JP2019513392A5 - - Google Patents
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- JP2019513392A5 JP2019513392A5 JP2018553949A JP2018553949A JP2019513392A5 JP 2019513392 A5 JP2019513392 A5 JP 2019513392A5 JP 2018553949 A JP2018553949 A JP 2018553949A JP 2018553949 A JP2018553949 A JP 2018553949A JP 2019513392 A5 JP2019513392 A5 JP 2019513392A5
- Authority
- JP
- Japan
- Prior art keywords
- seq
- glucose
- steviol
- polypeptide
- amino acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- 108090000765 processed proteins & peptides Proteins 0.000 claims 102
- 229920001184 polypeptide Polymers 0.000 claims 101
- 102000004196 processed proteins & peptides Human genes 0.000 claims 101
- 239000004383 Steviol glycoside Substances 0.000 claims 87
- 229930182488 steviol glycoside Natural products 0.000 claims 87
- 235000019411 steviol glycoside Nutrition 0.000 claims 87
- 235000019202 steviosides Nutrition 0.000 claims 87
- 150000008144 steviol glycosides Chemical class 0.000 claims 83
- 239000008103 glucose Substances 0.000 claims 60
- 210000004027 cell Anatomy 0.000 claims 54
- 108090000623 proteins and genes Proteins 0.000 claims 54
- 125000003275 alpha amino acid group Chemical group 0.000 claims 52
- 239000000203 mixture Substances 0.000 claims 29
- 230000002194 synthesizing effect Effects 0.000 claims 27
- PGAVKCOVUIYSFO-XVFCMESISA-N UTP Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 PGAVKCOVUIYSFO-XVFCMESISA-N 0.000 claims 25
- PGAVKCOVUIYSFO-UHFFFAOYSA-N uridine-triphosphate Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)OC1N1C(=O)NC(=O)C=C1 PGAVKCOVUIYSFO-UHFFFAOYSA-N 0.000 claims 25
- HXXFSFRBOHSIMQ-VFUOTHLCSA-N alpha-D-glucose 1-phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(O)=O)[C@H](O)[C@@H](O)[C@@H]1O HXXFSFRBOHSIMQ-VFUOTHLCSA-N 0.000 claims 19
- 229950010772 glucose-1-phosphate Drugs 0.000 claims 19
- QFVOYBUQQBFCRH-UHFFFAOYSA-N Steviol Natural products C1CC2(C3)CC(=C)C3(O)CCC2C2(C)C1C(C)(C(O)=O)CCC2 QFVOYBUQQBFCRH-UHFFFAOYSA-N 0.000 claims 18
- QFVOYBUQQBFCRH-VQSWZGCSSA-N steviol Chemical compound C([C@@]1(O)C(=C)C[C@@]2(C1)CC1)C[C@H]2[C@@]2(C)[C@H]1[C@](C)(C(O)=O)CCC2 QFVOYBUQQBFCRH-VQSWZGCSSA-N 0.000 claims 18
- 229940032084 steviol Drugs 0.000 claims 18
- HSCJRCZFDFQWRP-JZMIEXBBSA-N UDP-alpha-D-glucose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OP(O)(=O)OP(O)(=O)OC[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C(NC(=O)C=C2)=O)O1 HSCJRCZFDFQWRP-JZMIEXBBSA-N 0.000 claims 17
- HSCJRCZFDFQWRP-UHFFFAOYSA-N Uridindiphosphoglukose Natural products OC1C(O)C(O)C(CO)OC1OP(O)(=O)OP(O)(=O)OCC1C(O)C(O)C(N2C(NC(=O)C=C2)=O)O1 HSCJRCZFDFQWRP-UHFFFAOYSA-N 0.000 claims 17
- 238000004113 cell culture Methods 0.000 claims 17
- RPYRMTHVSUWHSV-CUZJHZIBSA-N rebaudioside D Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O RPYRMTHVSUWHSV-CUZJHZIBSA-N 0.000 claims 16
- XCCTYIAWTASOJW-XVFCMESISA-N Uridine-5'-Diphosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 XCCTYIAWTASOJW-XVFCMESISA-N 0.000 claims 15
- 230000001279 glycosylating effect Effects 0.000 claims 14
- 238000000034 method Methods 0.000 claims 12
- NBSCHQHZLSJFNQ-GASJEMHNSA-N D-Glucose 6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@H]1O NBSCHQHZLSJFNQ-GASJEMHNSA-N 0.000 claims 9
- VFRROHXSMXFLSN-UHFFFAOYSA-N Glc6P Natural products OP(=O)(O)OCC(O)C(O)C(O)C(O)C=O VFRROHXSMXFLSN-UHFFFAOYSA-N 0.000 claims 9
- 241000544066 Stevia Species 0.000 claims 9
- 238000006206 glycosylation reaction Methods 0.000 claims 9
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 claims 9
- 230000013595 glycosylation Effects 0.000 claims 8
- QSRAJVGDWKFOGU-WBXIDTKBSA-N rebaudioside c Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]1(CC[C@H]2[C@@]3(C)[C@@H]([C@](CCC3)(C)C(=O)O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)CC3)C(=C)C[C@]23C1 QSRAJVGDWKFOGU-WBXIDTKBSA-N 0.000 claims 8
- DRSKVOAJKLUMCL-MMUIXFKXSA-N u2n4xkx7hp Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(O)=O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O DRSKVOAJKLUMCL-MMUIXFKXSA-N 0.000 claims 8
- 241000196324 Embryophyta Species 0.000 claims 7
- 239000001512 FEMA 4601 Substances 0.000 claims 6
- HELXLJCILKEWJH-SEAGSNCFSA-N Rebaudioside A Natural products O=C(O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@@]1(C)[C@@H]2[C@](C)([C@H]3[C@@]4(CC(=C)[C@@](O[C@H]5[C@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@H](O)[C@@H](CO)O5)(C4)CC3)CC2)CCC1 HELXLJCILKEWJH-SEAGSNCFSA-N 0.000 claims 6
- 150000001413 amino acids Chemical class 0.000 claims 6
- HELXLJCILKEWJH-UHFFFAOYSA-N entered according to Sigma 01432 Natural products C1CC2C3(C)CCCC(C)(C(=O)OC4C(C(O)C(O)C(CO)O4)O)C3CCC2(C2)CC(=C)C21OC(C1OC2C(C(O)C(O)C(CO)O2)O)OC(CO)C(O)C1OC1OC(CO)C(O)C(O)C1O HELXLJCILKEWJH-UHFFFAOYSA-N 0.000 claims 6
- 235000019203 rebaudioside A Nutrition 0.000 claims 6
- GSGVXNMGMKBGQU-PHESRWQRSA-N rebaudioside M Chemical compound C[C@@]12CCC[C@](C)([C@H]1CC[C@@]13CC(=C)[C@@](C1)(CC[C@@H]23)O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)[C@H]1O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O)C(=O)O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)[C@H]1O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O GSGVXNMGMKBGQU-PHESRWQRSA-N 0.000 claims 6
- -1 C-19 carboxyl group steviol glycoside Chemical class 0.000 claims 5
- 239000011541 reaction mixture Substances 0.000 claims 5
- OINNEUNVOZHBOX-QIRCYJPOSA-K 2-trans,6-trans,10-trans-geranylgeranyl diphosphate(3-) Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CC\C(C)=C\COP([O-])(=O)OP([O-])([O-])=O OINNEUNVOZHBOX-QIRCYJPOSA-K 0.000 claims 4
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 claims 4
- 239000001776 FEMA 4720 Substances 0.000 claims 4
- OINNEUNVOZHBOX-XBQSVVNOSA-N Geranylgeranyl diphosphate Natural products [P@](=O)(OP(=O)(O)O)(OC/C=C(\CC/C=C(\CC/C=C(\CC/C=C(\C)/C)/C)/C)/C)O OINNEUNVOZHBOX-XBQSVVNOSA-N 0.000 claims 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims 4
- RLLCWNUIHGPAJY-RYBZXKSASA-N Rebaudioside E Natural products O=C(O[C@H]1[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O2)[C@@H](O)[C@@H](O)[C@H](CO)O1)[C@]1(C)[C@@H]2[C@@](C)([C@@H]3[C@@]4(CC(=C)[C@@](O[C@@H]5[C@@H](O[C@@H]6[C@@H](O)[C@H](O)[C@@H](O)[C@H](CO)O6)[C@H](O)[C@@H](O)[C@H](CO)O5)(C4)CC3)CC2)CCC1 RLLCWNUIHGPAJY-RYBZXKSASA-N 0.000 claims 4
- NUHSROFQTUXZQQ-UHFFFAOYSA-N isopentenyl diphosphate Chemical compound CC(=C)CCO[P@](O)(=O)OP(O)(O)=O NUHSROFQTUXZQQ-UHFFFAOYSA-N 0.000 claims 4
- 229930188195 rebaudioside Natural products 0.000 claims 4
- RLLCWNUIHGPAJY-SFUUMPFESA-N rebaudioside E Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O RLLCWNUIHGPAJY-SFUUMPFESA-N 0.000 claims 4
- QRGRAFPOLJOGRV-UHFFFAOYSA-N rebaudioside F Natural products CC12CCCC(C)(C1CCC34CC(=C)C(CCC23)(C4)OC5OC(CO)C(O)C(OC6OCC(O)C(O)C6O)C5OC7OC(CO)C(O)C(O)C7O)C(=O)OC8OC(CO)C(O)C(O)C8O QRGRAFPOLJOGRV-UHFFFAOYSA-N 0.000 claims 4
- HYLAUKAHEAUVFE-AVBZULRRSA-N rebaudioside f Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)CO1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HYLAUKAHEAUVFE-AVBZULRRSA-N 0.000 claims 4
- 229940013618 stevioside Drugs 0.000 claims 4
- ONVABDHFQKWOSV-UHFFFAOYSA-N 16-Phyllocladene Natural products C1CC(C2)C(=C)CC32CCC2C(C)(C)CCCC2(C)C31 ONVABDHFQKWOSV-UHFFFAOYSA-N 0.000 claims 3
- 239000001177 diphosphate Substances 0.000 claims 3
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims 3
- 235000011180 diphosphates Nutrition 0.000 claims 3
- ONVABDHFQKWOSV-YQXATGRUSA-N ent-Kaur-16-ene Natural products C1C[C@@H](C2)C(=C)C[C@@]32CC[C@@H]2C(C)(C)CCC[C@@]2(C)[C@@H]31 ONVABDHFQKWOSV-YQXATGRUSA-N 0.000 claims 3
- NIKHGUQULKYIGE-SHAPNJEPSA-N ent-kaur-16-en-19-oic acid Chemical compound C([C@H]1C[C@]2(CC1=C)CC1)C[C@H]2[C@@]2(C)[C@H]1[C@](C)(C(O)=O)CCC2 NIKHGUQULKYIGE-SHAPNJEPSA-N 0.000 claims 3
- KWVKUAKMOIEELN-UHFFFAOYSA-N ent-kaur-16-en-19-oic acid Natural products CC1(C)CCCC2(C)C1CCC34CC(=C(C3)C(=O)O)CCC24 KWVKUAKMOIEELN-UHFFFAOYSA-N 0.000 claims 3
- ONVABDHFQKWOSV-HPUSYDDDSA-N ent-kaur-16-ene Chemical compound C1C[C@H](C2)C(=C)C[C@@]32CC[C@@H]2C(C)(C)CCC[C@@]2(C)[C@@H]31 ONVABDHFQKWOSV-HPUSYDDDSA-N 0.000 claims 3
- UIXMIBNGPQGJJJ-UHFFFAOYSA-N ent-kaurene Natural products CC1CC23CCC4C(CCCC4(C)C)C2CCC1C3 UIXMIBNGPQGJJJ-UHFFFAOYSA-N 0.000 claims 3
- NIKHGUQULKYIGE-UHFFFAOYSA-N kaurenoic acid Natural products C1CC2(CC3=C)CC3CCC2C2(C)C1C(C)(C(O)=O)CCC2 NIKHGUQULKYIGE-UHFFFAOYSA-N 0.000 claims 3
- 238000004519 manufacturing process Methods 0.000 claims 3
- 239000006228 supernatant Substances 0.000 claims 3
- VWFJDQUYCIWHTN-YFVJMOTDSA-N 2-trans,6-trans-farnesyl diphosphate Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CO[P@](O)(=O)OP(O)(O)=O VWFJDQUYCIWHTN-YFVJMOTDSA-N 0.000 claims 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 claims 2
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 claims 2
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 claims 2
- VWFJDQUYCIWHTN-FBXUGWQNSA-N Farnesyl diphosphate Natural products CC(C)=CCC\C(C)=C/CC\C(C)=C/COP(O)(=O)OP(O)(O)=O VWFJDQUYCIWHTN-FBXUGWQNSA-N 0.000 claims 2
- 229930091371 Fructose Natural products 0.000 claims 2
- 239000005715 Fructose Substances 0.000 claims 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims 2
- 241000238631 Hexapoda Species 0.000 claims 2
- SHZGCJCMOBCMKK-JFNONXLTSA-N L-rhamnopyranose Chemical compound C[C@@H]1OC(O)[C@H](O)[C@H](O)[C@H]1O SHZGCJCMOBCMKK-JFNONXLTSA-N 0.000 claims 2
- PNNNRSAQSRJVSB-UHFFFAOYSA-N L-rhamnose Natural products CC(O)C(O)C(O)C(O)C=O PNNNRSAQSRJVSB-UHFFFAOYSA-N 0.000 claims 2
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 claims 2
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 claims 2
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 claims 2
- YWPVROCHNBYFTP-UHFFFAOYSA-N Rubusoside Natural products C1CC2C3(C)CCCC(C)(C(=O)OC4C(C(O)C(O)C(CO)O4)O)C3CCC2(C2)CC(=C)C21OC1OC(CO)C(O)C(O)C1O YWPVROCHNBYFTP-UHFFFAOYSA-N 0.000 claims 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims 2
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- DQQDLYVHOTZLOR-OCIMBMBZSA-N UDP-alpha-D-xylose Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C(NC(=O)C=C1)=O)O)O)OP(O)(=O)OP(O)(=O)O[C@H]1OC[C@@H](O)[C@H](O)[C@H]1O DQQDLYVHOTZLOR-OCIMBMBZSA-N 0.000 claims 2
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- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 claims 2
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- 239000013592 cell lysate Substances 0.000 claims 2
- 230000002538 fungal effect Effects 0.000 claims 2
- 229930182470 glycoside Natural products 0.000 claims 2
- 150000002338 glycosides Chemical class 0.000 claims 2
- 210000004962 mammalian cell Anatomy 0.000 claims 2
- 229910052751 metal Inorganic materials 0.000 claims 2
- 239000002184 metal Substances 0.000 claims 2
- 150000002739 metals Chemical class 0.000 claims 2
- 229950006780 n-acetylglucosamine Drugs 0.000 claims 2
- 235000015097 nutrients Nutrition 0.000 claims 2
- YWPVROCHNBYFTP-OSHKXICASA-N rubusoside Chemical compound O([C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O YWPVROCHNBYFTP-OSHKXICASA-N 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 2
- QSIDJGUAAUSPMG-CULFPKEHSA-N steviolmonoside Chemical compound O([C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(O)=O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O QSIDJGUAAUSPMG-CULFPKEHSA-N 0.000 claims 2
- 239000005720 sucrose Substances 0.000 claims 2
- OQPOFZJZPYRNFF-CULFPKEHSA-N tkd5uc898q Chemical compound O=C([C@]1(C)CCC[C@@]2([C@@H]1CC[C@]13C[C@](O)(C(=C)C1)CC[C@@H]23)C)O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O OQPOFZJZPYRNFF-CULFPKEHSA-N 0.000 claims 2
- 235000013343 vitamin Nutrition 0.000 claims 2
- 229940088594 vitamin Drugs 0.000 claims 2
- 229930003231 vitamin Natural products 0.000 claims 2
- 239000011782 vitamin Substances 0.000 claims 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims 1
- 230000036983 biotransformation Effects 0.000 claims 1
- 239000006143 cell culture medium Substances 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 238000004255 ion exchange chromatography Methods 0.000 claims 1
- 238000002955 isolation Methods 0.000 claims 1
- 239000007791 liquid phase Substances 0.000 claims 1
- 229910052757 nitrogen Inorganic materials 0.000 claims 1
- 230000001737 promoting effect Effects 0.000 claims 1
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2017
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- 2017-04-13 BR BR112018071144-6A patent/BR112018071144B1/pt active IP Right Grant
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2021
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