JP2022159411A - アルデヒドデヒドロゲナーゼバリアントおよび使用の方法 - Google Patents
アルデヒドデヒドロゲナーゼバリアントおよび使用の方法 Download PDFInfo
- Publication number
- JP2022159411A JP2022159411A JP2022127874A JP2022127874A JP2022159411A JP 2022159411 A JP2022159411 A JP 2022159411A JP 2022127874 A JP2022127874 A JP 2022127874A JP 2022127874 A JP2022127874 A JP 2022127874A JP 2022159411 A JP2022159411 A JP 2022159411A
- Authority
- JP
- Japan
- Prior art keywords
- bdo
- hbal
- coa
- amino acid
- cells
- 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
Links
- 102000005369 Aldehyde Dehydrogenase Human genes 0.000 title abstract description 203
- 108020002663 Aldehyde Dehydrogenase Proteins 0.000 title abstract description 203
- 238000000034 method Methods 0.000 title abstract description 176
- HSJKGGMUJITCBW-UHFFFAOYSA-N 3-hydroxybutanal Chemical compound CC(O)CC=O HSJKGGMUJITCBW-UHFFFAOYSA-N 0.000 abstract description 610
- AXPZIVKEZRHGAS-UHFFFAOYSA-N 3-benzyl-5-[(2-nitrophenoxy)methyl]oxolan-2-one Chemical compound [O-][N+](=O)C1=CC=CC=C1OCC1OC(=O)C(CC=2C=CC=CC=2)C1 AXPZIVKEZRHGAS-UHFFFAOYSA-N 0.000 abstract description 277
- PIAOXUVIBAKVSP-UHFFFAOYSA-N γ-hydroxybutyraldehyde Chemical compound OCCCC=O PIAOXUVIBAKVSP-UHFFFAOYSA-N 0.000 abstract description 272
- 150000007523 nucleic acids Chemical class 0.000 abstract description 191
- 102000039446 nucleic acids Human genes 0.000 abstract description 170
- 108020004707 nucleic acids Proteins 0.000 abstract description 170
- 229920001184 polypeptide Polymers 0.000 abstract description 159
- 108090000765 processed proteins & peptides Proteins 0.000 abstract description 159
- 102000004196 processed proteins & peptides Human genes 0.000 abstract description 159
- 150000002148 esters Chemical class 0.000 abstract description 136
- 150000001408 amides Chemical class 0.000 abstract description 129
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 abstract description 88
- WERYXYBDKMZEQL-UHFFFAOYSA-N butane-1,4-diol Chemical compound OCCCCO WERYXYBDKMZEQL-UHFFFAOYSA-N 0.000 abstract description 68
- 238000012258 culturing Methods 0.000 abstract description 8
- 239000006166 lysate Substances 0.000 abstract description 6
- 239000000047 product Substances 0.000 description 305
- 210000004027 cell Anatomy 0.000 description 273
- 125000003275 alpha amino acid group Chemical group 0.000 description 199
- 235000001014 amino acid Nutrition 0.000 description 179
- 108090000623 proteins and genes Proteins 0.000 description 177
- 230000037361 pathway Effects 0.000 description 133
- 102000004190 Enzymes Human genes 0.000 description 125
- 108090000790 Enzymes Proteins 0.000 description 125
- 238000006467 substitution reaction Methods 0.000 description 121
- -1 3-hydroxybutyl Chemical group 0.000 description 78
- 238000006243 chemical reaction Methods 0.000 description 77
- 230000000694 effects Effects 0.000 description 76
- 102000004169 proteins and genes Human genes 0.000 description 74
- 235000018102 proteins Nutrition 0.000 description 69
- KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical compound C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 68
- ZSLZBFCDCINBPY-ZSJPKINUSA-N acetyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZSLZBFCDCINBPY-ZSJPKINUSA-N 0.000 description 62
- 238000004519 manufacturing process Methods 0.000 description 62
- 239000000758 substrate Substances 0.000 description 61
- 239000000543 intermediate Substances 0.000 description 55
- BAMBWCGEVIAQBF-CITAKDKDSA-N 4-hydroxybutyryl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CCCO)O[C@H]1N1C2=NC=NC(N)=C2N=C1 BAMBWCGEVIAQBF-CITAKDKDSA-N 0.000 description 50
- 229920001791 ((R)-3-Hydroxybutanoyl)(n-2) Polymers 0.000 description 45
- QHHKKMYHDBRONY-RMNRSTNRSA-N 3-hydroxybutanoyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CC(O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 QHHKKMYHDBRONY-RMNRSTNRSA-N 0.000 description 45
- 150000001413 amino acids Chemical class 0.000 description 45
- 238000000855 fermentation Methods 0.000 description 44
- 229940024606 amino acid Drugs 0.000 description 43
- 230000004151 fermentation Effects 0.000 description 43
- 230000015572 biosynthetic process Effects 0.000 description 42
- 229910052799 carbon Inorganic materials 0.000 description 42
- 230000014509 gene expression Effects 0.000 description 42
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 41
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 41
- 235000019437 butane-1,3-diol Nutrition 0.000 description 41
- 102000004316 Oxidoreductases Human genes 0.000 description 34
- 108090000854 Oxidoreductases Proteins 0.000 description 34
- 238000000338 in vitro Methods 0.000 description 33
- 241000894007 species Species 0.000 description 33
- 230000001965 increasing effect Effects 0.000 description 32
- 239000000203 mixture Substances 0.000 description 32
- 229920001707 polybutylene terephthalate Polymers 0.000 description 32
- 229920002791 poly-4-hydroxybutyrate Polymers 0.000 description 31
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 30
- 229920002334 Spandex Polymers 0.000 description 28
- 230000012010 growth Effects 0.000 description 27
- 239000013592 cell lysate Substances 0.000 description 26
- 150000001875 compounds Chemical class 0.000 description 25
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 24
- 230000006696 biosynthetic metabolic pathway Effects 0.000 description 24
- 230000002503 metabolic effect Effects 0.000 description 24
- 239000000126 substance Substances 0.000 description 24
- 230000000813 microbial effect Effects 0.000 description 23
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 22
- 239000002609 medium Substances 0.000 description 22
- 239000003208 petroleum Substances 0.000 description 22
- 239000013598 vector Substances 0.000 description 22
- 238000000926 separation method Methods 0.000 description 21
- 230000006870 function Effects 0.000 description 20
- 230000035772 mutation Effects 0.000 description 20
- 239000006227 byproduct Substances 0.000 description 19
- 229920002635 polyurethane Polymers 0.000 description 19
- 239000004814 polyurethane Substances 0.000 description 19
- 230000037430 deletion Effects 0.000 description 17
- 210000004177 elastic tissue Anatomy 0.000 description 17
- 238000009396 hybridization Methods 0.000 description 17
- 229920001778 nylon Polymers 0.000 description 17
- 229920003023 plastic Polymers 0.000 description 17
- 239000004033 plastic Substances 0.000 description 17
- 229920002396 Polyurea Polymers 0.000 description 16
- 229920001577 copolymer Polymers 0.000 description 16
- 238000012217 deletion Methods 0.000 description 16
- 238000002703 mutagenesis Methods 0.000 description 16
- 231100000350 mutagenesis Toxicity 0.000 description 16
- 239000003960 organic solvent Substances 0.000 description 16
- 229920001225 polyester resin Polymers 0.000 description 16
- 239000004645 polyester resin Substances 0.000 description 16
- 239000002243 precursor Substances 0.000 description 16
- 101710088194 Dehydrogenase Proteins 0.000 description 15
- 150000001299 aldehydes Chemical class 0.000 description 15
- 239000003472 antidiabetic agent Substances 0.000 description 15
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 15
- 229940126904 hypoglycaemic agent Drugs 0.000 description 15
- 239000005014 poly(hydroxyalkanoate) Substances 0.000 description 15
- 229920000728 polyester Polymers 0.000 description 15
- 229920000903 polyhydroxyalkanoate Polymers 0.000 description 15
- 229920005749 polyurethane resin Polymers 0.000 description 15
- 230000008569 process Effects 0.000 description 15
- 108091028043 Nucleic acid sequence Proteins 0.000 description 14
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 14
- 229920003224 poly(trimethylene oxide) Polymers 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- 239000004759 spandex Substances 0.000 description 14
- SJZRECIVHVDYJC-UHFFFAOYSA-M 4-hydroxybutyrate Chemical compound OCCCC([O-])=O SJZRECIVHVDYJC-UHFFFAOYSA-M 0.000 description 13
- 230000002255 enzymatic effect Effects 0.000 description 13
- 239000000463 material Substances 0.000 description 13
- 244000005700 microbiome Species 0.000 description 13
- 230000002829 reductive effect Effects 0.000 description 13
- 241000894006 Bacteria Species 0.000 description 12
- OKTJSMMVPCPJKN-IGMARMGPSA-N Carbon-12 Chemical compound [12C] OKTJSMMVPCPJKN-IGMARMGPSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 12
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- HSJKGGMUJITCBW-SCSAIBSYSA-N (3r)-3-hydroxybutanal Chemical compound C[C@@H](O)CC=O HSJKGGMUJITCBW-SCSAIBSYSA-N 0.000 description 11
- SYTBZMRGLBWNTM-SNVBAGLBSA-N (R)-flurbiprofen Chemical class FC1=CC([C@H](C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-SNVBAGLBSA-N 0.000 description 11
- OKTJSMMVPCPJKN-OUBTZVSYSA-N Carbon-13 Chemical compound [13C] OKTJSMMVPCPJKN-OUBTZVSYSA-N 0.000 description 11
- 230000001851 biosynthetic effect Effects 0.000 description 11
- 229910002092 carbon dioxide Inorganic materials 0.000 description 11
- 230000004077 genetic alteration Effects 0.000 description 11
- 231100000118 genetic alteration Toxicity 0.000 description 11
- 230000001976 improved effect Effects 0.000 description 11
- 238000010348 incorporation Methods 0.000 description 11
- 230000006680 metabolic alteration Effects 0.000 description 11
- 230000001105 regulatory effect Effects 0.000 description 11
- 108020004414 DNA Proteins 0.000 description 10
- OJFDKHTZOUZBOS-CITAKDKDSA-N acetoacetyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CC(=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 OJFDKHTZOUZBOS-CITAKDKDSA-N 0.000 description 10
- 210000000349 chromosome Anatomy 0.000 description 10
- 239000013604 expression vector Substances 0.000 description 10
- 238000012224 gene deletion Methods 0.000 description 10
- 239000001301 oxygen Substances 0.000 description 10
- 229910052760 oxygen Inorganic materials 0.000 description 10
- 239000013612 plasmid Substances 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
- 239000002028 Biomass Substances 0.000 description 9
- 241000588724 Escherichia coli Species 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 9
- 239000012298 atmosphere Substances 0.000 description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 9
- 238000004422 calculation algorithm Methods 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 9
- 230000004048 modification Effects 0.000 description 9
- 238000012986 modification Methods 0.000 description 9
- 230000009467 reduction Effects 0.000 description 9
- 238000013518 transcription Methods 0.000 description 9
- 230000035897 transcription Effects 0.000 description 9
- PUPZLCDOIYMWBV-SCSAIBSYSA-N (R)-butane-1,3-diol Chemical compound C[C@@H](O)CCO PUPZLCDOIYMWBV-SCSAIBSYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 210000003527 eukaryotic cell Anatomy 0.000 description 8
- 239000004615 ingredient Substances 0.000 description 8
- 230000037353 metabolic pathway Effects 0.000 description 8
- 238000006241 metabolic reaction Methods 0.000 description 8
- 239000000376 reactant Substances 0.000 description 8
- 230000009466 transformation Effects 0.000 description 8
- 238000013519 translation Methods 0.000 description 8
- 230000014616 translation Effects 0.000 description 8
- HSJKGGMUJITCBW-BYPYZUCNSA-N (3s)-3-hydroxybutanal Chemical compound C[C@H](O)CC=O HSJKGGMUJITCBW-BYPYZUCNSA-N 0.000 description 7
- LVSQXDHWDCMMRJ-UHFFFAOYSA-N 4-hydroxybutan-2-one Chemical compound CC(=O)CCO LVSQXDHWDCMMRJ-UHFFFAOYSA-N 0.000 description 7
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 7
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 7
- 102000004357 Transferases Human genes 0.000 description 7
- 108090000992 Transferases Proteins 0.000 description 7
- 238000007792 addition Methods 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 239000011942 biocatalyst Substances 0.000 description 7
- 235000010633 broth Nutrition 0.000 description 7
- 150000001720 carbohydrates Chemical class 0.000 description 7
- 235000014633 carbohydrates Nutrition 0.000 description 7
- 230000004907 flux Effects 0.000 description 7
- 230000001939 inductive effect Effects 0.000 description 7
- 239000002773 nucleotide Substances 0.000 description 7
- 125000003729 nucleotide group Chemical group 0.000 description 7
- 238000005457 optimization Methods 0.000 description 7
- XGAWKWCCTIEGRI-UHFFFAOYSA-N phosphono 4-hydroxybutanoate Chemical compound OCCCC(=O)OP(O)(O)=O XGAWKWCCTIEGRI-UHFFFAOYSA-N 0.000 description 7
- 238000004088 simulation Methods 0.000 description 7
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 102000053602 DNA Human genes 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 108020002908 Epoxide hydrolase Proteins 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 6
- KKEYFWRCBNTPAC-UHFFFAOYSA-N Terephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 230000004075 alteration Effects 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 238000003776 cleavage reaction Methods 0.000 description 6
- 239000002537 cosmetic Substances 0.000 description 6
- 238000013461 design Methods 0.000 description 6
- 235000013305 food Nutrition 0.000 description 6
- 239000003205 fragrance Substances 0.000 description 6
- 239000007789 gas Substances 0.000 description 6
- 230000002068 genetic effect Effects 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 230000003834 intracellular effect Effects 0.000 description 6
- 230000000155 isotopic effect Effects 0.000 description 6
- 150000002576 ketones Chemical class 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 102000040430 polynucleotide Human genes 0.000 description 6
- 108091033319 polynucleotide Proteins 0.000 description 6
- 239000002157 polynucleotide Substances 0.000 description 6
- 230000006798 recombination Effects 0.000 description 6
- 230000007017 scission Effects 0.000 description 6
- 238000002864 sequence alignment Methods 0.000 description 6
- UIUJIQZEACWQSV-UHFFFAOYSA-N succinic semialdehyde Chemical compound OC(=O)CCC=O UIUJIQZEACWQSV-UHFFFAOYSA-N 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- QHHKKMYHDBRONY-WZZMXTMRSA-N (R)-3-hydroxybutanoyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@H](O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 QHHKKMYHDBRONY-WZZMXTMRSA-N 0.000 description 5
- 108091035707 Consensus sequence Proteins 0.000 description 5
- 102000005486 Epoxide hydrolase Human genes 0.000 description 5
- 241000206602 Eukaryota Species 0.000 description 5
- 241000282414 Homo sapiens Species 0.000 description 5
- 239000004677 Nylon Substances 0.000 description 5
- 108091000080 Phosphotransferase Proteins 0.000 description 5
- 108010084086 Succinate-Semialdehyde Dehydrogenase Proteins 0.000 description 5
- 102000005566 Succinate-Semialdehyde Dehydrogenase Human genes 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 230000002950 deficient Effects 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 102000020233 phosphotransferase Human genes 0.000 description 5
- 238000003752 polymerase chain reaction Methods 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 238000005215 recombination Methods 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 230000008685 targeting Effects 0.000 description 5
- TZBGSHAFWLGWBO-ABLWVSNPSA-N (2s)-2-[[4-[(2-amino-4-oxo-5,6,7,8-tetrahydro-1h-pteridin-6-yl)methylamino]benzoyl]amino]-5-methoxy-5-oxopentanoic acid Chemical compound C1=CC(C(=O)N[C@@H](CCC(=O)OC)C(O)=O)=CC=C1NCC1NC(C(=O)NC(N)=N2)=C2NC1 TZBGSHAFWLGWBO-ABLWVSNPSA-N 0.000 description 4
- QHHKKMYHDBRONY-VKBDFPRVSA-N (S)-3-hydroxybutanoyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@@H](O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 QHHKKMYHDBRONY-VKBDFPRVSA-N 0.000 description 4
- SVTBMSDMJJWYQN-UHFFFAOYSA-N 2-methylpentane-2,4-diol Chemical compound CC(O)CC(C)(C)O SVTBMSDMJJWYQN-UHFFFAOYSA-N 0.000 description 4
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 4
- 108010093796 4-hydroxybutyrate dehydrogenase Proteins 0.000 description 4
- 102220491082 ADP-ribosylation factor 6_D12A_mutation Human genes 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 4
- 108010074122 Ferredoxins Proteins 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- 241000233866 Fungi Species 0.000 description 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 description 4
- 102000005720 Glutathione transferase Human genes 0.000 description 4
- 108010070675 Glutathione transferase Proteins 0.000 description 4
- 102000003960 Ligases Human genes 0.000 description 4
- 108090000364 Ligases Proteins 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- 241000605862 Porphyromonas gingivalis Species 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 4
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 4
- 108010031234 carbon monoxide dehydrogenase Proteins 0.000 description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
- 230000002759 chromosomal effect Effects 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- 238000000205 computational method Methods 0.000 description 4
- 239000012228 culture supernatant Substances 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- 239000012467 final product Substances 0.000 description 4
- 239000000796 flavoring agent Substances 0.000 description 4
- 238000012239 gene modification Methods 0.000 description 4
- 230000005017 genetic modification Effects 0.000 description 4
- 235000013617 genetically modified food Nutrition 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 230000010354 integration Effects 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 238000010369 molecular cloning Methods 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 235000015097 nutrients Nutrition 0.000 description 4
- 239000013520 petroleum-based product Substances 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 238000000638 solvent extraction Methods 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- VNOYUJKHFWYWIR-ITIYDSSPSA-N succinyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CCC(O)=O)O[C@H]1N1C2=NC=NC(N)=C2N=C1 VNOYUJKHFWYWIR-ITIYDSSPSA-N 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- UIKQNMXWCYQNCS-UHFFFAOYSA-N 2-hydroxybutanal Chemical compound CCC(O)C=O UIKQNMXWCYQNCS-UHFFFAOYSA-N 0.000 description 3
- KPGXRSRHYNQIFN-UHFFFAOYSA-L 2-oxoglutarate(2-) Chemical compound [O-]C(=O)CCC(=O)C([O-])=O KPGXRSRHYNQIFN-UHFFFAOYSA-L 0.000 description 3
- 241000203069 Archaea Species 0.000 description 3
- 241001465318 Aspergillus terreus Species 0.000 description 3
- 244000063299 Bacillus subtilis Species 0.000 description 3
- 235000014469 Bacillus subtilis Nutrition 0.000 description 3
- 241000193401 Clostridium acetobutylicum Species 0.000 description 3
- 241001508458 Clostridium saccharoperbutylacetonicum Species 0.000 description 3
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 3
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 108060002716 Exonuclease Proteins 0.000 description 3
- 241000605986 Fusobacterium nucleatum Species 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000238631 Hexapoda Species 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 108010020056 Hydrogenase Proteins 0.000 description 3
- 102000004157 Hydrolases Human genes 0.000 description 3
- 108090000604 Hydrolases Proteins 0.000 description 3
- 241001138401 Kluyveromyces lactis Species 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- 102000016387 Pancreatic elastase Human genes 0.000 description 3
- 108010067372 Pancreatic elastase Proteins 0.000 description 3
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 3
- 241000589776 Pseudomonas putida Species 0.000 description 3
- 241000235347 Schizosaccharomyces pombe Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 108091000039 acetoacetyl-CoA reductase Proteins 0.000 description 3
- 230000003698 anagen phase Effects 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 229960003237 betaine Drugs 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 238000010924 continuous production Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000009483 enzymatic pathway Effects 0.000 description 3
- 238000006911 enzymatic reaction Methods 0.000 description 3
- 102000013165 exonuclease Human genes 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000002803 fossil fuel Substances 0.000 description 3
- 238000002309 gasification Methods 0.000 description 3
- 235000021472 generally recognized as safe Nutrition 0.000 description 3
- 229930195712 glutamate Natural products 0.000 description 3
- 229940049906 glutamate Drugs 0.000 description 3
- GOQYKNQRPGWPLP-UHFFFAOYSA-N heptadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 238000000622 liquid--liquid extraction Methods 0.000 description 3
- 238000004949 mass spectrometry Methods 0.000 description 3
- 230000003278 mimic effect Effects 0.000 description 3
- 238000003032 molecular docking Methods 0.000 description 3
- 239000003471 mutagenic agent Substances 0.000 description 3
- 230000002018 overexpression Effects 0.000 description 3
- 235000006408 oxalic acid Nutrition 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 230000002335 preservative effect Effects 0.000 description 3
- 210000001236 prokaryotic cell Anatomy 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical compound C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-N 0.000 description 2
- AZPQKDMBANNLMJ-AENDTGMFSA-N (3r)-3-hydroxybutanoic acid;propane-1,2,3-triol Chemical compound OCC(O)CO.C[C@@H](O)CC(O)=O AZPQKDMBANNLMJ-AENDTGMFSA-N 0.000 description 2
- PSBDWGZCVUAZQS-UHFFFAOYSA-N (dimethylsulfonio)acetate Chemical compound C[S+](C)CC([O-])=O PSBDWGZCVUAZQS-UHFFFAOYSA-N 0.000 description 2
- YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- BBMCTIGTTCKYKF-UHFFFAOYSA-N 1-heptanol Chemical compound CCCCCCCO BBMCTIGTTCKYKF-UHFFFAOYSA-N 0.000 description 2
- 108010021680 2-oxoglutarate decarboxylase Proteins 0.000 description 2
- KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical compound OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 description 2
- 108010055682 3-hydroxybutyryl-CoA dehydrogenase Proteins 0.000 description 2
- PKQIDSVLSKFZQC-UHFFFAOYSA-N 3-oxobutanal Chemical compound CC(=O)CC=O PKQIDSVLSKFZQC-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 241000193451 Acetoanaerobium sticklandii Species 0.000 description 2
- 108010006229 Acetyl-CoA C-acetyltransferase Proteins 0.000 description 2
- 102000005345 Acetyl-CoA C-acetyltransferase Human genes 0.000 description 2
- 241000604450 Acidaminococcus fermentans Species 0.000 description 2
- 108010021809 Alcohol dehydrogenase Proteins 0.000 description 2
- 102000007698 Alcohol dehydrogenase Human genes 0.000 description 2
- 108020004306 Alpha-ketoglutarate dehydrogenase Proteins 0.000 description 2
- 102000006589 Alpha-ketoglutarate dehydrogenase Human genes 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 241000219195 Arabidopsis thaliana Species 0.000 description 2
- 241000205042 Archaeoglobus fulgidus Species 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 241000228245 Aspergillus niger Species 0.000 description 2
- 101000695175 Bacillus subtilis (strain 168) Probable phosphate butyryltransferase Proteins 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 108700024126 Butyrate kinases Proteins 0.000 description 2
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 2
- 241000193403 Clostridium Species 0.000 description 2
- 241000193454 Clostridium beijerinckii Species 0.000 description 2
- 241000193155 Clostridium botulinum Species 0.000 description 2
- 241000186570 Clostridium kluyveri Species 0.000 description 2
- RGJOEKWQDUBAIZ-IBOSZNHHSA-N CoASH Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS)O[C@H]1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-IBOSZNHHSA-N 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 108020004635 Complementary DNA Proteins 0.000 description 2
- 241000186226 Corynebacterium glutamicum Species 0.000 description 2
- 241000252867 Cupriavidus metallidurans Species 0.000 description 2
- 241000414116 Cyanobium Species 0.000 description 2
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 2
- 102000052510 DNA-Binding Proteins Human genes 0.000 description 2
- 108700020911 DNA-Binding Proteins Proteins 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical group COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 2
- 102100025413 Formyltetrahydrofolate synthetase Human genes 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 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 description 2
- 239000005715 Fructose Substances 0.000 description 2
- 241000605909 Fusobacterium Species 0.000 description 2
- 241000626621 Geobacillus Species 0.000 description 2
- 108091022930 Glutamate decarboxylase Proteins 0.000 description 2
- 102000008214 Glutamate decarboxylase Human genes 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000205063 Haloarcula marismortui Species 0.000 description 2
- 102100039894 Hemoglobin subunit delta Human genes 0.000 description 2
- 102000006947 Histones Human genes 0.000 description 2
- 108010033040 Histones Proteins 0.000 description 2
- 241000588749 Klebsiella oxytoca Species 0.000 description 2
- 241000588747 Klebsiella pneumoniae Species 0.000 description 2
- 241000235058 Komagataella pastoris Species 0.000 description 2
- 241000235087 Lachancea kluyveri Species 0.000 description 2
- 240000006024 Lactobacillus plantarum Species 0.000 description 2
- 235000013965 Lactobacillus plantarum Nutrition 0.000 description 2
- 241000192130 Leuconostoc mesenteroides Species 0.000 description 2
- 102000004882 Lipase Human genes 0.000 description 2
- 108090001060 Lipase Proteins 0.000 description 2
- 239000004367 Lipase Substances 0.000 description 2
- 241000157876 Metallosphaera sedula Species 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 241000186366 Mycobacterium bovis Species 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 244000061176 Nicotiana tabacum Species 0.000 description 2
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 2
- 241001197104 Nocardia iowensis Species 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 241000228150 Penicillium chrysogenum Species 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- 241000589516 Pseudomonas Species 0.000 description 2
- 241000589540 Pseudomonas fluorescens Species 0.000 description 2
- 241000589614 Pseudomonas stutzeri Species 0.000 description 2
- 241000736843 Pyrobaculum aerophilum Species 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 2
- 241000700157 Rattus norvegicus Species 0.000 description 2
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 2
- 102000012479 Serine Proteases Human genes 0.000 description 2
- 108010022999 Serine Proteases Proteins 0.000 description 2
- 108010090804 Streptavidin Proteins 0.000 description 2
- 244000057717 Streptococcus lactis Species 0.000 description 2
- 235000014897 Streptococcus lactis Nutrition 0.000 description 2
- 101710172711 Structural protein Proteins 0.000 description 2
- 102000011929 Succinate-CoA Ligases Human genes 0.000 description 2
- 108010075728 Succinate-CoA Ligases Proteins 0.000 description 2
- 241000205098 Sulfolobus acidocaldarius Species 0.000 description 2
- 241000160715 Sulfolobus tokodaii Species 0.000 description 2
- 241000589499 Thermus thermophilus Species 0.000 description 2
- 102000003929 Transaminases Human genes 0.000 description 2
- 108090000340 Transaminases Proteins 0.000 description 2
- 241000223105 Trypanosoma brucei Species 0.000 description 2
- 241000588902 Zymomonas mobilis Species 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 238000004760 accelerator mass spectrometry Methods 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 2
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 238000000137 annealing Methods 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- 239000004599 antimicrobial Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N aspartic acid group Chemical group N[C@@H](CC(=O)O)C(=O)O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 238000012219 cassette mutagenesis Methods 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 239000013611 chromosomal DNA Substances 0.000 description 2
- 239000003245 coal Substances 0.000 description 2
- RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 2
- 239000005516 coenzyme A Substances 0.000 description 2
- 229940093530 coenzyme a Drugs 0.000 description 2
- 230000021615 conjugation Effects 0.000 description 2
- 238000012937 correction Methods 0.000 description 2
- 239000000490 cosmetic additive Substances 0.000 description 2
- 239000008406 cosmetic ingredient Substances 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000012136 culture method Methods 0.000 description 2
- 230000009615 deamination Effects 0.000 description 2
- 238000006481 deamination reaction Methods 0.000 description 2
- MWKFXSUHUHTGQN-UHFFFAOYSA-N decan-1-ol Chemical compound CCCCCCCCCCO MWKFXSUHUHTGQN-UHFFFAOYSA-N 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 150000005690 diesters Chemical class 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 2
- SZXQTJUDPRGNJN-UHFFFAOYSA-N dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 239000003974 emollient agent Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 238000010799 enzyme reaction rate Methods 0.000 description 2
- 230000001815 facial effect Effects 0.000 description 2
- 239000012526 feed medium Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 235000013373 food additive Nutrition 0.000 description 2
- 239000002778 food additive Substances 0.000 description 2
- 235000012041 food component Nutrition 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 239000005417 food ingredient Substances 0.000 description 2
- 235000019256 formaldehyde Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 229930182830 galactose Natural products 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- 239000008266 hair spray Substances 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 229940051250 hexylene glycol Drugs 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- BTFJIXJJCSYFAL-UHFFFAOYSA-N icosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCO BTFJIXJJCSYFAL-UHFFFAOYSA-N 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 238000004255 ion exchange chromatography Methods 0.000 description 2
- 229940072205 lactobacillus plantarum Drugs 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 235000019421 lipase Nutrition 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000004066 metabolic change Effects 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 210000003470 mitochondria Anatomy 0.000 description 2
- 230000002438 mitochondrial effect Effects 0.000 description 2
- 230000003020 moisturizing effect Effects 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 2
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 2
- XGFDHKJUZCCPKQ-UHFFFAOYSA-N nonadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCO XGFDHKJUZCCPKQ-UHFFFAOYSA-N 0.000 description 2
- ZWRUINPWMLAQRD-UHFFFAOYSA-N nonan-1-ol Chemical compound CCCCCCCCCO ZWRUINPWMLAQRD-UHFFFAOYSA-N 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 239000002417 nutraceutical Substances 0.000 description 2
- 235000021436 nutraceutical agent Nutrition 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 230000008723 osmotic stress Effects 0.000 description 2
- REIUXOLGHVXAEO-UHFFFAOYSA-N pentadecan-1-ol Chemical compound CCCCCCCCCCCCCCCO REIUXOLGHVXAEO-UHFFFAOYSA-N 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- 238000010647 peptide synthesis reaction Methods 0.000 description 2
- 125000005642 phosphothioate group Chemical group 0.000 description 2
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000037452 priming Effects 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 239000012925 reference material Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 239000001488 sodium phosphate Substances 0.000 description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 238000001546 stable isotope ratio mass spectrometry Methods 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 description 2
- HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 2
- 231100000027 toxicology Toxicity 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 238000000844 transformation Methods 0.000 description 2
- 230000004102 tricarboxylic acid cycle Effects 0.000 description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
- KJIOQYGWTQBHNH-UHFFFAOYSA-N undecanol Chemical compound CCCCCCCCCCCO KJIOQYGWTQBHNH-UHFFFAOYSA-N 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 230000005570 vertical transmission Effects 0.000 description 2
- 239000000341 volatile oil Substances 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- CPNQOBFWHSILHF-SPDVFEMOSA-N (2R,4R)-octane-2,4,7-triol Chemical compound OC(CC[C@H](C[C@@H](C)O)O)C CPNQOBFWHSILHF-SPDVFEMOSA-N 0.000 description 1
- LXJXRIRHZLFYRP-VKHMYHEASA-L (R)-2-Hydroxy-3-(phosphonooxy)-propanal Natural products O=C[C@H](O)COP([O-])([O-])=O LXJXRIRHZLFYRP-VKHMYHEASA-L 0.000 description 1
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 1
- XFRVVPUIAFSTFO-UHFFFAOYSA-N 1-Tridecanol Chemical compound CCCCCCCCCCCCCO XFRVVPUIAFSTFO-UHFFFAOYSA-N 0.000 description 1
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
- 108010060511 4-Aminobutyrate Transaminase Proteins 0.000 description 1
- 101710094518 4-aminobutyrate aminotransferase Proteins 0.000 description 1
- 102100035923 4-aminobutyrate aminotransferase, mitochondrial Human genes 0.000 description 1
- SJZRECIVHVDYJC-UHFFFAOYSA-N 4-hydroxybutyric acid Chemical compound OCCCC(O)=O SJZRECIVHVDYJC-UHFFFAOYSA-N 0.000 description 1
- MEANFMOQMXYMCT-OLZOCXBDSA-N 5,10-methenyltetrahydrofolic acid Chemical compound C([C@H]1CNC2=C([N+]1=C1)C(=O)N=C(N2)N)N1C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C([O-])=O)C=C1 MEANFMOQMXYMCT-OLZOCXBDSA-N 0.000 description 1
- MMTYWJNSFWVPPS-UHFFFAOYSA-N 5-hydroxy-2-oxopentanoic acid Chemical compound OCCCC(=O)C(O)=O MMTYWJNSFWVPPS-UHFFFAOYSA-N 0.000 description 1
- 102220496137 5-hydroxytryptamine receptor 3B_K72N_mutation Human genes 0.000 description 1
- 102000004146 ATP citrate synthases Human genes 0.000 description 1
- 108090000662 ATP citrate synthases Proteins 0.000 description 1
- 108010092060 Acetate kinase Proteins 0.000 description 1
- 102000008146 Acetate-CoA ligase Human genes 0.000 description 1
- 108010049926 Acetate-CoA ligase Proteins 0.000 description 1
- 241000589220 Acetobacter Species 0.000 description 1
- 241001468163 Acetobacterium woodii Species 0.000 description 1
- 241000204392 Acetonema longum Species 0.000 description 1
- 241001453369 Achromobacter denitrificans Species 0.000 description 1
- 101001058938 Acidaminococcus fermentans (strain ATCC 25085 / DSM 20731 / CCUG 9996 / CIP 106432 / VR4) Glutaconyl-CoA decarboxylase subunit beta Proteins 0.000 description 1
- 241000589291 Acinetobacter Species 0.000 description 1
- 241000588626 Acinetobacter baumannii Species 0.000 description 1
- 241001165345 Acinetobacter baylyi Species 0.000 description 1
- 241000588624 Acinetobacter calcoaceticus Species 0.000 description 1
- 108010009924 Aconitate hydratase Proteins 0.000 description 1
- 241000948980 Actinobacillus succinogenes Species 0.000 description 1
- 102000057234 Acyl transferases Human genes 0.000 description 1
- 108700016155 Acyl transferases Proteins 0.000 description 1
- 241000567139 Aeropyrum pernix Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 241000589155 Agrobacterium tumefaciens Species 0.000 description 1
- QGZKDVFQNNGYKY-OUBTZVSYSA-N Ammonia-15N Chemical compound [15NH3] QGZKDVFQNNGYKY-OUBTZVSYSA-N 0.000 description 1
- 102000004118 Ammonia-Lyases Human genes 0.000 description 1
- 108090000673 Ammonia-Lyases Proteins 0.000 description 1
- 241000722954 Anaerobiospirillum succiniciproducens Species 0.000 description 1
- 241001136167 Anaerotignum propionicum Species 0.000 description 1
- 241000428313 Anaerotruncus colihominis Species 0.000 description 1
- 108010006591 Apoenzymes Proteins 0.000 description 1
- 241000893512 Aquifex aeolicus Species 0.000 description 1
- 241000473391 Archosargus rhomboidalis Species 0.000 description 1
- 241000193409 Bacillus azotoformans Species 0.000 description 1
- 241000193755 Bacillus cereus Species 0.000 description 1
- 241000194107 Bacillus megaterium Species 0.000 description 1
- 241000194103 Bacillus pumilus Species 0.000 description 1
- 101000950981 Bacillus subtilis (strain 168) Catabolic NAD-specific glutamate dehydrogenase RocG Proteins 0.000 description 1
- 235000016068 Berberis vulgaris Nutrition 0.000 description 1
- 241000335053 Beta vulgaris Species 0.000 description 1
- 241000219310 Beta vulgaris subsp. vulgaris Species 0.000 description 1
- 241000123777 Blautia obeum Species 0.000 description 1
- 241000589174 Bradyrhizobium japonicum Species 0.000 description 1
- 241000193764 Brevibacillus brevis Species 0.000 description 1
- 241000244203 Caenorhabditis elegans Species 0.000 description 1
- 241001189169 Caldalkalibacillus thermarum Species 0.000 description 1
- 241000253373 Caldanaerobacter subterraneus subsp. tengcongensis Species 0.000 description 1
- 241000589875 Campylobacter jejuni Species 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 101710167800 Capsid assembly scaffolding protein Proteins 0.000 description 1
- 102000004031 Carboxy-Lyases Human genes 0.000 description 1
- 241000195597 Chlamydomonas reinhardtii Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 241000191382 Chlorobaculum tepidum Species 0.000 description 1
- 241000192731 Chloroflexus aurantiacus Species 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- 108010036824 Citrate (pro-3S)-lyase Proteins 0.000 description 1
- 241001494522 Citrobacter amalonaticus Species 0.000 description 1
- 241000588917 Citrobacter koseri Species 0.000 description 1
- 241000951471 Citrus junos Species 0.000 description 1
- 241001430149 Clostridiaceae Species 0.000 description 1
- 241001112695 Clostridiales Species 0.000 description 1
- 241000193163 Clostridioides difficile Species 0.000 description 1
- 241001468165 Clostridium aminobutyricum Species 0.000 description 1
- 241001611022 Clostridium carboxidivorans Species 0.000 description 1
- 241001509496 Clostridium celatum Species 0.000 description 1
- 241000193468 Clostridium perfringens Species 0.000 description 1
- 241000429427 Clostridium saccharobutylicum Species 0.000 description 1
- 241000186524 Clostridium subterminale Species 0.000 description 1
- 241000193449 Clostridium tetani Species 0.000 description 1
- 241000186520 Clostridium tetanomorphum Species 0.000 description 1
- 241000193452 Clostridium tyrobutyricum Species 0.000 description 1
- 102000005870 Coenzyme A Ligases Human genes 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 102100039868 Cytoplasmic aconitate hydratase Human genes 0.000 description 1
- LXJXRIRHZLFYRP-VKHMYHEASA-N D-glyceraldehyde 3-phosphate Chemical compound O=C[C@H](O)COP(O)(O)=O LXJXRIRHZLFYRP-VKHMYHEASA-N 0.000 description 1
- 102000007528 DNA Polymerase III Human genes 0.000 description 1
- 108010071146 DNA Polymerase III Proteins 0.000 description 1
- 238000000018 DNA microarray Methods 0.000 description 1
- 102220518102 DNA-directed RNA polymerases I and III subunit RPAC2_A73R_mutation Human genes 0.000 description 1
- 206010011878 Deafness Diseases 0.000 description 1
- 241001421462 Desulfatibacillum alkenivorans Species 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 241000168726 Dictyostelium discoideum Species 0.000 description 1
- 241001053771 Dictyostelium discoideum AX4 Species 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 208000037595 EN1-related dorsoventral syndrome Diseases 0.000 description 1
- WQXNXVUDBPYKBA-UHFFFAOYSA-N Ectoine Natural products CC1=NCCC(C(O)=O)N1 WQXNXVUDBPYKBA-UHFFFAOYSA-N 0.000 description 1
- 241000190844 Erythrobacter Species 0.000 description 1
- 101000637245 Escherichia coli (strain K12) Endonuclease V Proteins 0.000 description 1
- 241000711944 Eubacteriaceae bacterium Species 0.000 description 1
- 241000186394 Eubacterium Species 0.000 description 1
- 241000193456 Eubacterium barkeri Species 0.000 description 1
- 241000186398 Eubacterium limosum Species 0.000 description 1
- 241000393498 Eubacterium plexicaudatum Species 0.000 description 1
- 241000195619 Euglena gracilis Species 0.000 description 1
- 108091029865 Exogenous DNA Proteins 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 241001134569 Flavonifractor plautii Species 0.000 description 1
- 108090000698 Formate Dehydrogenases Proteins 0.000 description 1
- 108010080982 Formate-tetrahydrofolate ligase Proteins 0.000 description 1
- 108010036781 Fumarate Hydratase Proteins 0.000 description 1
- 102100036160 Fumarate hydratase, mitochondrial Human genes 0.000 description 1
- 241000605975 Fusobacterium varium Species 0.000 description 1
- 241000193385 Geobacillus stearothermophilus Species 0.000 description 1
- 241000388455 Gigasiphon Species 0.000 description 1
- 241000589232 Gluconobacter oxydans Species 0.000 description 1
- 102000016901 Glutamate dehydrogenase Human genes 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102220594412 HLA class I histocompatibility antigen, C alpha chain_A73E_mutation Human genes 0.000 description 1
- 241000606768 Haemophilus influenzae Species 0.000 description 1
- 241000158363 Halanaerobium saccharolyticum Species 0.000 description 1
- 241000204946 Halobacterium salinarum Species 0.000 description 1
- 241000204988 Haloferax mediterranei Species 0.000 description 1
- 108091027305 Heteroduplex Proteins 0.000 description 1
- 108090001042 Hydro-Lyases Proteins 0.000 description 1
- 102000004867 Hydro-Lyases Human genes 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 241000605325 Hydrogenobacter thermophilus Species 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 241000411974 Ilyobacter polytropus Species 0.000 description 1
- 108010081409 Iron-Sulfur Proteins Proteins 0.000 description 1
- 102000005298 Iron-Sulfur Proteins Human genes 0.000 description 1
- 102000012011 Isocitrate Dehydrogenase Human genes 0.000 description 1
- 108010075869 Isocitrate Dehydrogenase Proteins 0.000 description 1
- 102000004195 Isomerases Human genes 0.000 description 1
- 108090000769 Isomerases Proteins 0.000 description 1
- 241000588915 Klebsiella aerogenes Species 0.000 description 1
- 201000008225 Klebsiella pneumonia Diseases 0.000 description 1
- 235000014663 Kluyveromyces fragilis Nutrition 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- HXEACLLIILLPRG-YFKPBYRVSA-N L-pipecolic acid Chemical compound [O-]C(=O)[C@@H]1CCCC[NH2+]1 HXEACLLIILLPRG-YFKPBYRVSA-N 0.000 description 1
- 241000933069 Lachnoclostridium phytofermentans Species 0.000 description 1
- 241000904817 Lachnospiraceae bacterium Species 0.000 description 1
- 241001112724 Lactobacillales Species 0.000 description 1
- 240000001929 Lactobacillus brevis Species 0.000 description 1
- 235000013957 Lactobacillus brevis Nutrition 0.000 description 1
- 102100025357 Lipid-phosphate phosphatase Human genes 0.000 description 1
- 108010011449 Long-chain-fatty-acid-CoA ligase Proteins 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 108010026217 Malate Dehydrogenase Proteins 0.000 description 1
- 102000013460 Malate Dehydrogenase Human genes 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000589195 Mesorhizobium loti Species 0.000 description 1
- 241001302042 Methanothermobacter thermautotrophicus Species 0.000 description 1
- 108010010685 Methenyltetrahydrofolate cyclohydrolase Proteins 0.000 description 1
- 102000005954 Methylenetetrahydrofolate Reductase (NADPH2) Human genes 0.000 description 1
- 108010030837 Methylenetetrahydrofolate Reductase (NADPH2) Proteins 0.000 description 1
- 102220482769 Mitochondrial coenzyme A diphosphatase NUDT8_K65A_mutation Human genes 0.000 description 1
- 241000193459 Moorella thermoacetica Species 0.000 description 1
- 241000235388 Mucorales Species 0.000 description 1
- 206010028289 Muscle atrophy Diseases 0.000 description 1
- 208000029578 Muscle disease Diseases 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 241000186359 Mycobacterium Species 0.000 description 1
- 241000186367 Mycobacterium avium Species 0.000 description 1
- 241000187492 Mycobacterium marinum Species 0.000 description 1
- 241001607431 Mycobacterium marinum M Species 0.000 description 1
- 241000187480 Mycobacterium smegmatis Species 0.000 description 1
- 241001025881 Mycobacterium smegmatis str. MC2 155 Species 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 241000863422 Myxococcus xanthus Species 0.000 description 1
- 241000167284 Natranaerobius Species 0.000 description 1
- 241001495644 Nicotiana glutinosa Species 0.000 description 1
- 241001503673 Nocardia farcinica Species 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000193390 Parageobacillus thermoglucosidasius Species 0.000 description 1
- 241001459585 Pelosinus fermentans Species 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 108700023175 Phosphate acetyltransferases Proteins 0.000 description 1
- OAICVXFJPJFONN-OUBTZVSYSA-N Phosphorus-32 Chemical compound [32P] OAICVXFJPJFONN-OUBTZVSYSA-N 0.000 description 1
- OAICVXFJPJFONN-NJFSPNSNSA-N Phosphorus-33 Chemical compound [33P] OAICVXFJPJFONN-NJFSPNSNSA-N 0.000 description 1
- 102000013566 Plasminogen Human genes 0.000 description 1
- 108010051456 Plasminogen Proteins 0.000 description 1
- 102000001938 Plasminogen Activators Human genes 0.000 description 1
- 108010001014 Plasminogen Activators Proteins 0.000 description 1
- 206010035717 Pneumonia klebsiella Diseases 0.000 description 1
- 229920000331 Polyhydroxybutyrate Polymers 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 101710130420 Probable capsid assembly scaffolding protein Proteins 0.000 description 1
- 102220636347 Proline-rich protein 27_I44L_mutation Human genes 0.000 description 1
- 102000055027 Protein Methyltransferases Human genes 0.000 description 1
- 108700040121 Protein Methyltransferases Proteins 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 241001528479 Pseudoflavonifractor capillosus Species 0.000 description 1
- 241000947836 Pseudomonadaceae Species 0.000 description 1
- 241001248479 Pseudomonadales Species 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 241000186336 Pseudopropionibacterium propionicum Species 0.000 description 1
- 101710182361 Pyruvate:ferredoxin oxidoreductase Proteins 0.000 description 1
- 108010047066 R 396 Proteins 0.000 description 1
- 241001148115 Rhizobium etli Species 0.000 description 1
- 241000235527 Rhizopus Species 0.000 description 1
- 240000005384 Rhizopus oryzae Species 0.000 description 1
- 235000013752 Rhizopus oryzae Nutrition 0.000 description 1
- 241000191025 Rhodobacter Species 0.000 description 1
- 241000191043 Rhodobacter sphaeroides Species 0.000 description 1
- 241000190984 Rhodospirillum rubrum Species 0.000 description 1
- 241001394655 Roseburia inulinivorans Species 0.000 description 1
- 241000516658 Roseiflexus castenholzii Species 0.000 description 1
- DFPOZTRSOAQFIK-UHFFFAOYSA-N S,S-dimethyl-beta-propiothetin Chemical compound C[S+](C)CCC([O-])=O DFPOZTRSOAQFIK-UHFFFAOYSA-N 0.000 description 1
- FQFRDDVZPBFYST-CITAKDKDSA-N S-[2-[3-[[(2R)-4-[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-2-hydroxy-3,3-dimethylbutanoyl]amino]propanoylamino]ethyl] 4-hydroxybut-2-enethioate Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C=CCO)O[C@H]1N1C2=NC=NC(N)=C2N=C1 FQFRDDVZPBFYST-CITAKDKDSA-N 0.000 description 1
- 244000253911 Saccharomyces fragilis Species 0.000 description 1
- 235000018368 Saccharomyces fragilis Nutrition 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 101710204410 Scaffold protein Proteins 0.000 description 1
- 241000605031 Selenomonas ruminantium Species 0.000 description 1
- 241000607715 Serratia marcescens Species 0.000 description 1
- 241000763410 Shuttleworthia satelles Species 0.000 description 1
- 244000044822 Simmondsia californica Species 0.000 description 1
- 235000004433 Simmondsia californica Nutrition 0.000 description 1
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 1
- 208000010040 Sprains and Strains Diseases 0.000 description 1
- 241000194020 Streptococcus thermophilus Species 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 241000187432 Streptomyces coelicolor Species 0.000 description 1
- 241000187392 Streptomyces griseus Species 0.000 description 1
- 102000019259 Succinate Dehydrogenase Human genes 0.000 description 1
- 108010012901 Succinate Dehydrogenase Proteins 0.000 description 1
- 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 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 235000021536 Sugar beet Nutrition 0.000 description 1
- 241000205101 Sulfolobus Species 0.000 description 1
- 241000205091 Sulfolobus solfataricus Species 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-NJFSPNSNSA-N Sulfur-34 Chemical compound [34S] NINIDFKCEFEMDL-NJFSPNSNSA-N 0.000 description 1
- NINIDFKCEFEMDL-AKLPVKDBSA-N Sulfur-35 Chemical compound [35S] NINIDFKCEFEMDL-AKLPVKDBSA-N 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 241001657755 Thermincola potens Species 0.000 description 1
- 241001147775 Thermoanaerobacter brockii Species 0.000 description 1
- 241000186337 Thermoanaerobacter ethanolicus Species 0.000 description 1
- 241001137871 Thermoanaerobacterium saccharolyticum Species 0.000 description 1
- 241000193446 Thermoanaerobacterium thermosaccharolyticum Species 0.000 description 1
- 241001147773 Thermoanaerobacterium xylanolyticum Species 0.000 description 1
- 241001133197 Thermosediminibacter oceani Species 0.000 description 1
- 241000204666 Thermotoga maritima Species 0.000 description 1
- 102000002932 Thiolase Human genes 0.000 description 1
- 108060008225 Thiolase Proteins 0.000 description 1
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 241000589892 Treponema denticola Species 0.000 description 1
- 241001136486 Trichocomaceae Species 0.000 description 1
- 241000224527 Trichomonas vaginalis Species 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 241000204063 Tsukamurella paurometabola Species 0.000 description 1
- 241001034637 Tsukamurella paurometabola DSM 20162 Species 0.000 description 1
- 241000607598 Vibrio Species 0.000 description 1
- 241000607626 Vibrio cholerae Species 0.000 description 1
- 241000607272 Vibrio parahaemolyticus Species 0.000 description 1
- 241000607265 Vibrio vulnificus Species 0.000 description 1
- 241000235013 Yarrowia Species 0.000 description 1
- 241000235015 Yarrowia lipolytica Species 0.000 description 1
- 241000589153 Zoogloea ramigera Species 0.000 description 1
- 241000588901 Zymomonas Species 0.000 description 1
- 241000342876 [Clostridium] asparagiforme Species 0.000 description 1
- 241001246487 [Clostridium] bolteae Species 0.000 description 1
- 241000186561 [Clostridium] clostridioforme Species 0.000 description 1
- 241001656805 [Clostridium] methylpentosum Species 0.000 description 1
- 241001656794 [Clostridium] saccharolyticum Species 0.000 description 1
- 241001531197 [Eubacterium] hallii Species 0.000 description 1
- 241000029538 [Mannheimia] succiniciproducens Species 0.000 description 1
- 241001464867 [Ruminococcus] gnavus Species 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000000789 acetogenic effect Effects 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 238000005377 adsorption chromatography Methods 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000004191 allura red AC Substances 0.000 description 1
- 150000004716 alpha keto acids Chemical class 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 238000010640 amide synthesis reaction Methods 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000009604 anaerobic growth Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 238000010364 biochemical engineering Methods 0.000 description 1
- 238000005842 biochemical reaction Methods 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- CLQZEZFINZCXFG-UHFFFAOYSA-N butane-1,1,4-triol Chemical compound OCCCC(O)O CLQZEZFINZCXFG-UHFFFAOYSA-N 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000003575 carbonaceous material Substances 0.000 description 1
- JJWKPURADFRFRB-UHFFFAOYSA-N carbonyl sulfide Chemical compound O=C=S JJWKPURADFRFRB-UHFFFAOYSA-N 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 210000004671 cell-free system Anatomy 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 210000002230 centromere Anatomy 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 238000012412 chemical coupling Methods 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- VEXZGXHMUGYJMC-OUBTZVSYSA-N chlorane Chemical compound [36ClH] VEXZGXHMUGYJMC-OUBTZVSYSA-N 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- VEXZGXHMUGYJMC-IGMARMGPSA-N chlorine-35 Chemical compound [35ClH] VEXZGXHMUGYJMC-IGMARMGPSA-N 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 238000003501 co-culture Methods 0.000 description 1
- 230000003931 cognitive performance Effects 0.000 description 1
- 230000001447 compensatory effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000005094 computer simulation Methods 0.000 description 1
- 238000001944 continuous distillation Methods 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- KFWWCMJSYSSPSK-PAXLJYGASA-N crotonoyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)/C=C/C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 KFWWCMJSYSSPSK-PAXLJYGASA-N 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000030609 dephosphorylation Effects 0.000 description 1
- 238000006209 dephosphorylation reaction Methods 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 229940111685 dibasic potassium phosphate Drugs 0.000 description 1
- 229910001882 dioxygen Inorganic materials 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- BIQSIHSUENWJGR-LHWPGRLPSA-L disodium;(2s)-2-aminopentanedioate;hydrate Chemical compound O.[Na+].[Na+].[O-]C(=O)[C@@H](N)CCC([O-])=O BIQSIHSUENWJGR-LHWPGRLPSA-L 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- NOPFSRXAKWQILS-UHFFFAOYSA-N docosan-1-ol Chemical class CCCCCCCCCCCCCCCCCCCCCCO NOPFSRXAKWQILS-UHFFFAOYSA-N 0.000 description 1
- LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 1
- 238000005553 drilling Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- WQXNXVUDBPYKBA-YFKPBYRVSA-N ectoine Chemical compound CC1=[NH+][C@H](C([O-])=O)CCN1 WQXNXVUDBPYKBA-YFKPBYRVSA-N 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000000909 electrodialysis Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 229940092559 enterobacter aerogenes Drugs 0.000 description 1
- 150000002118 epoxides Chemical class 0.000 description 1
- 235000020774 essential nutrients Nutrition 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000004136 fatty acid synthesis Effects 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000005189 flocculation Methods 0.000 description 1
- 230000016615 flocculation Effects 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- 238000012246 gene addition Methods 0.000 description 1
- 238000003209 gene knockout Methods 0.000 description 1
- 230000004110 gluconeogenesis Effects 0.000 description 1
- 230000004190 glucose uptake Effects 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 229940047650 haemophilus influenzae Drugs 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- FIPPFBHCBUDBRR-UHFFFAOYSA-N henicosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCO FIPPFBHCBUDBRR-UHFFFAOYSA-N 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000012188 high-throughput screening assay Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 238000000126 in silico method Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 229940031154 kluyveromyces marxianus Drugs 0.000 description 1
- HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 description 1
- 229920005610 lignin Polymers 0.000 description 1
- 238000009630 liquid culture Methods 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000005374 membrane filtration Methods 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 238000012269 metabolic engineering Methods 0.000 description 1
- 230000033607 mismatch repair Effects 0.000 description 1
- 230000004065 mitochondrial dysfunction Effects 0.000 description 1
- 235000013379 molasses Nutrition 0.000 description 1
- 229940111688 monobasic potassium phosphate Drugs 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 201000000585 muscular atrophy Diseases 0.000 description 1
- 230000000869 mutational effect Effects 0.000 description 1
- 229940043348 myristyl alcohol Drugs 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000003345 natural gas Substances 0.000 description 1
- 239000006225 natural substrate Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 235000006286 nutrient intake Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000000065 osmolyte Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- QVGXLLKOCUKJST-OUBTZVSYSA-N oxygen-17 atom Chemical compound [17O] QVGXLLKOCUKJST-OUBTZVSYSA-N 0.000 description 1
- QVGXLLKOCUKJST-NJFSPNSNSA-N oxygen-18 atom Chemical compound [18O] QVGXLLKOCUKJST-NJFSPNSNSA-N 0.000 description 1
- 238000005373 pervaporation Methods 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 229930029653 phosphoenolpyruvate Natural products 0.000 description 1
- DTBNBXWJWCWCIK-UHFFFAOYSA-N phosphoenolpyruvic acid Chemical compound OC(=O)C(=C)OP(O)(O)=O DTBNBXWJWCWCIK-UHFFFAOYSA-N 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229940097886 phosphorus 32 Drugs 0.000 description 1
- 230000036314 physical performance Effects 0.000 description 1
- 229940127126 plasminogen activator Drugs 0.000 description 1
- 239000005015 poly(hydroxybutyrate) Substances 0.000 description 1
- 229920001748 polybutylene Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 108020001775 protein parts Proteins 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000033458 reproduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 238000001223 reverse osmosis Methods 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 102220195737 rs1057518115 Human genes 0.000 description 1
- 102220232983 rs143630318 Human genes 0.000 description 1
- 102220265966 rs146527410 Human genes 0.000 description 1
- 102220332475 rs1554776686 Human genes 0.000 description 1
- 102220164107 rs201867379 Human genes 0.000 description 1
- 102220321773 rs756787732 Human genes 0.000 description 1
- WJQCDDRZANTJDH-CITAKDKDSA-N s-[2-[3-[[(2r)-4-[[[(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-2-hydroxy-3,3-dimethylbutanoyl]amino]propanoylamino]ethyl] 4-oxobutanethioate Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CCC=O)O[C@H]1N1C2=NC=NC(N)=C2N=C1 WJQCDDRZANTJDH-CITAKDKDSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- NINIDFKCEFEMDL-IGMARMGPSA-N sulfur-32 atom Chemical compound [32S] NINIDFKCEFEMDL-IGMARMGPSA-N 0.000 description 1
- NINIDFKCEFEMDL-OUBTZVSYSA-N sulfur-33 atom Chemical compound [33S] NINIDFKCEFEMDL-OUBTZVSYSA-N 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 102000055501 telomere Human genes 0.000 description 1
- 108091035539 telomere Proteins 0.000 description 1
- 210000003411 telomere Anatomy 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 229960000187 tissue plasminogen activator Drugs 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 229940087291 tridecyl alcohol Drugs 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 229940057402 undecyl alcohol Drugs 0.000 description 1
- UATIGEHITDTAGF-CITAKDKDSA-N vinylacetyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CC=C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 UATIGEHITDTAGF-CITAKDKDSA-N 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 238000012070 whole genome sequencing analysis Methods 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/0004—Oxidoreductases (1.)
- C12N9/0008—Oxidoreductases (1.) acting on the aldehyde or oxo group of donors (1.2)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P7/00—Preparation of oxygen-containing organic compounds
- C12P7/02—Preparation of oxygen-containing organic compounds containing a hydroxy group
- C12P7/04—Preparation of oxygen-containing organic compounds containing a hydroxy group acyclic
- C12P7/18—Preparation of oxygen-containing organic compounds containing a hydroxy group acyclic polyhydric
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P7/00—Preparation of oxygen-containing organic compounds
- C12P7/24—Preparation of oxygen-containing organic compounds containing a carbonyl group
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y102/00—Oxidoreductases acting on the aldehyde or oxo group of donors (1.2)
- C12Y102/01—Oxidoreductases acting on the aldehyde or oxo group of donors (1.2) with NAD+ or NADP+ as acceptor (1.2.1)
- C12Y102/01003—Aldehyde dehydrogenase (NAD+) (1.2.1.3)
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Cosmetics (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Enzymes And Modification Thereof (AREA)
- Compositions Of Macromolecular Compounds (AREA)
Abstract
Description
本発明の実施形態において、例えば以下の項目が提供される。
(項目1)
(a)配列番号1、2もしくは3としてまたは表4で参照されるアミノ酸配列をコードする核酸分子であって、前記アミノ酸配列が、表1、2および/または3で示されるアミノ酸置換のうちの1つまたは複数を含む、核酸分子;
(b)高度にストリンジェントなハイブリダイゼーション条件下で(a)の前記核酸にハイブリダイズし、表1、2および/または3で示されるアミノ酸置換のうちの1つまたは複数をコードする核酸配列を含む核酸分子;
(c)ループA(配列番号5)および/またはループB(配列番号6)のコンセンサス配列を含むアミノ酸配列をコードする核酸分子であって、前記アミノ酸配列が、表1、2および/または3で示されるアミノ酸置換のうちの1つまたは複数を含む、核酸分子;ならびに
(d)(a)または(b)に相補的な核酸分子
から選択される単離された核酸分子。
(項目2)
前記1つまたは複数のアミノ酸置換以外の前記アミノ酸配列が、配列番号1、2もしくは3でまたは表4で参照されるアミノ酸配列と少なくとも65%、70%、75%、80%、85%、90%、95%、98%もしくは99%の配列同一性を有するか、またはこれと同一である、項目1に記載の単離された核酸分子。
(項目3)
前記アミノ酸配列が、表1、2および/または3で示されるアミノ酸置換のうちの少なくとも2、3、4、5、6、7、8、9、10、11、12、13、14、15または16個を含む、項目1または2に記載の核酸。
(項目4)
項目1から3のいずれか一項に記載の核酸分子を含有するベクター。
(項目5)
発現ベクターである、項目4に記載のベクター。
(項目6)
二本鎖DNAを含む、項目4または5に記載のベクター。
(項目7)
配列番号1、2もしくは3としてまたは表4で参照されるアミノ酸配列を含む単離されたポリペプチドであって、前記アミノ酸配列が、表1、2および/または3で示されるアミノ酸置換のうちの1つまたは複数を含む、単離されたポリペプチド。
(項目8)
ループA(配列番号5)および/またはループB(配列番号6)のコンセンサスアミノ酸配列を含む単離されたポリペプチド。
(項目9)
配列番号1、2もしくは3としてまたは表4で参照されるアミノ酸配列を含む単離されたポリペプチドであって、前記アミノ酸配列が、表1、2および/または3で示されるアミノ酸置換のうちの1つまたは複数を含み、前記1つまたは複数のアミノ酸置換以外の前記アミノ酸配列が、配列番号1、2もしくは3としてまたは表4で参照されるアミノ酸配列と少なくとも65%、70%、75%、80%、85%、90%、95%、98%もしくは99%の配列同一性を有するか、またはこれと同一である、単離されたポリペプチド。
(項目10)
前記アミノ酸配列が、1~100個のアミノ酸位置における保存的アミノ酸置換をさらに含み、前記位置が、表1、2および/または3で示される前記1つまたは複数のアミノ酸置換以外である、項目9に記載の単離されたポリペプチド。
(項目11)
前記アミノ酸配列が、表1、2および/または3で示される前記1つまたは複数のアミノ酸置換以外に、親配列と比較して2~300個のアミノ酸位置で改変を含まず、前記位置が、配列番号1、2もしくは3としてまたは表4で参照される前記アミノ酸配列のうちの2、3、4または5つと同一である位置から選択される、項目7から10のいずれか一項に記載の単離されたポリペプチド。
(項目12)
前記アミノ酸配列が、表1、2および/または3で示されるアミノ酸置換のうちの少なくとも2、3、4、5、6、7、8、9、10、11、12、13、14、15または16個を含む、項目7から11のいずれか一項に記載の単離されたポリペプチド。
(項目13)
アルデヒドデヒドロゲナーゼをコードする、項目7から12のいずれか一項に記載の単離されたポリペプチド。
(項目14)
3-ヒドロキシブチリルCoAを3-ヒドロキシブチルアルデヒドに転換し得る、項目7から13のいずれか一項に記載の単離されたポリペプチド。
(項目15)
4-ヒドロキシブチリルCoAを4-ヒドロキシブチルアルデヒドに転換し得る、項目7から13のいずれか一項に記載の単離されたポリペプチド。
(項目16)
親ポリペプチドと比べてより高い活性を有する、項目7から15のいずれか一項に記載の単離されたポリペプチド。
(項目17)
3-ヒドロキシ-(S)-ブチリルCoAよりも3-ヒドロキシ-(R)-ブチリルCoAについてより高い活性を有する、項目7から14のいずれか一項に記載の単離されたポリペプチド。
(項目18)
アセチルCoAよりも3-ヒドロキシブチリルCoAについてより高い特異性を有する、項目7から14のいずれか一項に記載の単離されたポリペプチド。
(項目19)
アセチルCoAよりも4-ヒドロキシブチリルCoAについてより高い特異性を有する、項目7から13または15のいずれか一項に記載の単離されたポリペプチド。
(項目20)
細胞または細胞抽出物における副産物の生成を低減する、項目7から15のいずれか一項に記載の単離されたポリペプチド。
(項目21)
前記副産物が、エタノールまたは4-ヒドロキシ-2-ブタノンである、項目20に記載の単離されたポリペプチド。
(項目22)
親ポリペプチドと比べてより高いkcatを有する、項目7から15のいずれか一項に記載の単離されたポリペプチド。
(項目23)
項目4から6のいずれか一項に記載のベクターを含む細胞。
(項目24)
項目1から3のいずれか一項に記載の核酸を含む細胞。
(項目25)
前記核酸分子が、前記細胞の染色体に組み込まれている、項目24に記載の細胞。
(項目26)
前記組込みが、部位特異的である、項目25に記載の細胞。
(項目27)
前記核酸分子が発現される、項目23から26のいずれか一項に記載の細胞。
(項目28)
項目7から22のいずれか一項に記載のポリペプチドを含む細胞。
(項目29)
微生物体である、項目23から28のいずれか一項に記載の細胞。
(項目30)
前記微生物体が、細菌、酵母または真菌である、項目29に記載の細胞。
(項目31)
単離された真核細胞である、項目23から28のいずれか一項に記載の細胞。
(項目32)
3-ヒドロキシブチルアルデヒド(3-HBal)および/もしくは1,3-ブタンジオール(1,3-BDO)またはそのエステルもしくはアミドを生成する経路を含む、項目23から31のいずれか一項に記載の細胞。
(項目33)
4-ヒドロキシブチルアルデヒド(4-HBal)および/もしくは1,4-ブタンジオール(1,4-BDO)またはそのエステルもしくはアミドを生成する経路を含む、項目23から31のいずれか一項に記載の細胞。
(項目34)
発酵することができる、項目23から33のいずれか一項に記載の細胞。
(項目35)
前記ポリペプチドについての少なくとも1つの基質をさらに含む、項目23から34のいずれか一項に記載の細胞。
(項目36)
前記基質が、3-ヒドロキシブチリルCoAである、項目35に記載の細胞。
(項目37)
前記基質が、3-ヒドロキシ-(R)-ブチリルCoAである、項目36に記載の細胞。
(項目38)
3-ヒドロキシ-(S)-ブチリルCoAよりも3-ヒドロキシ-(R)-ブチリルCoAについてより高い活性を有する、項目36または37に記載の細胞。
(項目39)
前記基質が、4-ヒドロキシブチリルCoAである、項目35に記載の細胞。
(項目40)
生物触媒としての、項目7から22のいずれか一項に記載のポリペプチドの使用。
(項目41)
項目7から22のいずれか一項に記載のポリペプチドおよび前記ポリペプチドについての少なくとも1つの基質を含む組成物。
(項目42)
前記ポリペプチドが、in vitro条件下で前記基質と反応することができる、項目41に記載の組成物。
(項目43)
前記基質が、3-ヒドロキシブチリルCoAである、項目41または42に記載の組成物。
(項目44)
前記基質が、3-ヒドロキシ-(R)-ブチリルCoAである、項目43に記載の組成物。
(項目45)
前記基質が、4-ヒドロキシブチリルCoAである、項目41または42に記載の組成物。
(項目46)
項目23から39のいずれか一項に記載の細胞を含む培地。
(項目47)
項目4から6のいずれか一項に記載のベクターを、発酵することができる細胞に導入する工程を含む、宿主株を構築する方法。
(項目48)
3-ヒドロキシブチルアルデヒド(3-HBal)および/もしくは1,3-ブタンジオール(1,3-BDO)またはそのエステルもしくはアミドを生成するための方法であって、項目23から39のいずれか一項に記載の細胞を培養して、3-HBalおよび/もしくは1,3-BDOまたはそのエステルもしくはアミドを生成する工程を含む方法。
(項目49)
4-ヒドロキシブチルアルデヒド(4-HBal)および/もしくは1,4-ブタンジオール(1,4-BDO)またはそのエステルもしくはアミドを生成するための方法であって、項目23から39のいずれか一項に記載の細胞を培養して、4-HBalおよび/もしくは1,4-BDOまたはそのエステルもしくはアミドを生成する工程を含む方法。
(項目50)
前記細胞が、実質的に嫌気性の培地中にある、項目48または49に記載の方法。
(項目51)
前記3-HBalおよび/もしくは1,3-BDOもしくは前記4-HBalおよび/もしくは1,4-BDO、またはそのエステルもしくはアミドを単離または精製する工程をさらに含む、項目48から50のいずれか一項に記載の方法。
(項目52)
前記単離または精製する工程が、蒸留を含む、項目51に記載の方法。
(項目53)
生物由来3-HBalおよび/もしくは1,3-BDOまたは4-HBalおよび/もしくは1,4-BDOを含む培地であって、前記生物由来3-HBalおよび/もしくは1,3-BDOまたは4-HBalおよび/もしくは1,4-BDOが、大気二酸化炭素取り込み供給源を反映する炭素-12、炭素-13および炭素-14の同位体比を有し、前記生物由来3-HBalおよび/もしくは1,3-BDOまたは4-HBalおよび/もしくは1,4-BDOが、項目23から39のいずれか一項に記載の細胞または項目48から52のいずれか一項に記載の方法によって生成される、培地。
(項目54)
前記細胞から分離されている、項目53に記載の培地。
(項目55)
大気二酸化炭素取り込み供給源を反映する炭素-12、炭素-13および炭素-14の同位体比を有する、3-ヒドロキシブチルアルデヒド(3-HBal)および/もしくは1,3-ブタンジオール(1,3-BDO)または4-ヒドロキシブチルアルデヒド(4-HBal)および/もしくは1,4-ブタンジオール(1,4-BDO)であって、項目23から39のいずれか一項に記載の細胞または項目48から52のいずれか一項に記載の方法によって生成される、3-HBalおよび/もしくは1,3-BDOまたは4-HBalおよび/もしくは1,4-BDO。
(項目56)
少なくとも80%、少なくとも85%、少なくとも90%、少なくとも95%または少なくとも98%のFm値を有する、項目55に記載の3-HBalおよび/もしくは1,3-BDOまたは4-HBalおよび/もしくは1,4-BDO。
(項目57)
項目23から39のいずれか一項に記載の細胞または項目48から52のいずれか一項に記載の方法によって生成された3-ヒドロキシブチルアルデヒド(3-HBal)および/もしくは1,3-ブタンジオール(1,3-BDO)または4-ヒドロキシブチルアルデヒド(4-HBal)および/もしくは1,4-ブタンジオール(1,4-BDO)。
(項目58)
大気二酸化炭素取り込み供給源を反映する炭素-12、炭素-13および炭素-14の同位体比を有する3-ヒドロキシブチルアルデヒド(3-HBal)および/または1,3-ブタンジオール(1,3-BDO)であって、項目23から39のいずれか一項に記載の細胞または項目48から52のいずれか一項に記載の方法によって生成され、R形態のエナンチオマーが富化されている3-HBalおよび/または1,3-BDO。
(項目59)
少なくとも80%、少なくとも85%、少なくとも90%、少なくとも95%または少なくとも98%のFm値を有する、項目58に記載の3-HBalおよび/または1,3-BDO。
(項目60)
項目23から39のいずれか一項に記載の細胞または項目48から52のいずれか一項に記載の方法によって生成された3-ヒドロキシブチルアルデヒド(3-HBal)および/または1,3-ブタンジオール(1,3-BDO)であって、R形態のエナンチオマーが富化されている3-HBalおよび/または1,3-BDO。
(項目61)
前記R形態が、前記3-HBalおよび/または1,3-BDOの95%、96%、97%、98%、99%、99.5%または99.9%を超える、項目60に記載の3-HBalおよび/または1,3-BDO。
(項目62)
項目58から61のいずれか一項に記載の3-HBalおよび/もしくは1,3-BDOまたは4-HBalおよび/もしくは1,4-BDO、ならびにそれぞれ、前記3-HBalおよび/もしくは1,3-BDOまたは4-HBalもしくは1,4-BDO以外の化合物を含む組成物。
(項目63)
前記3-HBalおよび/もしくは1,3-BDOまたは前記4-HBalおよび/もしくは1,4-BDO以外の前記化合物が、それぞれ、前記3-HBalおよび/もしくは1,3-BDOもしくは前記4-HBalおよび/もしくは1,4-BDOを生成するか、または項目7から22のいずれか一項に記載のポリペプチドを発現する細胞の部分である、項目62に記載の組成物。
(項目64)
項目55から61のいずれか一項に記載の3-HBalおよび/もしくは1,3-BDOもしくは4-HBalおよび/もしくは1,4-BDO、または前記3-HBalおよび/もしくは1,3-BDOもしくは前記4-HBalおよび/もしくは1,4-BDOを生成する細胞の細胞溶解物もしくは培養上清を含む組成物。
(項目65)
項目55から61のいずれか一項に記載の3-HBalおよび/もしくは1,3-BDOまたは4-HBalおよび/もしくは1,4-BDOを含む製品であって、プラスチック、弾性繊維、ポリウレタン、ポリエステル、ポリヒドロキシアルカノエート、ポリ-4-ヒドロキシブチレート(P4HB)またはそのコポリマー、ポリ(テトラメチレンエーテル)グリコール(PTMEG)、ポリブチレンテレフタレート(PBT)、ポリウレタン-ポリ尿素コポリマー、ナイロン、有機溶媒、ポリウレタン樹脂、ポリエステル樹脂、血糖低下剤、ブタジエンまたはブタジエンベースの製品である製品。
(項目66)
化粧品または食品添加物である、項目65に記載の製品。
(項目67)
少なくとも5%、少なくとも10%、少なくとも20%、少なくとも30%、少なくとも40%または少なくとも50%の生物由来3-HBalおよび/もしくは1,3-BDOまたは生物由来4-HBalおよび/もしくは1,4-BDOを含む、項目65または66に記載の製品。
(項目68)
繰返し単位として、生成された3-HBalおよび/もしくは1,3-BDOまたは生成された4-HBalおよび/もしくは1,4-BDOの部分を含む、項目65から67のいずれか一項に記載の製品。
(項目69)
項目65、67または68のいずれか一項に記載の製品を成型することによって得られた成型製品。
(項目70)
項目65から68のいずれか一項に記載の製品を生成するためのプロセスであって、前記製品を生成する反応において、前記3-HBalおよび/もしくは1,3-BDOまたは前記4-HBalおよび/もしくは1,4-BDOを、それ自体または別の化合物と化学反応させる工程を含むプロセス。
(項目71)
項目69に記載の製品を生成するためのプロセスであって、前記製品を生成する反応において、前記3-HBalおよび/もしくは1,3-BDOまたは前記4-HBalおよび/もしくは1,4-BDOを、それ自体または別の化合物と化学反応させる工程を含むプロセス。
(項目72)
3-ヒドロキシブチルアルデヒド(3-HBal)および/もしくは1,3-ブタンジオール(1,3-BDO)またはそのエステルもしくはアミドを生成するための方法であって、基質を項目7から22のいずれか一項に記載のポリペプチドに提供する工程と、前記基質を3-HBalおよび/または1,3-BDOに転換する工程とを含み、前記基質が、1,3-ヒドロキシブチリルCoAのラセミ混合物である、方法。
(項目73)
前記3-HBalおよび/または1,3-BDOは、R形態のエナンチオマー的が富化されている、項目72に記載の方法。
(項目74)
4-ヒドロキシブチルアルデヒド(4-HBal)および/もしくは1,4-ブタンジオール(1,4-BDO)またはそのエステルもしくはアミドを生成するための方法であって、基質を項目7から22のいずれか一項に記載のポリペプチドに提供する工程と、前記基質を4-HBalおよび/または1,4-BDOに転換する工程とを含み、前記基質が、1,4-ヒドロキシブチリルCoAである、方法。
(項目75)
前記ポリペプチドが、細胞中、細胞溶解物中に存在するか、または細胞もしくは細胞溶解物から単離される、項目72から74のいずれか一項に記載の方法。
(項目76)
3-HBalおよび/もしくは1,3-BDOまたは4-HBalおよび/もしくは1,4-BDOを生成するための方法であって、項目23から39のいずれか一項に記載の細胞の溶解物をインキュベートして、3-HBalおよび/もしくは1,3-BDOまたは4-HBalおよび/もしくは1,4-BDOを生成する工程を含む方法。
(項目77)
前記細胞溶解物が、第2の細胞溶解物と混合され、前記第2の細胞溶解物が、項目7から22のいずれか一項に記載のポリペプチドの基質、または3-HBalおよび/もしくは1,3-BDOもしくは4-HBalおよび/もしくは1,4-BDOの下流生成物を生成する酵素活性を含む、項目76に記載の方法。
(項目78)
項目7から22のいずれか一項に記載のポリペプチドを生成するための方法であって、細胞において前記ポリペプチドを発現する工程を含む方法。
(項目79)
項目7から22のいずれか一項に記載のポリペプチドを生成するための方法であって、項目1から3のいずれか一項に記載の核酸または項目4から6に記載のベクターをin vitroで転写および翻訳して、前記ポリペプチドを生成する工程を含む方法。
sidansが挙げられるが、これに限定されない)、Bacillus azotoformans、Thermincola potens、Fusobacterium種(例えば、but not limited to Fusobacterium nucleatum、Fusobacterium ulceransが挙げられるが、これらに限定されない)、Fusobacterium varium、Ruminococcus種(例えば、Ruminococcus gnavus、Ruminococcus obeum)、Lachnospiraceae bacterium、Flavonifractor plautii、Roseburia inulinivorans、Acetobacterium woodii、Eubacterium種(例えば、Eubacterium plexicaudatum、Eubacterium hallii、Eubacterium limosum、Eubacterium yuriiが挙げられるが、これらに限定されない)、Eubacteriaceae bacterium、Thermosediminibacter oceani、Ilyobacter polytropus、Shuttleworthia satelles、Halanaerobium saccharolyticum、Thermoanaerobacter ethanolicus、Rhodospirillum rubrum、Vibrio、Propionibacterium propionicum、および本明細書に開示されるかまたは表4に記載のアルデヒドデヒドロゲナーゼをコードの供給源生物体を含め対応する遺伝子のための供給源生物体として利用可能である他の例示的な種が含まれる。しかし、完全ゲノム配列が現在、395種の微生物のゲノム、ならびに多様な酵母、真菌、植物および哺乳動物のゲノムを含めて、550超の種について利用可能である(これらの半分超が公共のデータベース、例として、NCBI上で利用可能である)ので、例えば、公知の遺伝子のホモログ、オルソログ、パラログおよび非オルソロガス遺伝子の置換物を含めた、関係のあるまたは離れた種における1つまたは複数の遺伝子について、3-HBal、1,3-BDO、4-HBalもしくは1,4-BDOの生合成活性をコードする遺伝子を同定すること、ならびに生物体間で遺伝子変化物(genetic alteration)を交換することは、当技術分野で日常的であり、周知である。したがって、特定の生物体、例として、E.coliに言及して本明細書に記載する、本発明のアルデヒドデヒドロゲナーゼの発現を含め、3-HBal、1,3-BDO、4-HBalもしくは1,4-BDOもしくはそれに関連する下流生成物、例として、そのエステルもしくはアミドの生合成を可能にする代謝変化は、原核生物および真核生物を一様に含めた、他の微生物に容易に適用することができる。本明細書において提供される教示および手引きを考慮すると、1つの生物体において例示される代謝変化を、他の細胞、例として、生物体に等しく適用することができることを当業者は知る。
2CO2+4H2+nADP+nPi→CH3COOH+2H2O+nATP
したがって、Wood-Ljungdahl経路を有する天然に存在しない微生物は、アセチルCoAおよび他の所望の生成物の生成にCO2およびH2混合物も利用することができる。
この実施例では、望ましい特性を有するアルデヒドデヒドロゲナーゼバリアントの生成を記載する。
Claims (1)
- 明細書に記載の発明。
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201762480194P | 2017-03-31 | 2017-03-31 | |
US62/480,194 | 2017-03-31 | ||
JP2019553009A JP2020515255A (ja) | 2017-03-31 | 2018-03-29 | アルデヒドデヒドロゲナーゼバリアントおよび使用の方法 |
PCT/US2018/025122 WO2018183664A1 (en) | 2017-03-31 | 2018-03-29 | Aldehyde dehydrogenase variants and methods of use |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019553009A Division JP2020515255A (ja) | 2017-03-31 | 2018-03-29 | アルデヒドデヒドロゲナーゼバリアントおよび使用の方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2022159411A true JP2022159411A (ja) | 2022-10-17 |
Family
ID=62002473
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019553009A Pending JP2020515255A (ja) | 2017-03-31 | 2018-03-29 | アルデヒドデヒドロゲナーゼバリアントおよび使用の方法 |
JP2022127874A Pending JP2022159411A (ja) | 2017-03-31 | 2022-08-10 | アルデヒドデヒドロゲナーゼバリアントおよび使用の方法 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019553009A Pending JP2020515255A (ja) | 2017-03-31 | 2018-03-29 | アルデヒドデヒドロゲナーゼバリアントおよび使用の方法 |
Country Status (9)
Country | Link |
---|---|
US (2) | US11299716B2 (ja) |
EP (1) | EP3601546A1 (ja) |
JP (2) | JP2020515255A (ja) |
KR (2) | KR20240033193A (ja) |
CN (1) | CN110730820A (ja) |
AU (1) | AU2018244459A1 (ja) |
BR (1) | BR112019020461A2 (ja) |
CA (1) | CA3058219A1 (ja) |
WO (1) | WO2018183664A1 (ja) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2510102A4 (en) * | 2009-12-10 | 2014-01-22 | Genomatica Inc | METHODS AND ORGANIZATIONS FOR THE CONVERSION OF SYNTHESIS GAS OR OTHER CARBONACEOUS GAS SOURCES AND METHANOL TO 1,3-BUTANEDIOL |
EP3601547A1 (en) | 2017-03-31 | 2020-02-05 | Genomatica, Inc. | 3-hydroxybutyryl-coa dehydrogenase variants and methods of use |
EP3856896A1 (en) * | 2018-09-26 | 2021-08-04 | Genomatica, Inc. | Aldehyde dehydrogenase variants and methods of using same |
CN112280722B (zh) * | 2019-07-23 | 2022-03-08 | 清华大学 | 用于生产光学纯1,3-丁二醇的重组菌及其应用 |
US20210403841A1 (en) * | 2020-03-12 | 2021-12-30 | Poet Research, Inc. | Enzymatic degradation of mycotoxins during grain processing |
CN112481229B (zh) * | 2020-11-25 | 2022-12-30 | 华东理工大学 | 一种ω转氨酶及其突变体、重组质粒、基因工程菌及其应用 |
WO2023069952A1 (en) * | 2021-10-20 | 2023-04-27 | Genomatica, Inc. | Aldehyde dehydrogenase variants and methods of use |
Family Cites Families (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU3482200A (en) | 1999-02-02 | 2000-08-25 | Bernhard Palsson | Methods for identifying drug targets based on genomic sequence data |
JP4776146B2 (ja) | 2001-01-10 | 2011-09-21 | ザ・ペン・ステート・リサーチ・ファンデーション | 細胞代謝をモデル化する方法及びシステム |
US7127379B2 (en) | 2001-01-31 | 2006-10-24 | The Regents Of The University Of California | Method for the evolutionary design of biochemical reaction networks |
EP1381860A4 (en) | 2001-03-01 | 2008-10-15 | Univ California | MODELS AND METHOD FOR DETERMINING SYSTEMIC PROPERTIES OF REGULATED RESPONSE NETWORKS |
US20030224363A1 (en) | 2002-03-19 | 2003-12-04 | Park Sung M. | Compositions and methods for modeling bacillus subtilis metabolism |
CA2480216A1 (en) | 2002-03-29 | 2003-10-09 | Genomatica, Inc. | Human metabolic models and methods |
US7856317B2 (en) | 2002-06-14 | 2010-12-21 | Genomatica, Inc. | Systems and methods for constructing genomic-based phenotypic models |
AU2003256480B2 (en) | 2002-07-10 | 2008-03-06 | The Penn State Research Foundation | Method for determining gene knockout strategies |
CA2500761C (en) | 2002-10-15 | 2012-11-20 | Bernhard O. Palsson | Methods and systems to identify operational reaction pathways |
WO2008115840A2 (en) | 2007-03-16 | 2008-09-25 | Genomatica, Inc. | Compositions and methods for the biosynthesis of 1,4-butanediol and its precursors |
US7947483B2 (en) | 2007-08-10 | 2011-05-24 | Genomatica, Inc. | Methods and organisms for the growth-coupled production of 1,4-butanediol |
WO2009023749A2 (en) | 2007-08-14 | 2009-02-19 | Frost, Inc. | Trolley assembly with non-rotatable axle |
CN101978042B (zh) | 2008-01-22 | 2017-03-08 | 基因组股份公司 | 利用合成气或其它气态碳源和甲醇的方法和有机体 |
WO2010030711A2 (en) | 2008-09-10 | 2010-03-18 | Genomatica, Inc. | Microorganisms for the production of 1,4-butanediol |
WO2010127319A2 (en) | 2009-04-30 | 2010-11-04 | Genomatica, Inc. | Organisms for the production of 1,3-butanediol |
US20100305519A1 (en) | 2009-06-02 | 2010-12-02 | Becton, Dickinson And Company | Cannula having an overlapping cannula feature and notch feature |
MY187676A (en) | 2009-06-04 | 2021-10-08 | Genomatica Inc | Microorganisms for the production of 1,4-butanediol and related methods |
CA2777459A1 (en) | 2009-10-13 | 2011-04-21 | Genomatica, Inc. | Microorganisms for the production of 1,4-butanediol, 4-hydroxybutanal, 4-hydroxybutyryl-coa, putrescine and related compounds, and methods related thereto |
EP2607340B1 (en) | 2010-07-26 | 2017-09-06 | Genomatica, Inc. | Microorganisms and methods for the biosynthesis of aromatics, 2,4-pentadienoate and 1,3-butadiene |
WO2012177943A1 (en) * | 2011-06-22 | 2012-12-27 | Genomatica, Inc. | Microorganisms for producing 1,4-butanediol and methods related thereto |
AU2012273177A1 (en) * | 2011-06-22 | 2013-05-02 | Genomatica, Inc. | Microorganisms for producing 1,3-butanediol and methods related thereto |
SG11201400466TA (en) | 2011-09-08 | 2014-04-28 | Genomatica Inc | Eukaryotic organisms and methods for producing 1,3-butanediol |
GB201206192D0 (en) | 2012-04-05 | 2012-05-23 | Tdeltas Ltd | Ketone bodies and ketone body esters and for maintaining or improving muscle power output |
TW201410865A (zh) | 2012-06-04 | 2014-03-16 | Genomatica Inc | 製造4-羥基丁酸酯、1,4-丁二醇及相關化合物之微生物及方法 |
CN102965401B (zh) | 2012-11-14 | 2014-01-01 | 中国科学院微生物研究所 | 1,2,4-丁三醇的生物合成方法 |
MY187966A (en) * | 2013-04-26 | 2021-11-02 | Genomatica Inc | Microorganisms and methods for production of 4-hydroxybutyrate, 1,4-butanediol and related compounds |
US11814664B2 (en) | 2013-05-24 | 2023-11-14 | Genomatica, Inc. | Microorganisms and methods for producing (3R)-hydroxybutyl (3R)-hydroxybutyrate |
WO2014207099A1 (en) * | 2013-06-26 | 2014-12-31 | Abengoa Bioenergia Nuevas Tecnologias S.A. | Anoxic biological production of fuels and of bulk chemicals from second generation feedstocks |
KR20150115289A (ko) * | 2014-04-03 | 2015-10-14 | 삼성전자주식회사 | 알데히드 데히드로게나제 변이체, 상기 변이체를 코딩하는 폴리뉴클레오티드, 상기 폴리뉴클레오티드를 포함하는 벡터 및 미생물, 및 이를 이용한 1,4-부탄디올의 생산방법 |
EP3601547A1 (en) | 2017-03-31 | 2020-02-05 | Genomatica, Inc. | 3-hydroxybutyryl-coa dehydrogenase variants and methods of use |
US20210101855A1 (en) | 2017-03-31 | 2021-04-08 | Genomatica, Inc. | Process and systems for obtaining 1,3-butanediol from fermentation broths |
-
2018
- 2018-03-29 CN CN201880036524.2A patent/CN110730820A/zh active Pending
- 2018-03-29 KR KR1020247007426A patent/KR20240033193A/ko active Search and Examination
- 2018-03-29 AU AU2018244459A patent/AU2018244459A1/en active Pending
- 2018-03-29 BR BR112019020461A patent/BR112019020461A2/pt unknown
- 2018-03-29 US US16/499,531 patent/US11299716B2/en active Active
- 2018-03-29 CA CA3058219A patent/CA3058219A1/en active Pending
- 2018-03-29 WO PCT/US2018/025122 patent/WO2018183664A1/en active Application Filing
- 2018-03-29 EP EP18718343.9A patent/EP3601546A1/en active Pending
- 2018-03-29 KR KR1020197032015A patent/KR102645531B1/ko active IP Right Grant
- 2018-03-29 JP JP2019553009A patent/JP2020515255A/ja active Pending
-
2022
- 2022-03-17 US US17/697,504 patent/US20220325254A1/en active Pending
- 2022-08-10 JP JP2022127874A patent/JP2022159411A/ja active Pending
Also Published As
Publication number | Publication date |
---|---|
WO2018183664A1 (en) | 2018-10-04 |
KR20190134706A (ko) | 2019-12-04 |
US20200040312A1 (en) | 2020-02-06 |
US20220325254A1 (en) | 2022-10-13 |
CN110730820A (zh) | 2020-01-24 |
CA3058219A1 (en) | 2018-10-04 |
AU2018244459A1 (en) | 2019-10-10 |
JP2020515255A (ja) | 2020-05-28 |
KR102645531B1 (ko) | 2024-03-11 |
KR20240033193A (ko) | 2024-03-12 |
BR112019020461A2 (pt) | 2020-06-09 |
US11299716B2 (en) | 2022-04-12 |
EP3601546A1 (en) | 2020-02-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2022159411A (ja) | アルデヒドデヒドロゲナーゼバリアントおよび使用の方法 | |
DK2679676T3 (en) | PROCEDURES AND ORGANISMS FOR THE GROWTH-LINKED PREPARATION OF 1,4-BUTANDIOL | |
KR20120036851A (ko) | 사이클로헥사논의 제조를 위한 유기체 | |
US20230416698A1 (en) | Aldehyde dehydrogenase variants and methods of using same | |
AU2011209862A1 (en) | Microorganisms and methods for the biosynthesis of p-toluate and terephthalate | |
US20230139515A1 (en) | 3-hydroxybutyryl-coa dehydrogenase variants and methods of use | |
JP2023156360A (ja) | キシリトールを生産するメチニコビア種 | |
US20210079334A1 (en) | Fermentation systems and methods with substantially uniform volumetric uptake rate of a reactive gaseous component | |
US20220403420A1 (en) | Microorganisms and methods for increasing co-factors | |
US20230287435A1 (en) | Microorganisms and methods for reducing by-products | |
WO2023069957A1 (en) | Aldehyde dehydrogenase variants and methods of use | |
WO2023069952A1 (en) | Aldehyde dehydrogenase variants and methods of use | |
AU2013202614A1 (en) | Microorganisms and methods for the biosynthesis of P-toluate and terephthalate |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20220810 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230802 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20231102 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20240131 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20240426 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20240628 |