSWPVEEIGDHLPGQVKAYMAKHNIKFYVIDGIKIGKEIG LGGRINTVLQSAFFKLSGIIPEADAIQYMKDAATASYSKKGDHIVKMNHDAIEAGAKSVVEV PVPAEWADCGEESLLHPVSGDRKDLVDYVNNIQNAVNGQIGNSLKVSDLVPYADGHMPQ GSAAYEKRGVAVDVPTWNPDNCIQCNFCAYVCPHAVIRPVAMTEAELAAAPEATKSLPMT GMPDYKFVMTTTVLDCTGCGSCANVCPGKKGEKALTMAPLDSMRDQQEVYNYGQSLPIK EDIFDKFKPESVKGSQFKKPLLEFSGACAGCGETPYAKLITQLFGDRMYIANATGCSSIWG GSSPATPYTVNSEGQGPAWSNSLFEDNAEFGLGMFTGQNTLREQTKEKVAALAESTDNA DVKAAAAEYLDTYTDGKKNGAATKKLVAALEACGCEEGKEILKMKDYLSKKSQWIFGGDG WAYDIGFGGVDHVLASGEDVNIFVFDTEVYSNTGGQASKSTPAGAIAQFAAAGKAVKKKD LAAIAMSYGYVYVAQISMGADYNQTVKAIAEAEAYPGPSLIIGYAPCINHGIKGGMSIAQSE EKKAVTSGYWNLFRFNPELAEEGKNPFSLDSKEPTTEYNDFIMGEVRYNALARQNPERAK ELFEQAEKNAKEKYARLKELADK 3-oxoacid CoA transferase - AR1Y2_1115 Nucleotide sequence (SEQ ID NO: 27) atgggaaaagttaaaattatcacagcagatcaggctgctgccctggtggaggatcatacaacgatcacaaccagcggatttgt tgccagcggaatgccggaagctctcacaaaagctttggaaaaaagattcaaagaaaccggatcccccaaaaacctgacttt gttttatgctgccgcccagggaaaccgtgacggaagcggcgcggatcattttgcccatgaaggtatgacaaaacgtgtcatag gcggacattggaacatggttcctgcactgggacagatggttctggacaataaaatcgaaggctataatctgcctcagggaaca ctggcacagttataccgtgccatcgcaggtcacaaacccggcgttatcagtcatgtaggattaaatacatttgctgacccacgca ttgagggcggtaaattaaatgacattacaaccgaagatatcgtcgatgtagttgaaatcctgggagaagagaaattattgtaca aatcgttcccgatcaacatcggatttatccgcggtacatatgcagatgaacacggcaacgtaactctgtctcacgaatgtgccac cacagaggtcacaaccatggctcaggccgtaaagaacagcggcggaaaggtcgttgtacaggtagaaaaggtcgtttcag acggcaccttagatccaaaattagtcaagatccctggaatttatgtggatgccgttgtggaagtagaagacatgaaggatcacg aacaatgcgtgggctgtgattatgatggttccatgaccggagacttccgggttccgttaagcagtcttgagtacccgcctctttccg ccaagaagatcattggacgcagagcagccatggaactgacagaaaacacggttgtaaatctaggcattggtattccagagta catctccatggtagccaacgaagaaggcattggagattacatgactctgactgtagaggccggaccaatcggcggtgtacctc agggaggagctaaattcggaggcgctgtcaatgctgaatgtatcctagatcagccgtaccagtttgatttctatgacggcggcg gagttgactatgcattcttaggactcgcacaggcagataaagacggtaatatcaacgtaagcaagttcggtccaaggattgcg ggctgcggcggtttcgtcaatatcacccagaacgcaaaacgctgctacttctgcggaacttttactgcaggaggtctgaagaca tccgtaaaagacgggaaacttatcattgaccaggaaggaaaatcaaacaaattcctggataccgtagaacagatcaccttca gcggtgaatacgcaaataaagtcggccagccggttctctatatcacagaacgtgctgtattcgaactcagaaaggacggcgtc tatctgacagaggttgcccctggtatcgatatccagacacagatcatcgatcatatgggatttgctccaaagatggaaggaacg ccaaagttcatggatgaaagaatcttcaaagatgagctgatgggcctgaagcacgattaa Amino acid sequence (SEQ ID NO: 28) MGKVKIITADQAAALVEDHTTITTSGFVASGMPEALTKALEKRFKETGSPKNLTLFYAAAQG NRDGSGADHFAHEGMTKRVIGGHWNMVPALGQMVLDNKIEGYNLPQGTLAQLYRAIAGH KPGVISHVGLNTFADPRIEGGKLNDITTEDIVDVVEILGEEKLLYKSFPINIGFIRGTYADEHG NVTLSHECATTEVTTMAQAVKNSGGKVVVQVEKVVSDGTLDPKLVKIPGIYVDAVVEVED MKDHEQCVGCDYDGSMTGDFRVPLSSLEYPPLSAKKIIGRRAAMELTENTVVNLGIGIPEY ISMVANEEGIGDYMTLTVEAGPIGGVPQGGAKFGGAVNAECILDQPYQFDFYDGGGVDYA FLGLAQADKDGNINVSKFGPRIAGCGGFVNITQNAKRCYFCGTFTAGGLKTSVKDGKLIID QEGKSNKFLDTVEQITFSGEYANKVGQPVLYITERAVFELRKDGVYLTEVAPGIDIQTQIIDH MGFAPKMEGTPKFMDERIFKDELMGLKHD Acyl-CoA dehydrogenase - AR1Y2_1117 Nucleotide sequence (SEQ ID NO: 29) atgaattttgaattaacagagcagcaggcagccattcaggaaacagcaaggaactttgctcagacagaactgcagccaggt gtgctggagagagatgcaaacagtgagtttccggtagatctttataagaagatgggggatatgggcctgatcggtcttccatatc cgaaagaagtcggaggacagggagccgattatctttcttatgcactggcagtggaagagatctcaaaagtagatgcctctgtg ggtatttcctattctgtttccacctctctgtatggcggaagcattatgaactctgatgcttccgttgagaaaaagaatgaatttctagca ccggtactgtccggacagcatttcggatcctttggactcacagagcccaatgccggatcagacgcaggcggatgtgtcactgtg gctgaaaaagatggggacgaatacatattaaatggtatgaagtgttttaacaccaacggacctttggccgattatacagcggtat atgccctgacagaacctgagaagaaagcaaagggtctttcctgctttgtagtaaaaaaaggaactcctggattttctgtaggca aggtggaggataagatgggaatccgctctgcgcaggtctctgagatgatcctggaaaatgtcagagtacctgcagagaatatg gtcgttccatctggggacggatttaagctggccatgaagactttggatggaggacgcatcggcgttgccgcgcaggggcttggt atcgcggagggcgcatttgagatcgcaaaagaatacttaaagagcagagaacagttcggcaaaccattatataaaaaccag tatcttgcatttaagatggcggaacttgaaatggagatcgacgctgcaagatacatgctttacaaagcggctacagataaacac gagggaagatcttactcaatcccggcagcaaaggcaaaatacctttgtacagaggccgctatgcatgtgacaacagaagca gtacagatgttaggtggaaatgggtatatgaagggttaccatgtagaacgtatgatgagagatgcgaagatcactcagatctat gagggaaccaatgaaatccagaagctcgttgtaagcggagctatcttcagatag Amino acid sequence (SEQ ID NO: 30) MNFELTEQQAAIQETARNFAQTELQPGVLERDANSEFPVDLYKKMGDMGLIGLPYPKEVG GQGADYLSYALAVEEISKVDASVGISYSVSTSLYGGSIMNSDASVEKKNEFLAPVLSGQHF GSFGLTEPNAGSDAGGCVTVAEKDGDEYILNGMKCFNTNGPLADYTAVYALTEPEKKAK GLSCFVVKKGTPGFSVGKVEDKMGIRSAQVSEMILENVRVPAENMVVPSGDGFKLAMKTL DGGRIGVAAQGLGIAEGAFEIAKEYLKSREQFGKPLYKNQYLAFKMAELEMEIDAARYMLY KAATDKHEGRSYSIPAAKAKYLCTEAAMHVTTEAVQMLGGNGYMKGYHVERMMRDAKIT QIYEGTNEIQKLVVSGAIFR Enoyl-CoA hydratase - AR1Y2_1116 Nucleotide sequence (SEQ ID NO: 31) atgaacaatttattaatggaagtagaaaacgaagtcgcagttgtaacaatcaacagaccaaaatcattaaacgctttaaacagt gaaactttagctgagttagaccagtgctttacagagatttcaggacgcaaggacatcagagtggtgatcctcacaggatcagg cgaaaaatcctttgtagctggtgctgatatctctgaaatggtcaatgcaactcctgcagaaggaagacagatgggtcttttggca aaagaagcatttcttaagttagagacaatgcctcaggtaaccatcgctgccgtcaacggttacgctctgggaggcggatgcga gatctccatggcatgtgatatccgtgtagctgcggaaaacgcaaaattcgcacagccagaaacaggacttggaattcttccgg gattcggcggaacacagcgtctctcccgtttagtaggaaaaggacgcgcaaaggaattgatctttacatgtgaccagatcgatg ccgaagaagcttacagaattggtcttgcaaacaaagtagtgcctcaggcggagctgatcgattactgtaagaagatggctgca aagatcatgtccaaaggaagctacgcaatttcccttgcaaaagaagcgatcaacacaggaatggacacagacttaagcagc ggtcttacattagaagctgacttattcggacttgcattctccactgctgacaaaaaagagggtatgacagcattccttgaaaaacg taaagctgatttaaaagatttctag Amino acid sequence (SEQ ID NO: 32) MNNLLMEVENEVAVVTINRPKSLNALNSETLAELDQCFTEISGRKDIRVVILTGSGEKSFVA GADISEMVNATPAEGRQMGLLAKEAFLKLETMPQVTIAAVNGYALGGGCEISMACDIRVAA ENAKFAQPETGLGILPGFGGTQRLSRLVGKGRAKELIFTCDQIDAEEAYRIGLANKVVPQA ELIDYCKKMAAKIMSKGSYAISLAKEAINTGMDTDLSSGLTLEADLFGLAFSTADKKEGMTA FLEKRKADLKDF Acryloyl-CoA dehydrogenase - AR1Y2_1050 Nucleotide sequence (SEQ ID NO: 33) atggttgaatttaaattgacaaaagaacagctgcttgcacagcagatgttcaaagatttcgcagagacagaaatcaagccaatt gctagggacatggatgaaacagaagaattcagcatggaactgcttgagaaaatgaaaaaattcggtcttatgggaattccata ttccaaagaatacggcggagaaggggcagacgttttaacttatacactctgtatggaagagatgtctaagttagatgcttccaca ggaatcacaatttccgtacatacatcattgtgctgttcctgcatcaatgattttgcttcagaagagcagaaacaaaaatttttacgtc cgttggttgacggttctaaagtgggatgctttggtcttacagagccgggagcaggtaccgatgccagcggtgtgaagacaaatg ccgtattggacggcgatgaatatatcttaaacggacagaaggtgttcactacaaactcaggctttgccgatacatttattatttttgc agttacagacaaaactgcaggtacaagaggtatgtctgcatttatcgtggacaggaatacaccgggattagaagtcagcaag aatatccctcgtatgggtatccgtgctgcgtcaaactgtgaagttgctttagttgatgtgagagtaccgaaggaaaacctgatcgc gggcgagggaaaaggatataagatcgctatgtcagcgctggcaggcggacggatcggaatcggcgctcagtccgtaggaa tcgcacagggtgctttaaacgaggccattgcatatgtaaaggaaagaaaacagttcggaaaaccgatttctaaattccagaat acacagttcctgatcgcagaactccaagtgaagatcgacgctgcgcgccttatggtatggagagcggcaaaatcaaaagac gatcatgaaaactatgctcctctggcagcagcgtgcaaactgtttgcatctgacgtggcagtggaagtgacaagagcagccgt acagcttcttggaggatatggatactccagagaatatccggtagagagaatgtaccgtgatgctaagatcacagagatttacga aggtacatctgaagctatgaagatgatcgtcggcggcggacttttaagataa Amino acid sequence (SEQ ID NO: 34) MVEFKLTKEQLLAQQMFKDFAETEIKPIARDMDETEEFSMELLEKMKKFGLMGIPYSKEYG GEGADVLTYTLCMEEMSKLDASTGITISVHTSLCCSCINDFASEEQKQKFLRPLVDGSKVG CFGLTEPGAGTDASGVKTNAVLDGDEYILNGQKVFTTNSGFADTFIIFAVTDKTAGTRGMS AFIVDRNTPGLEVSKNIPRMGIRAASNCEVALVDVRVPKENLIAGEGKGYKIAMSALAGGRI GIGAQSVGIAQGALNEAIAYVKERKQFGKPISKFQNTQFLIAELQVKIDAARLMVWRAAKSK DDHENYAPLAAACKLFASDVAVEVTRAAVQLLGGYGYSREYPVERMYRDAKITEIYEGTS EAMKMIVGGGLLR Acryloyl-CoA dehydrogenase/Etf - Electron transfer flavoprotein, beta subunit - AR1Y2_1051 Nucleotide sequence (SEQ ID NO: 35) atgaaaatcgttgtttgtgcaaaacaagtaccagatacaactgaagtaaaattagatccaaagaccaacactctgatcaggga tggtgttccgagtatcatcaacccagatgacaaagccggaatcgaagctgccctgcagttaaaggaaaaatgcccgggaag cactgtgactgttgtttccatgggaccgcctcaggcagatgtggcattgagagaagcacttgctatgggatgtgacgatgcagttc tggtttctgacagagcattcggaggagcagatacatgggcaacatcttccactatcgcggcagcgatcaaaaaattggattacg atgtcatcatcacaggacgccaggcgattgacggagataccgctcaggtaggccctcagatcgcagaacatcttggaattcct caggtgagctatgtcgaagccctgaatgtggaaggggaagacactttgatcgtccagaggcagtttgaagaccgccatcaga tcattgaagtaaagactccttgcctgatcactgctttggctgaattggcaacacctagatatatgacagtccacggtgcatttgacg catacagagaaaaagaagtcagcgtctggggacttgcagacttagaagacactgtagaccaggcaaatatcgggttaaaag gatctcctacaagagtaaagaaatcctttacaaaacaggccaaaggtgcaggaactattttaaaagatttatcagcagacgaa gctgttgcatccattgttgataaacttcaggaaaagcacatcatttaa Amino acid sequence (SEQ ID NO: 36) MKIVVCAKQVPDTTEVKLDPKTNTLIRDGVPSIINPDDKAGIEAALQLKEKCPGSTVTVVSM GPPQADVALREALAMGCDDAVLVSDRAFGGADTWATSSTIAAAIKKLDYDVIITGRQAIDG DTAQVGPQIAEHLGIPQVSYVEALNVEGEDTLIVQRQFEDRHQIIEVKTPCLITALAELATPR YMTVHGAFDAYREKEVSVWGLADLEDTVDQANIGLKGSPTRVKKSFTKQAKGAGTILKDL SADEAVASIVDKLQEKHII Acryloyl-CoA dehydrogenase/Etf - Electron transfer flavoprotein, alpha subunit - AR1Y2_1052 Nucleotide sequence (SEQ ID NO: 37) atgagcagagacgtatatgtattcgctgagcagagagacggcgaacttcagaaagtcggaatcgaattaattggtaaagcaa gagaattagcagatgatcttggacagcaggtcgttgccgtgctgcttggggcaggcgtaaaagaaaaagcccaggaattagtt gcctgcggtgcagataaagttgttgtcgtagatgacattatgctggcagattatgtgacagagccatacacaaaggcactgaca gctgtgattaacgcaaaagatcctgagatcgtgctttatggtgcatcttccatcggacgtgaccttgccccaagagtatctgcaag gatccatactggattgacagcggactgtactgcacttgccattgatgaagagacaaagctcctcatgatgacccgtccggcattt ggcggaaatatcatggcgaccatcgtgtgtgaagacttccgtcctcagatggcaacagtccgtccaggagtaatgaaagcctt ggaaaacgatgcatccagaagcggtgaagtggaagagttcaaagtagaattctctgatgcagacatgaatgtaaaagtccgt gaaactgtaaagacagcacataaatctgtagacattacagaggctaagatccttgtttccggtgggcgcggaatcggaagcg ctgacaagttcaaggtgttagaggaactggcggatgtcatggaaggtgaagtgtcttcttccagagcatgtgtagattccggatg gatcagtgctgaccgccaggtaggacagacaggaaagactgtgcgtccggaattatatctggcctgcggcatctcaggagcg atccagcatgcagccggtatggagaactcagagtttatcgtagccatcaaccgtgatgaggatgcgccgatctttgatattgcag acctcggcatcgttggagacttaaataccatcgtaccgaaacttacagaagctgtgaaggcggtaaaaggaaaataa Amino acid sequence (SEQ ID NO: 38) MSRDVYVFAEQRDGELQKVGIELIGKARELADDLGQQVVAVLLGAGVKEKAQELVACGAD KVVVVDDIMLADYVTEPYTKALTAVINAKDPEIVLYGASSIGRDLAPRVSARIHTGLTADCTA LAIDEETKLLMMTRPAFGGNIMATIVCEDFRPQMATVRPGVMKALENDASRSGEVEEFKV EFSDADMNVKVRETVKTAHKSVDITEAKILVSGGRGIGSADKFKVLEELADVMEGEVSSSR ACVDSGWISADRQVGQTGKTVRPELYLACGISGAIQHAAGMENSEFIVAINRDEDAPIFDIA DLGIVGDLNTIVPKLTEAVKAVKGK Inosose isomerase - AR1Y2_1058 Nucleotide sequence (SEQ ID NO: 39) atgaaaatcggatttaacgaagcaactgcactggaatgtaaaggacagtctctgatggctgacttagaagcgtgtgaaaaata cggatttgattacatcgagatcagatttgactgtgtaaaggattatttgaaagaacacacactggaagaactggcggactggttt aaaaaccatcatttaaaaccatgggcttataataccttgatcttttttaaccagagagacgaagccggagaaaaagagattgac gaagagactgattttatcattgaagtgtgcaaggccatcggcatgaagatgctgatcactgttccgtcctttgatgtaaaggataa gagcatcacagagatcaaagaggaagcagtagaacgtctccgttatttatccgataaggtgggagaagatattaagatatcac tggaattctgcggggcgccgaactgctccatcaaccagtttgggacagcttacgatgtagtgaaagcaacagaccgtgacaat gtaggggtaacagtggataccttccatttccatgagatgtgttctaagttagaagatttagaagcagcggacggaaagaagatc tttgcttaccatctgaatgactgtgaggatctgcctctgggatcatgcggtgatgataaacgcctgtggccgggagaaggtgtggt agatcatgcaggaatcgcagctgccttaaagaagatcggattcgacggggtatgtaccattgaagaattccgtccagaatatta tgaaatgtcccatgacgagaatgtgaaaaagtctgctgaagtgacaagggatttcgtagcaaaatactttgcataa Amino acid sequence (SEQ ID NO: 40) MKIGFNEATALECKGQSLMADLEACEKYGFDYIEIRFDCVKDYLKEHTLEELADWFKNHHL KPWAYNTLIFFNQRDEAGEKEIDEETDFIIEVCKAIGMKMLITVPSFDVKDKSITEIKEEAVER LRYLSDKVGEDIKISLEFCGAPNCSINQFGTAYDVVKATDRDNVGVTVDTFHFHEMCSKLE DLEAADGKKIFAYHLNDCEDLPLGSCGDDKRLWPGEGVVDHAGIAAALKKIGFDGVCTIEE FRPEYYEMSHDENVKKSAEVTRDFVAKYFA Lactate dehydrogenase - AR1Y2_2463 Nucleotide sequence (SEQ ID NO: 41) atgacatataaaatgagaaaaatagtgatcataggggccggacatgtgggaaccatgtgcggcctgagtcttatgtaccgcgg agaagtggacgaattggtattcatagacatcgataaggaaaaggcatacagccaggcgctggaccttagtgatgccgtctcct tcctgccccggcagatcacggtgcgcaccggggattatgaagatgtggaggacgctgacatcatcgttatggccgctggtgttt ccaggctgcccggtcagacaaggctggatatgctggacgattccatccgcatcatgaaagaagtcaccagccatttaaaaga taagaagattcagggcatcctcatcagtatctccaatcctgccgacattgtggcggattatctgagaaaacaactgggccttccg agaaaccgctgcttcagcaccggtacttccctggactcctgccgtctcagaaggattctttcccaaagaatgcacttagaccgg aattccattcaggcctttgtcatgggagaacacggagattcccaaatgatcccgttttctgcggtacatatagccgggaaaccatt gcttcagtggatgcaagatgaaccggaacggtacggaagtctcgatctttcacagattgaaacggagaccgccaacgccgg ccatgaagtgatcgaaggaaagggcagcacagagtttggtatcggcatcgccctgtccgagatcgtccagtccattttccacg attcaaaaaaggtccttcccgcttcgcctctgctggaaggagaatatggacagcatggcgttcacgccggtgtcccctgcgtgat tggaaaagccggaattgaaaagatcattgagatccctctcacagaccgggagcaagagaaatttgaccattcctgcgatgtg atcagaacgtttattcaagatctctga Amino acid sequence (SEQ ID NO: 42) MTYKMRKIVIIGAGHVGTMCGLSLMYRGEVDELVFIDIDKEKAYSQALDLSDAVSFLPRQIT VRTGDYEDVEDADIIVMAAGVSRLPGQTRLDMLDDSIRIMKEVTSHLKDKKIQGILISISNPA DIVADYLRKQLGLPRNRCFSTGTSLDSCRLRRILSQRMHLDRNSIQAFVMGEHGDSQMIP FSAVHIAGKPLLQWMQDEPERYGSLDLSQIETETANAGHEVIEGKGSTEFGIGIALSEIVQSI FHDSKKVLPASPLLEGEYGQHGVHAGVPCVIGKAGIEKIIEIPLTDREQEKFDHSCDVIRTFI QDL Acetaldehyde dehydrogenase - AR1Y2_1414 Nucleotide sequence (SEQ ID NO: 43) atgggaagatttacattacctagagatttgtactttggaaaaggatcacttgagacactgaagacgctggacggaaaaaaagc tgttttagtcatcggcggcggatctatgaaacgttttggatttgtagaccaggttgttgattatttaaaagaagcaggcatagagac aaaattaattgagggagtagagccggacccttctgttgagaccgtatttaaaggtgccgagattatgagagagtttgaaccgga ctggatcgtggcaatgggcggaggatctccgatcgatgctgcaaaagctatgtggatcttctatgaacatccggaaaccacattt gacgatgtaaaagacccattcacagttccaaaactcagaaacaaagcaagattccttgcaatcccttcaacttcaggaacagc tacggaagtgacggcatttgctgttatcacggactacagttcaggcattaaatatccgctggcagactttgagatcacaccggat gttgccattgtagaccctgcactggcagagacgatgcctccgaaactgacctcttatacaggaatggatgcactgacccatgcg attgaagcatatgttgccggactgcattcaccattttcagatcctttggcaatcgatgccatcgagatggtatttgacaacttaaaag cttcctatgagggagacatgaccgcacgtgaaaatatgcactatgcacaatgtcttgcaggaatgtcattctctaatgcactgtta ggaattgtacattctttagcgcataagacaggagcagtttttgatacaggacatatcacacacggatgtgcgaacgctatctatct tccgtatgtgatccagtttaatgcaaaggtatgcgaagaccgctatgcagccattgcaagaaagatcggcctccctggaaattc cgataaagcactgacactttctttgattgaagcaatccgggatatgaacaagaagctgaacattgtttccaacctgaaagatttc ggaatcaatgaagaagaattcaaccagaagaagaggatgatcgcggagcgtgctgtggcagacgcatgtacaggatctaat cctagagaaacctctgtagatgacatggaaaaagtgttagagtgcatctactacggaaaagacgtaatattctaa Amino acid sequence (SEQ ID NO: 44) MGRFTLPRDLYFGKGSLETLKTLDGKKAVLVIGGGSMKRFGFVDQVVDYLKEAGIETKLIE GVEPDPSVETVFKGAEIMREFEPDWIVAMGGGSPIDAAKAMWIFYEHPETTFDDVKDPFT VPKLRNKARFLAIPSTSGTATEVTAFAVITDYSSGIKYPLADFEITPDVAIVDPALAETMPPKL TSYTGMDALTHAIEAYVAGLHSPFSDPLAIDAEMVFDNLKASYEGDMTARENMHYAQCLA GMSFSNALLGIVHSLAHKTGAVFDTGHITHGCANAIYLPYVIQFNAKVCEDRYAAIARKIGLP GNSDKALTLSLIEAIRDMNKKLNIVSNLKDFGINEEEFNQKKRMIAERAVADACTGSNPRET SVDDMEKVLECIYYGKDVIF Alcohol dehydrogenase - AR1Y2_2121 Nucleotide sequence (SEQ ID NO: 45) atgaaaataagtccgaaagtccgtgaatttttgtgccttaccgcacatcctcagggctgcagaaaaaatgttgaagatcagatta catatgtaaaaaaacacagcggtgttgagaatgggccgaaaaaggtcctggtcatcggctcatccacgggatatggcctggc atcaaggatcaccgctgcattcgggtgcggagcggataccttgggtgtcatgtttgagagaccggcggccggtaaacgtaccg ccactgccggatggtataatacagctgcatttgaacaggcggcggccagagaaggcttatatgcgaagacggtcaacgcag atgcattttccagggaagtaaaagaccaggtcatccaactgatcaagaaggatttcggtaaggttgacgctgtcatttacagtct ggctgcaccgagaagaacgacagaggacggcacggtttatcagtctgtcttaaagacaacaggggaagattttacaaataa gaacctgaaccttaaagataataccatcagtgagaaaaccatcgaggctgccacagaggaagaagtgaaagctaccgtga aggtcatgggcggggaggactggaaggcatggatccaggcgcttaccgatgcggatgccattgaaaagggcgcagtcacct tcgcatattcttatatcggacctaagcttacatatcctatctattttgagggaaccatcggtgccgcgaagaagcatcttcataaga cggcgggtgagatcaatgaggaattctcaaaggatggaatcaaagcatacatctccgtcaataaggggctggtgacacagg ccagttctgccattccgatcgtaccgctttatatggctgtgctgtaccgcgttatgaaagaaaagggacttcatgaaggctgtatcg aacagatcgtaaggctgttttctgaaaaggctgtctttggacaggccaagacagatgaacagggtctgatccgtctggatgact gggaactgcgcccggaagtccaggaagaagtggaacgccgctgggagaaggtctgcaccgaaaatgtccaggagtattct gatattgacggatactgggatgatttctaccaaatgttcggcttccgtatggatggagtggactacgaggaggatcttgacccttct gtggatatcccaagcatttccggccaagaatag Amino acid sequence (SEQ ID NO: 46) MKISPKVREFLCLTAHPQGCRKNVEDQITYVKKHSGVENGPKKVLVIGSSTGYGLASRITA AFGCGADTLGVMFERPAAGKRTATAGWYNTAAFEQAAAREGLYAKTVNADAFSREVKD QVIQLIKKDFGKVDAVIYSLAAPRRTTEDGTVYQSVLKTTGEDFTNKNLNLKDNTISEKTIEA ATEEEVKATVKVMGGEDWKAWIQALTDADAIEKGAVTFAYSYIGPKLTYPIYFEGTIGAAKK HLHKTAGEINEEFSKDGIKAYISVNKGLVTQASSAIPIVPLYMAVLYRVMKEKGLHEGCIEQI VRLFSEKAVFGQAKTDEQGLIRLDDWELRPEVQEEVERRWEKVCTENVQEYSDIDGYWD DFYQMFGFRMDGVDYEEDLDPSVDIPSISGQE Pyruvate kinase - AR1Y2_2344 Nucleotide sequence (SEQ ID NO: 47) atgctgacaaaaaaaacaaagattgtttgcacgatggggcctgcgacagatgatgatgcggtgctcaaacagctgatgctgg aaggaatggatatcgcgaggctgaatttctctcacggtgaccatgaggaacagcttggaaggatcaagagaattaaaagattc cgtgaagaactgaatattccgatcgcgatcttactggatacaaaaggacctgagatccgtacaggacttctggagacagacgg agacgtggaattaaaagaaggaaatgaatttgttctgaccacaagggacatcaaaggaaatgattctatcgtagcaattacat acgaagagcttccgcaggatgtcacagaaggaaatacaatcctgatcgatgacggtctgatcgaactgagagtcaaagaga tcaaagacggaacagatattgtatgtgaaattgtaaacggcggacttttaggaagccgtaagggagtgaacgtaccgaacgt gcgcgtaaatcttccttccatcacagaaaaggataagagagacattgagttcggacttgaaaacggcattgattttatcgcggct tctttcatccgtaacgcagatgcagtcaatgagatcaaggacatcgtaaaagcccacaacatggaagtcggcgttatctccaa aattgaaaacgtggagggtgtggaaaatattgaatccatcatccaggcttctgacggaatcatggtagcccgtggagatttaggt gtggaaattcccgcagaggaagttccgtttatgcagaaagcaatcattaagaaatgcaacaatgcatttaagccagtcatcac agctacacagatgttagactctatgatcagaaacccacgtccgacaagagcggaagtaacagacgttgccaatgctatttatg acggaaccgatgcgattatgctttctggagaaaccgcgaaggggaaataccctgtggaggccgtaaggatgatgaaccaga tcgccatctccacagaactgcatctggatacgaagatcaaagattttcgttccatctatgtaagccgtggaatctcagcagcggtt gcttattctgctgtacagactgctcataatattaacgcaaaatgtatcctggcgtccagtatgtccggatttacggcaaggatcgtat ctaagttcaaaccggatgcacagatcattggcttgtctccggatgaagcggttgtgcgtaagatgcagctttactggggagtgcg tccgtttaagtcacataaggcttcctctaccagagaacttttggatgaagctacggatatcgtactgaatgcagatcttgcacagg agaacgacatcctggtactgaccggaggaggtccggcagaccaccgtggaaaaggcgtgacaaacatgctgaaagtagta aaaatcggcgaataa Amino acid sequence (SEQ ID NO: 48) MLTKKTKIVCTMGPATDDDAVLKQLMLEGMDIARLNFSHGDHEEQLGRIKRIKRFREELNIP IAILLDTKGPEIRTGLLETDGDVELKEGNEFVLTTRDIKGNDSIVAITYEELPQDVTEGNTILID DGLIELRVKEIKDGTDIVCEIVNGGLLGSRKGVNVPNVRVNLPSITEKDKRDIEFGLENGIDFI AASFIRNADAVNEIKDIVKAHNMEVGVISKIENVEGVENIESIIQASDGIMVARGDLGVEIPAE EVPFMQKAIIKKCNNAFKPVITATQMLDSMIRNPRPTRAEVTDVANAIYDGTDAIMLSGETA KGKYPVEAVRMMNQIAISTELHLDTKIKDFRSIYVSRGISAAVAYSAVQTAHNINAKCILASS MSGFTARIVSKFKPDAQIIGLSPDEAVVRKMQLYWGVRPFKSHKASSTRELLDEATDIVLN ADLAQENDILVLTGGGPADHRGKGVTNMLKVVKIGE

[0117] Should there be an inconsistency between the sequences disclosed in the description and the sequences disclosed in the sequence listing, the sequences disclosed in the description are preferred. Alternatively, the sequences of the sequence listing may be used.

[0118] Experimental Support

[0119] Bacterium Comprising Myo-Inositol to Propionate Pathway

[0120] The present inventors found that myo-inositol can serve as carbon and energy source for a bacterium according to the present disclosure, e.g. Anaerostipes rhamnosivorans as previously isolated from stool of a healthy infant (Bui et al 2014 International Journal of Systematic and Evolutionary Microbiology 64: 787-793).

[0121] FIG. 1 shows that this bacterium is able to ferment efficiently myo-inositol to propionate. The experiment was performed twice.

[0122] Proteomics

[0123] A complete inositol fermentation pathway has been identified in the closed genome of Anaerostipes rhamnosivorans, which can thus be introduced in any bacterium of choice.

[0124] Method for Proteomics

[0125] To identify the proteins involved in the pathway, the protein abundances in cultures growing with two different substrates were examined with liquid chromatography-mass spectrometry/mass spectrometry.

[0126] Anaerostipes rhamnosivorans was grown in 4 replicates in 100 ml bicarbonate-buffered medium containing 40 mM myo-inositol or containing 40 mM rhamnose as carbon and energy sources.

[0127] Cells were collected in the exponential phase by centrifugation at 4700 g at 4° C. for 20 min. Cell pellets were washed twice and suspended in 0.5 ml of 100 mM Tris-HCl (pH 8). Protein extraction and digestion were performed as described previously (Bui et al., 2015). After the digestion, the samples were kept at −20° C. upon the analysis. The samples were analysed by injecting 4 μl sample over 0.10*250 mm ReproSil-Pur 120 C18-AQ 1.9 μm beads analytical column (prepared in-house) with an acetonitrile gradient at a flow of 0.5 ul/min with a Thermo EASY nanoLC1000. The gradient consisted of an increase from 9 to 34% acetonitrile in water with 1 ml/l formic acid in 50 minutes followed by a fast increase in the percentage acetonitrile to 80% (with 20% water and 1 ml/l formic acid in both the acetonitrile and the water) in 3 minutes as a column cleaning step. An electrospray potential of 3.5 kV was applied directly to the eluent via a stainless steel needle fitted into the waste line of the micro cross. Full scan positive mode FTMS spectra were measured between m/z 380 and 1400 on a Q-Exactive HFX (Thermo electron, San Jose, Calif., USA) in the Orbitrap at high resolution (60000). MS and MSMS AGC targets were set to 3.10.sup.6, 50000 respectively or maximum ion injection times of 50 ms (MS) and 25 ms (MSMS) were used. HCD fragmented (Isolation width 1.2 m/z, 24% normalized collision energy) MSMS scans of the 25 most abundant 2-5+ charged peaks in the MS scan were recorded in data dependent mode (Threshold 1.2e5, 15 s exclusion duration for the selected m/z+/−10 ppm). LCMS runs with all MSMS spectra obtained were analysed with MaxQuant 1.6.3.4 (Cox et al., 2008) using the “Specific Trypsin/P” Digestion mode with maximally 2 missed cleavages and further default settings for the Andromeda search engine (First search 20 ppm peptide tolerance, main search 4.5 ppm tolerance, MSMS fragment match tolerance of 0.5 Da, Propionamide (C) set as a fixed modification, while variable modifications were set for Protein N-terminal Acetylation and M oxidation which were completed by non-default settings for de-amidation of N and Q, the maximum number of modifications per peptide was 5 (Cox et al., 2011). Anaerostipes rhamnosivorans database from NCO (CP040058) was used together with a contaminants database that contains sequences of common contaminants like Trypsins (P00760, bovin and P00761, porcin) and human keratins (Keratin K22E (P35908), Keratin K1C9 (P35527), Keratin K2C1 (P04264) and Keratin K1CI (P35527)). The “label-free quantification” as well as the “match between runs” options were enabled. De-amidated peptides were allowed to be used for protein quantification and all other quantification settings were kept default.

[0128] Filtering and further bioinformatic analysis of the MaxQuant/Andromeda workflow output and the analysis of the abundances of the identified proteins were performed with the Perseus 1.6.2.1 module (available at the MaxQuant suite). Accepted were peptides and proteins with a false discovery rate (FDR) of less than 1% and proteins with at least 2 identified peptides of which at least one should be unique and at least one should be unmodified. Reversed hits were deleted from the MaxQuant result table as well as all results showing a normalised label free quantitation intensity (LFQ) value of 0 for all inositol and rhamnose injections. The normal logarithm was taken from protein LFQ MS1 intensities as obtained from MaxQuant. Zero “Log LFQ” values were replaced by a value of 5.9 (A value slightly lower than the lowest measured value) to make sensible ratio calculations possible. Relative protein quantitation of inositol to rhamnose was done with Perseus by applying a two sample Ttest using the “LFQ intensity” columns obtained with FDR set to 0.05 and S0 set to 1. nLC-MSMS system quality was checked with PTXQC (Bielow et al., 2016) using the MaxQuant result files.

REFERENCES

[0129] Bui T P N, Ritari J, Boeren S, de Waard P, Plugge C M, de Vos W M. (2015). Production of butyrate from lysine and the Amadori product fructoselysine by a human gut commensal. Nature Communication 6. [0130] Cox, J.; Mann, M. (2008). MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nature Biotechnology 26(12):1367-1372. [0131] Cox, N. Neuhauser, A. Michalski, R. A. Scheltema, J. V. Olsen and M. Mann (2011). Andromeda: A Peptide Search Engine Integrated into the MaxQuant. Environment. Journal of Proteome Research. 10(4): 1794-1805. [0132] Bielow, C., G. Mastrobuoni and S. Kempa (2016). Proteomics Quality Control: Quality Control Software for MaxQuant Results. Journal of Proteome Research 15(3): 777-787.

[0133] Beneficial Effect

[0134] It is known that dietary myo-inositol supplementation can reduce insulin resistance. The mechanism through which this occurs, however, is unknown. The present inventors considered that myo-inositol may have an indirect beneficial effect.

[0135] The present inventors envisaged that it is rather the metabolic conversion of myo-inositol that is beneficial to the host, rather than the myo-inositol itself. Hence, it is of interest to note that the production of butyrate and, notably, propionate, by A. rhamnosivorans is certainly beneficial for the patient (Hamer et al 2008 Pharmacology & Therapeutics 27: 104-119; Hosseini et al 2011 Nutrition Reviews 69: 245-258).

[0136] Hence, the supplementation of the patient with a bacterium according to the present disclosure, e.g. A. rhamnisovorans or alternatively both myo-inositol and A. rhamnosivorans provides a direct or synergistic effect on improved insulin resistance via additional propionate and butyrate production.

[0137] Treatment

[0138] Patients are treated as indicated below, according to the following 3 treatment arms: Treatment 1: 6 weeks, twice daily empty supplement.

[0139] Treatment 2: 6 weeks, twice daily supplement with 10.sup.8 living cells of a bacterium according to the present disclosure, i.e. A. rhamnisovorans.

[0140] Treatment 3: 6 weeks, twice daily supplement with 10.sup.8 living cells of a bacterium according to the present disclosure, i.e. A. rhamnisovorans in combination with 10 mg myo-inositol.

TABLE-US-00002 Effect Effect Effect No. of treatment 1 treatment 2 treatment 3 patients Condition (patient 1) (patient 2) (patient 3) 3 Insulin No effect Reduction Reduction of resistance of Insulin Insulin resistance resistance with with 10% 12.5%

[0141] It is expected that results similar to the putative effects as shown in the table above can be obtained with larger patient cohorts.

[0142] Other Host Bacteria

[0143] Another host bacterium, i.e. Escherichia coli is transfected according to standard methods with a gene set according to the present invention and comprising myo-inositol 2-dehydrogenase, inosose dehydratase, epi-inositol hydrolase, 5-deoxy-glucuronate isomerase, 5-keto-2-deoxygluconokinase, 5-keto-2-deoxy-D-gluconate-6 phosphate aldolase, glyceraldehyde-3-phosphate ketol-isomerase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, phosphoglycerate mutase, enolase, pyruvate kinase, pyruvate-flavodoxin oxidoreductase, 3-oxoacid CoA transferase. acyl-CoA dehydrogenase, enoyl-CoA hydratase, acryloyl-CoA dehydrogenase/Etf, and inosose isomerase. It is found that the host bacterium is capable of converting (myo)inositol to propionate under anaerobic conditions.