WO2022231370A1 - Nouveau variant bifonctionnel de la phosphoribosylaminoimidazolecarboxamide formyltransférase/imp cyclohydrolase et procédé de production d'imp au moyen de celui-ci - Google Patents
Nouveau variant bifonctionnel de la phosphoribosylaminoimidazolecarboxamide formyltransférase/imp cyclohydrolase et procédé de production d'imp au moyen de celui-ci Download PDFInfo
- Publication number
- WO2022231370A1 WO2022231370A1 PCT/KR2022/006152 KR2022006152W WO2022231370A1 WO 2022231370 A1 WO2022231370 A1 WO 2022231370A1 KR 2022006152 W KR2022006152 W KR 2022006152W WO 2022231370 A1 WO2022231370 A1 WO 2022231370A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- present application
- polypeptide
- imp
- strain
- sequence
- Prior art date
Links
- 102100020796 Inosine 5'-monophosphate cyclohydrolase Human genes 0.000 title claims abstract description 35
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 34
- 230000001588 bifunctional effect Effects 0.000 title claims abstract description 33
- 101001138523 Homo sapiens Inosine 5'-monophosphate cyclohydrolase Proteins 0.000 title claims abstract description 28
- 229920001184 polypeptide Polymers 0.000 claims description 111
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 111
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 111
- 108091033319 polynucleotide Proteins 0.000 claims description 102
- 102000040430 polynucleotide Human genes 0.000 claims description 102
- 239000002157 polynucleotide Substances 0.000 claims description 102
- 235000001014 amino acid Nutrition 0.000 claims description 24
- 150000001413 amino acids Chemical group 0.000 claims description 24
- 241000186216 Corynebacterium Species 0.000 claims description 21
- 230000001965 increasing effect Effects 0.000 claims description 16
- 238000012258 culturing Methods 0.000 claims description 12
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 9
- 239000004474 valine Substances 0.000 claims description 9
- 235000004279 alanine Nutrition 0.000 claims description 7
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 6
- 241000186308 Corynebacterium stationis Species 0.000 abstract description 7
- 230000000694 effects Effects 0.000 description 67
- 235000013902 inosinic acid Nutrition 0.000 description 56
- RQFCJASXJCIDSX-UHFFFAOYSA-N 14C-Guanosin-5'-monophosphat Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(COP(O)(O)=O)C(O)C1O RQFCJASXJCIDSX-UHFFFAOYSA-N 0.000 description 54
- GRSZFWQUAKGDAV-KQYNXXCUSA-N IMP Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(NC=NC2=O)=C2N=C1 GRSZFWQUAKGDAV-KQYNXXCUSA-N 0.000 description 54
- GRSZFWQUAKGDAV-UHFFFAOYSA-N Inosinic acid Natural products OC1C(O)C(COP(O)(O)=O)OC1N1C(NC=NC2=O)=C2N=C1 GRSZFWQUAKGDAV-UHFFFAOYSA-N 0.000 description 54
- 244000005700 microbiome Species 0.000 description 47
- 108090000623 proteins and genes Proteins 0.000 description 39
- 125000003275 alpha amino acid group Chemical group 0.000 description 38
- 230000014509 gene expression Effects 0.000 description 36
- 239000013598 vector Substances 0.000 description 32
- 210000004027 cell Anatomy 0.000 description 25
- 239000002609 medium Substances 0.000 description 23
- 229940024606 amino acid Drugs 0.000 description 22
- 238000012986 modification Methods 0.000 description 22
- 230000004048 modification Effects 0.000 description 22
- 239000002773 nucleotide Substances 0.000 description 18
- 125000003729 nucleotide group Chemical group 0.000 description 18
- 210000000349 chromosome Anatomy 0.000 description 16
- 238000000034 method Methods 0.000 description 16
- 230000035772 mutation Effects 0.000 description 15
- 238000006467 substitution reaction Methods 0.000 description 12
- 108020004705 Codon Proteins 0.000 description 11
- 235000018102 proteins Nutrition 0.000 description 11
- 102000004169 proteins and genes Human genes 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 238000012217 deletion Methods 0.000 description 10
- 230000037430 deletion Effects 0.000 description 10
- 230000000295 complement effect Effects 0.000 description 9
- 108091081024 Start codon Proteins 0.000 description 8
- 238000003780 insertion Methods 0.000 description 8
- 230000037431 insertion Effects 0.000 description 8
- 239000003550 marker Substances 0.000 description 8
- 238000013518 transcription Methods 0.000 description 8
- 230000035897 transcription Effects 0.000 description 8
- 238000013519 translation Methods 0.000 description 8
- 108010007666 IMP cyclohydrolase Proteins 0.000 description 7
- 238000007792 addition Methods 0.000 description 7
- 238000009396 hybridization Methods 0.000 description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 238000004422 calculation algorithm Methods 0.000 description 6
- 230000001747 exhibiting effect Effects 0.000 description 6
- 239000001963 growth medium Substances 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 230000009466 transformation Effects 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 5
- 125000000539 amino acid group Chemical group 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000006801 homologous recombination Effects 0.000 description 5
- 238000002744 homologous recombination Methods 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 150000007523 nucleic acids Chemical class 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 4
- 108020003589 5' Untranslated Regions Proteins 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 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
- 108010072462 Hydroxymethyl and Formyl Transferases Proteins 0.000 description 4
- 102000006933 Hydroxymethyl and Formyl Transferases Human genes 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 108700026244 Open Reading Frames Proteins 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000002238 attenuated effect Effects 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 4
- 235000013379 molasses Nutrition 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 229930024421 Adenine Natural products 0.000 description 3
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 3
- 108020005544 Antisense RNA Proteins 0.000 description 3
- 229960000643 adenine Drugs 0.000 description 3
- 229940041514 candida albicans extract Drugs 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000003184 complementary RNA Substances 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 235000015097 nutrients Nutrition 0.000 description 3
- 230000002018 overexpression Effects 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 239000013587 production medium Substances 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000003827 upregulation Effects 0.000 description 3
- 239000012138 yeast extract Substances 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- ZBNZAJFNDPPMDT-UHFFFAOYSA-N 1h-imidazole-5-carboxamide Chemical compound NC(=O)C1=CNC=N1 ZBNZAJFNDPPMDT-UHFFFAOYSA-N 0.000 description 2
- DVNYTAVYBRSTGK-UHFFFAOYSA-N 5-aminoimidazole-4-carboxamide Chemical compound NC(=O)C=1N=CNC=1N DVNYTAVYBRSTGK-UHFFFAOYSA-N 0.000 description 2
- ABCOOORLYAOBOZ-KQYNXXCUSA-N 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide Chemical compound O=CNC1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(O)=O)O1 ABCOOORLYAOBOZ-KQYNXXCUSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 241000186145 Corynebacterium ammoniagenes Species 0.000 description 2
- 241000446654 Corynebacterium deserti Species 0.000 description 2
- 241001644925 Corynebacterium efficiens Species 0.000 description 2
- 241000186226 Corynebacterium glutamicum Species 0.000 description 2
- 241000291063 Corynebacterium halotolerans Species 0.000 description 2
- 241000128247 Corynebacterium pollutisoli Species 0.000 description 2
- 241000334675 Corynebacterium singulare Species 0.000 description 2
- 241000158523 Corynebacterium striatum Species 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- 239000005715 Fructose Substances 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
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 239000001888 Peptone Substances 0.000 description 2
- 108010080698 Peptones Proteins 0.000 description 2
- 108010045040 Phosphoribosylaminoimidazolecarboxamide formyltransferase Proteins 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 240000008042 Zea mays Species 0.000 description 2
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000000074 antisense oligonucleotide Substances 0.000 description 2
- 238000012230 antisense oligonucleotides Methods 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 235000005822 corn Nutrition 0.000 description 2
- 238000012136 culture method Methods 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 239000007857 degradation product Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 238000012239 gene modification Methods 0.000 description 2
- 230000005017 genetic modification Effects 0.000 description 2
- 235000013617 genetically modified food Nutrition 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 150000002484 inorganic compounds Chemical class 0.000 description 2
- 229910010272 inorganic material Inorganic materials 0.000 description 2
- 229910000358 iron sulfate Inorganic materials 0.000 description 2
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 229940099596 manganese sulfate Drugs 0.000 description 2
- 239000011702 manganese sulphate Substances 0.000 description 2
- 235000007079 manganese sulphate Nutrition 0.000 description 2
- SQQMAOCOWKFBNP-UHFFFAOYSA-L manganese(II) sulfate Chemical compound [Mn+2].[O-]S([O-])(=O)=O SQQMAOCOWKFBNP-UHFFFAOYSA-L 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 235000019319 peptone Nutrition 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 description 2
- 235000011009 potassium phosphates Nutrition 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000011218 seed culture Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 229960004793 sucrose Drugs 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- MSTNYGQPCMXVAQ-RYUDHWBXSA-N (6S)-5,6,7,8-tetrahydrofolic acid Chemical compound C([C@H]1CNC=2N=C(NC(=O)C=2N1)N)NC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 MSTNYGQPCMXVAQ-RYUDHWBXSA-N 0.000 description 1
- AUFGTPPARQZWDO-YPMHNXCESA-N 10-formyltetrahydrofolic acid Chemical compound C([C@H]1CNC=2N=C(NC(=O)C=2N1)N)N(C=O)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 AUFGTPPARQZWDO-YPMHNXCESA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 description 1
- 101150034533 ATIC gene Proteins 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 239000004254 Ammonium phosphate Substances 0.000 description 1
- 101100533902 Arabidopsis thaliana SPL13A gene Proteins 0.000 description 1
- 101100533904 Arabidopsis thaliana SPL13B gene Proteins 0.000 description 1
- 101100455080 Bacillus subtilis (strain 168) lmrB gene Proteins 0.000 description 1
- 238000010356 CRISPR-Cas9 genome editing Methods 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 241000186248 Corynebacterium callunae Species 0.000 description 1
- 241001605246 Corynebacterium crudilactis Species 0.000 description 1
- 241001134763 Corynebacterium flavescens Species 0.000 description 1
- 241000024402 Corynebacterium imitans Species 0.000 description 1
- 241000186249 Corynebacterium sp. Species 0.000 description 1
- 241000960580 Corynebacterium testudinoris Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 238000012270 DNA recombination Methods 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 108091092584 GDNA Proteins 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 239000004201 L-cysteine Substances 0.000 description 1
- 235000013878 L-cysteine Nutrition 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 108010021466 Mutant Proteins Proteins 0.000 description 1
- 102000008300 Mutant Proteins Human genes 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 101100070556 Oryza sativa subsp. japonica HSFA4D gene Proteins 0.000 description 1
- 101100043227 Oryza sativa subsp. japonica SPL13 gene Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 101150099282 SPL7 gene Proteins 0.000 description 1
- 240000000111 Saccharum officinarum Species 0.000 description 1
- 235000007201 Saccharum officinarum Nutrition 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 238000005377 adsorption chromatography Methods 0.000 description 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 229910000148 ammonium phosphate Inorganic materials 0.000 description 1
- 235000019289 ammonium phosphates Nutrition 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 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 1
- 229940000635 beta-alanine Drugs 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 229910000365 copper sulfate Inorganic materials 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 239000013601 cosmid vector Substances 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 235000013681 dietary sucrose Nutrition 0.000 description 1
- PXEDJBXQKAGXNJ-QTNFYWBSSA-L disodium L-glutamate Chemical compound [Na+].[Na+].[O-]C(=O)[C@@H](N)CCC([O-])=O PXEDJBXQKAGXNJ-QTNFYWBSSA-L 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000010230 functional analysis Methods 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 238000012226 gene silencing method Methods 0.000 description 1
- 238000012252 genetic analysis Methods 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 230000007614 genetic variation Effects 0.000 description 1
- 238000010362 genome editing Methods 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- FBAFATDZDUQKNH-UHFFFAOYSA-M iron chloride Chemical compound [Cl-].[Fe] FBAFATDZDUQKNH-UHFFFAOYSA-M 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 108091005573 modified proteins Proteins 0.000 description 1
- 102000035118 modified proteins Human genes 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 235000013923 monosodium glutamate Nutrition 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000001477 organic nitrogen group Chemical group 0.000 description 1
- -1 phosphoribosyl Chemical group 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 229920001522 polyglycol ester Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000007398 protein translocation Effects 0.000 description 1
- 101150103875 purH gene Proteins 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000002787 reinforcement Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000005185 salting out Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 230000037432 silent mutation Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229940073490 sodium glutamate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 239000005460 tetrahydrofolate Substances 0.000 description 1
- 229940086388 thiamine hydrochloride 5 mg Drugs 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 238000011426 transformation method Methods 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 101150062776 yccA gene Proteins 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
- 229960001763 zinc sulfate Drugs 0.000 description 1
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
- C12N9/10—Transferases (2.)
- C12N9/1003—Transferases (2.) transferring one-carbon groups (2.1)
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/74—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
- C12N15/77—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora for Corynebacterium; for Brevibacterium
-
- 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
- C12N9/14—Hydrolases (3)
- C12N9/78—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
-
- 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
- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/26—Preparation of nitrogen-containing carbohydrates
- C12P19/28—N-glycosides
- C12P19/30—Nucleotides
- C12P19/32—Nucleotides having a condensed ring system containing a six-membered ring having two N-atoms in the same ring, e.g. purine nucleotides, nicotineamide-adenine dinucleotide
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y201/00—Transferases transferring one-carbon groups (2.1)
- C12Y201/02—Hydroxymethyl-, formyl- and related transferases (2.1.2)
- C12Y201/02003—Phosphoribosylaminoimidazolecarboxamide formyltransferase (2.1.2.3), i.e. AICAR formyltransferase
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y305/00—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5)
- C12Y305/04—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5) in cyclic amidines (3.5.4)
- C12Y305/0401—IMP cyclohydrolase (3.5.4.10)
Definitions
- the present application is a novel bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase / IMP cyclohydrolase (bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase / IMP cyclohydrolase) variant, Corynebacterium stasis strain comprising the variant And it relates to a method for producing IMP using the strain.
- bifunctional phosphoribosylaminoimidazolecarboxa consisting of the amino acid sequence set forth in SEQ ID NO: 1, in which alanine, an amino acid corresponding to position 351 of the amino acid sequence of SEQ ID NO: 3, is substituted with valine
- a mutant of the mid formyltransferase/IMP cyclohydrolase (bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/IMP cyclohydrolase) is provided.
- bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/IMP cyclohydrolase refers to 10-formyltetrahydrofolate + 5-amino-1-(5 Phosphoribosylaminoimidazolecarboxamide formyltransferase, which catalyzes the chemical reaction of -phospho-D-ribosyl)imidazole-4-carboxamide ⁇ tetrahydrofolate + 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide (EC:2.1.2.3) and IMP + H 2 O ⁇ 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide catalyzing the chemical reaction of IMP cyclohydrolase (EC:3.5.4.10) containing two domains of activity.
- any amino acid sequence is aligned with SEQ ID NO: 3, and based on this, each amino acid residue of the amino acid sequence can be numbered with reference to the numerical position of the amino acid residue corresponding to the amino acid residue of SEQ ID NO: 3 .
- a sequence alignment algorithm such as that described in this application can identify the position of an amino acid, or a position at which modifications, such as substitutions, insertions, or deletions, occur compared to a query sequence (also referred to as a "reference sequence").
- the present invention is not limited thereto.
- the strain with increased IMP-producing ability of the present application may be a microorganism having increased IMP-producing ability compared to Corynebacterium stasis comprising the polypeptide of SEQ ID NO: 3 or a polynucleotide encoding the same, but is not limited thereto does not
- the target strain, bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/IMP cyclohydrolase unmodified microorganism is the CJI2332 strain (KCCM12277P, KR 10 -1950141 B1), but is not limited thereto.
- the recombinant strain with increased production capacity has an IMP production capacity of about 1.01 times or more, about 1.02 times or more, about 1.03 times or more, about 1.05 times or more, about 1.06 times or more, compared to the parent strain or unmodified microorganism before mutation.
- the microorganism of the present application is Corynebacterium glutamicum ( Corynebacterium glutamicum ), Corynebacterium crudilactis ), Corynebacterium deserti ( Corynebacterium deserti ), Cory Nebacterium efficiens ( Corynebacterium efficiens ), Corynebacterium callunae ), Corynebacterium stationis , Corynebacterium stationis ), Corynebacterium singulare ( Corynebacterium singulare ), Corynebacterium halo Tolerans ( Corynebacterium halotolerans ), Corynebacterium striatum ( Corynebacterium striatum ), Corynebacterium ammoniagenes ( Corynebacterium ammoniagenes ), Corynebacterium pollutisoli ( Corynebacterium pollutisoli ), Corynebacterium imitans imitans imitans imitans imit
- the increase in the intracellular copy number of the polynucleotide encoding the polypeptide is achieved by introduction into the host cell of a vector to which the polynucleotide encoding the polypeptide is operably linked, which can replicate and function independently of the host it may be Alternatively, the polynucleotide encoding the polypeptide may be achieved by introducing one copy or two or more copies into a chromosome in a host cell.
- the introduction into the chromosome may be performed by introducing a vector capable of inserting the polynucleotide into the chromosome in the host cell into the host cell, but is not limited thereto.
- the vector is the same as described above.
- Codon optimization of the polynucleotide encoding the polypeptide is codon-optimized so that the transcription or translation of the endogenous polynucleotide is increased in the host cell, or the transcription and translation of the foreign polynucleotide is optimized in the host cell. It may be that its codons are optimized so that the
- nitrogen source examples include inorganic nitrogen sources such as ammonia, ammonium sulfate, ammonium chloride, ammonium acetate, ammonium phosphate, anmonium carbonate, and ammonium nitrate; Amino acids such as glutamic acid, methionine, glutamine, and organic nitrogen sources such as peptone, NZ-amine, meat extract, yeast extract, malt extract, corn steep liquor, casein hydrolyzate, fish or degradation products thereof, defatted soybean cake or degradation products thereof, etc. can be used These nitrogen sources may be used alone or in combination of two or more, but is not limited thereto.
- inorganic nitrogen sources such as ammonia, ammonium sulfate, ammonium chloride, ammonium acetate, ammonium phosphate, anmonium carbonate, and ammonium nitrate
- Amino acids such as glutamic acid, methionine, glutamine
- organic nitrogen sources such as peptone, NZ-amine, meat extract, yeast extract
- the vector for the production of the expression strain was prepared as follows using the plasmid pDCM2 (Korea Publication No. 10-2020-0136813) for the insertion and replacement of genes in the Corynebacterium chromosome.
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Plant Pathology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (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)
Abstract
La présente invention concerne un nouveau variant bifonctionnel de la phosphoribosylaminoimidazolecarboxamide formyltransférase/IMP cyclohydrolase, une souche de Corynebacterium stationis comprenant ce variant et un procédé de production d'IMP au moyen de cette souche.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR10-2021-0055704 | 2021-04-29 | ||
| KR1020210055704A KR102277409B1 (ko) | 2021-04-29 | 2021-04-29 | 신규한 2중기능성 포스포리보실아미노이미다졸카르복사미드 포밀트랜스퍼라아제/imp 사이클로하이드롤라아제 변이체 및 이를 이용한 imp 생산 방법 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2022231370A1 true WO2022231370A1 (fr) | 2022-11-03 |
Family
ID=76862729
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/KR2022/006152 WO2022231370A1 (fr) | 2021-04-29 | 2022-04-29 | Nouveau variant bifonctionnel de la phosphoribosylaminoimidazolecarboxamide formyltransférase/imp cyclohydrolase et procédé de production d'imp au moyen de celui-ci |
Country Status (2)
| Country | Link |
|---|---|
| KR (1) | KR102277409B1 (fr) |
| WO (1) | WO2022231370A1 (fr) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102277409B1 (ko) * | 2021-04-29 | 2021-07-14 | 씨제이제일제당 주식회사 | 신규한 2중기능성 포스포리보실아미노이미다졸카르복사미드 포밀트랜스퍼라아제/imp 사이클로하이드롤라아제 변이체 및 이를 이용한 imp 생산 방법 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20090114456A (ko) * | 2007-02-20 | 2009-11-03 | 아지노모토 가부시키가이샤 | Ｌ-아미노산 또는 핵산의 제조방법 |
| KR20100109732A (ko) * | 2009-04-01 | 2010-10-11 | 씨제이제일제당 (주) | 5'-이노신산 생산성이 향상된 코리네박테리움 속 미생물 및 이를 이용한 핵산의 생산방법 |
| KR20160078694A (ko) * | 2014-12-24 | 2016-07-05 | 대상 주식회사 | 5’-이노신산의 고생성능 코리네박테리움 암모니아게네스 변이 균주 및 이를 이용한 5’-이노신산의 제조 방법 |
| KR101916611B1 (ko) * | 2017-12-15 | 2018-11-07 | 씨제이제일제당 (주) | 신규 폴리펩타이드 및 이를 이용한 imp 생산방법 |
| KR102277409B1 (ko) * | 2021-04-29 | 2021-07-14 | 씨제이제일제당 주식회사 | 신규한 2중기능성 포스포리보실아미노이미다졸카르복사미드 포밀트랜스퍼라아제/imp 사이클로하이드롤라아제 변이체 및 이를 이용한 imp 생산 방법 |
-
2021
- 2021-04-29 KR KR1020210055704A patent/KR102277409B1/ko active IP Right Grant
-
2022
- 2022-04-29 WO PCT/KR2022/006152 patent/WO2022231370A1/fr active Application Filing
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20090114456A (ko) * | 2007-02-20 | 2009-11-03 | 아지노모토 가부시키가이샤 | Ｌ-아미노산 또는 핵산의 제조방법 |
| KR20100109732A (ko) * | 2009-04-01 | 2010-10-11 | 씨제이제일제당 (주) | 5'-이노신산 생산성이 향상된 코리네박테리움 속 미생물 및 이를 이용한 핵산의 생산방법 |
| KR20160078694A (ko) * | 2014-12-24 | 2016-07-05 | 대상 주식회사 | 5’-이노신산의 고생성능 코리네박테리움 암모니아게네스 변이 균주 및 이를 이용한 5’-이노신산의 제조 방법 |
| KR101916611B1 (ko) * | 2017-12-15 | 2018-11-07 | 씨제이제일제당 (주) | 신규 폴리펩타이드 및 이를 이용한 imp 생산방법 |
| KR102277409B1 (ko) * | 2021-04-29 | 2021-07-14 | 씨제이제일제당 주식회사 | 신규한 2중기능성 포스포리보실아미노이미다졸카르복사미드 포밀트랜스퍼라아제/imp 사이클로하이드롤라아제 변이체 및 이를 이용한 imp 생산 방법 |
Non-Patent Citations (1)
| Title |
|---|
| DATABASE Protein GenPept; ANONYMOUS : "bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase -", XP055982273, retrieved from NCBI * |
Also Published As
| Publication number | Publication date |
|---|---|
| KR102277409B1 (ko) | 2021-07-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO2022231369A1 (fr) | Nouveau variant de la phosphoribosylglycinamide formyltransférase dépendant des formiates et procédé de production d'imp au moyen de celui-ci | |
| WO2022231368A1 (fr) | Nouveau variant de la sous-unité alpha de la glutamate synthase et procédé de production d'acide l-glutamique au moyen de celui-ci | |
| WO2022225322A1 (fr) | Nouvelle variante alpha de la sous-unité alpha de f0f1 atp synthase et procédé de production de xmp ou gmp l'utilisant | |
| WO2022231370A1 (fr) | Nouveau variant bifonctionnel de la phosphoribosylaminoimidazolecarboxamide formyltransférase/imp cyclohydrolase et procédé de production d'imp au moyen de celui-ci | |
| WO2022231371A1 (fr) | Nouveau mutant de la 5-(carboxyamino)imidazole ribonucléotide synthétase et procédé de production d'imp au moyen de celui-ci | |
| WO2022154177A1 (fr) | Nouveau variant d'acylhydrolase 3d-(3,5/4)-trihydroxycyclohexane-1,2-dione et procédé de production d'imp l'utilisant | |
| WO2022154178A1 (fr) | Nouveau variant de coproporphyrinogène iii oxydase anaérobie et procédé de production d'imp l'utilisant | |
| WO2022154181A1 (fr) | Nouvelle variante de l'enzyme de ramification du 1,4-alpha-glucane et procédé de production d'imp faisant appel à celle-ci | |
| WO2022154191A1 (fr) | Nouveau variant de réductase d'acide 2,5-dicéto-d-gluconique et procédé de production de xmp ou gmp l'utilisant | |
| WO2022154190A1 (fr) | Nouveau variant d'hydrolase de phosphonoacétate et procédé de production de xmp ou de gmp l'utilisant | |
| WO2022225321A1 (fr) | Nouveau variant de la sous-unité gamma de la f0f1 atp synthase et procédé de production de xmp ou de gmp au moyen de celui-ci | |
| WO2022225319A1 (fr) | Nouveau variant de l-sérine ammoniac-lyase et procédé de production de xmp ou de gmp au moyen de celui-ci | |
| WO2022225320A1 (fr) | Nouveau variant de la phosphoglycérate déshydrogénase et procédé de production de xap ou de gmp au moyen de celui-ci | |
| WO2022163920A1 (fr) | Nouveau variant de cystéine sulfinate désulfinase et procédé de production de l-valine l'utilisant | |
| WO2022231067A1 (fr) | Nouveau variant d'uracil phosphoribosyltransférase/régulateur de transcription de l'opéron pyr bifonctionnel et procédé de production d'imp l'utilisant | |
| WO2022225100A1 (fr) | Nouveau variant bifonctionnel de méthylènetétrahydrofolate déshydrogénase/méthényltétrahydrofolate cyclohydrolase et procédé de production de xmp ou gmp l'utilisant | |
| WO2022154179A1 (fr) | Nouvelle variante de la d-alanine—d-alanine ligase, et procédé de production d'imp faisant appel à celle-ci | |
| WO2022154185A1 (fr) | Nouveau variant de méthionine sulfoxyde réductase peptidique et procédé de production d'imp au moyen de celui-ci | |
| WO2022154186A1 (fr) | Nouveau variant de phytoène désaturase, et procédé de production d'imp l'utilisant | |
| WO2022163932A1 (fr) | Nouveau variant d'aldéhyde déshydrogénase et procédé de production de xmp ou gmp l'utilisant | |
| WO2022154182A1 (fr) | Nouvelle variante de la formimidoylglutamase et procédé de production d'imp faisant appel à celle-ci | |
| WO2022154180A1 (fr) | Nouveau variant de formamidopyrimidine-adn glycosylase et procédé de production d'imp l'utilisant | |
| WO2022154183A1 (fr) | Nouveau variant de glucosamine-6-phosphate désaminase, et procédé de production d'imp l'utilisant | |
| WO2022154192A1 (fr) | Nouveau variant d'aldéhyde déshydrogénase et procédé de production de xmp ou de gmp l'utilisant | |
| WO2022163930A1 (fr) | Nouveau variant de 2-succinyl-5-énolpyruvyl-6-hydroxy-3-cyclohexène-1-carboxylate synthase et procédé de production de xmp ou gmp l'utilisant |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 22796202 Country of ref document: EP Kind code of ref document: A1 |
|
| NENP | Non-entry into the national phase |
Ref country code: DE |
|
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 22796202 Country of ref document: EP Kind code of ref document: A1 |