JP4584242B2 - 改変されたニトリラーゼおよびカルボン酸の製造方法におけるその使用 - Google Patents
改変されたニトリラーゼおよびカルボン酸の製造方法におけるその使用 Download PDFInfo
- Publication number
- JP4584242B2 JP4584242B2 JP2006501937A JP2006501937A JP4584242B2 JP 4584242 B2 JP4584242 B2 JP 4584242B2 JP 2006501937 A JP2006501937 A JP 2006501937A JP 2006501937 A JP2006501937 A JP 2006501937A JP 4584242 B2 JP4584242 B2 JP 4584242B2
- Authority
- JP
- Japan
- Prior art keywords
- nitrilase
- acid
- amino acid
- sequence
- nucleic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 108010033272 Nitrilase Proteins 0.000 title claims abstract description 233
- 238000000034 method Methods 0.000 title claims abstract description 100
- 238000004519 manufacturing process Methods 0.000 title claims description 8
- 150000001735 carboxylic acids Chemical class 0.000 title abstract description 16
- 230000008569 process Effects 0.000 title description 20
- 150000007523 nucleic acids Chemical group 0.000 claims abstract description 113
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 70
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 65
- 150000001413 amino acids Chemical class 0.000 claims abstract description 62
- 229920001184 polypeptide Polymers 0.000 claims abstract description 62
- 150000002825 nitriles Chemical class 0.000 claims abstract description 54
- 241000588813 Alcaligenes faecalis Species 0.000 claims abstract description 52
- 230000014509 gene expression Effects 0.000 claims abstract description 50
- 229940005347 alcaligenes faecalis Drugs 0.000 claims abstract description 43
- 239000000758 substrate Substances 0.000 claims abstract description 32
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims abstract description 29
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims abstract description 16
- -1 tyrosine amino acid Chemical class 0.000 claims description 142
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 134
- 235000018417 cysteine Nutrition 0.000 claims description 77
- 102000039446 nucleic acids Human genes 0.000 claims description 62
- 108020004707 nucleic acids Proteins 0.000 claims description 62
- 235000001014 amino acid Nutrition 0.000 claims description 60
- 230000000694 effects Effects 0.000 claims description 59
- 235000004279 alanine Nutrition 0.000 claims description 58
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 57
- 229940024606 amino acid Drugs 0.000 claims description 57
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 51
- 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 claims description 47
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 45
- 239000002253 acid Substances 0.000 claims description 40
- 241000196324 Embryophyta Species 0.000 claims description 39
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 37
- 239000004473 Threonine Substances 0.000 claims description 23
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 21
- 235000009582 asparagine Nutrition 0.000 claims description 21
- 229960001230 asparagine Drugs 0.000 claims description 21
- 125000000539 amino acid group Chemical group 0.000 claims description 20
- ZECLJEYAWRQVIB-UHFFFAOYSA-N 2-(2-chlorophenyl)-2-hydroxyacetonitrile Chemical compound N#CC(O)C1=CC=CC=C1Cl ZECLJEYAWRQVIB-UHFFFAOYSA-N 0.000 claims description 19
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 19
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 19
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 18
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 18
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims description 16
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 14
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 14
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 13
- 235000004400 serine Nutrition 0.000 claims description 13
- 241000894006 Bacteria Species 0.000 claims description 12
- 150000001299 aldehydes Chemical class 0.000 claims description 12
- 238000003259 recombinant expression Methods 0.000 claims description 12
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 10
- 235000008729 phenylalanine Nutrition 0.000 claims description 10
- 239000004471 Glycine Substances 0.000 claims description 9
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 239000004009 herbicide Substances 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 150000002576 ketones Chemical class 0.000 claims description 7
- 125000001072 heteroaryl group Chemical group 0.000 claims description 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 4
- VITRCPVSCQOAFP-UHFFFAOYSA-N 2-(3-chlorophenyl)-2-hydroxyacetonitrile Chemical compound N#CC(O)C1=CC=CC(Cl)=C1 VITRCPVSCQOAFP-UHFFFAOYSA-N 0.000 claims description 4
- KKGXJLAWLSJRGK-UHFFFAOYSA-N 2-hydroxy-2-(4-methylphenyl)acetonitrile Chemical compound CC1=CC=C(C(O)C#N)C=C1 KKGXJLAWLSJRGK-UHFFFAOYSA-N 0.000 claims description 4
- 241000233866 Fungi Species 0.000 claims description 4
- 239000013604 expression vector Substances 0.000 claims description 4
- 230000012010 growth Effects 0.000 claims description 4
- 230000002363 herbicidal effect Effects 0.000 claims description 4
- IWYDHOAUDWTVEP-ZETCQYMHSA-N (S)-mandelic acid Chemical compound OC(=O)[C@@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-ZETCQYMHSA-N 0.000 claims description 3
- BJJDHOPCQJHYQH-UHFFFAOYSA-N 2-(2-bromophenyl)-2-hydroxyacetonitrile Chemical compound N#CC(O)C1=CC=CC=C1Br BJJDHOPCQJHYQH-UHFFFAOYSA-N 0.000 claims description 3
- UQYDMAISSWIIRF-UHFFFAOYSA-N 2-(3-bromophenyl)-2-hydroxyacetonitrile Chemical compound N#CC(O)C1=CC=CC(Br)=C1 UQYDMAISSWIIRF-UHFFFAOYSA-N 0.000 claims description 3
- LSDSHEPNJSMUTI-UHFFFAOYSA-N 2-(4-chlorophenyl)-2-hydroxyacetonitrile Chemical compound N#CC(O)C1=CC=C(Cl)C=C1 LSDSHEPNJSMUTI-UHFFFAOYSA-N 0.000 claims description 3
- KBPYNXCZRYZCTE-UHFFFAOYSA-N 2-hydroxy-2-(2-methylphenyl)acetonitrile Chemical compound CC1=CC=CC=C1C(O)C#N KBPYNXCZRYZCTE-UHFFFAOYSA-N 0.000 claims description 3
- QJOHNFPAIZBELI-UHFFFAOYSA-N 2-hydroxy-2-(3-methylphenyl)acetonitrile Chemical compound CC1=CC=CC(C(O)C#N)=C1 QJOHNFPAIZBELI-UHFFFAOYSA-N 0.000 claims description 3
- 241000588722 Escherichia Species 0.000 claims description 3
- 241000187654 Nocardia Species 0.000 claims description 3
- IWYDHOAUDWTVEP-SSDOTTSWSA-N (R)-mandelic acid Chemical compound OC(=O)[C@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-SSDOTTSWSA-N 0.000 claims description 2
- 241000186359 Mycobacterium Species 0.000 claims description 2
- 241000316848 Rhodococcus <scale insect> Species 0.000 claims description 2
- 241000187747 Streptomyces Species 0.000 claims description 2
- 230000009471 action Effects 0.000 claims description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 claims 1
- 241000195493 Cryptophyta Species 0.000 claims 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 claims 1
- 229960002510 mandelic acid Drugs 0.000 claims 1
- 150000002826 nitrites Chemical class 0.000 claims 1
- 239000013598 vector Substances 0.000 abstract description 32
- 244000005700 microbiome Species 0.000 abstract description 18
- ODKSFYDXXFIFQN-UHFFFAOYSA-N Arginine Chemical compound OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 78
- 108090000623 proteins and genes Proteins 0.000 description 48
- 239000004475 Arginine Substances 0.000 description 40
- 125000003275 alpha amino acid group Chemical group 0.000 description 32
- 102000004190 Enzymes Human genes 0.000 description 30
- 108090000790 Enzymes Proteins 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 30
- 229940088598 enzyme Drugs 0.000 description 30
- 108020004414 DNA Proteins 0.000 description 29
- 210000004027 cell Anatomy 0.000 description 29
- NNICRUQPODTGRU-UHFFFAOYSA-N mandelonitrile Chemical class N#CC(O)C1=CC=CC=C1 NNICRUQPODTGRU-UHFFFAOYSA-N 0.000 description 28
- HNDVDQJCIGZPNO-UHFFFAOYSA-N Histidine Chemical compound OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 26
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 25
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 25
- 235000018102 proteins Nutrition 0.000 description 25
- 102000004169 proteins and genes Human genes 0.000 description 25
- 230000001105 regulatory effect Effects 0.000 description 24
- 239000000047 product Substances 0.000 description 20
- 238000002703 mutagenesis Methods 0.000 description 18
- 231100000350 mutagenesis Toxicity 0.000 description 18
- 230000035772 mutation Effects 0.000 description 18
- 230000015572 biosynthetic process Effects 0.000 description 16
- 239000013612 plasmid Substances 0.000 description 16
- 229960003767 alanine Drugs 0.000 description 15
- 125000003729 nucleotide group Chemical group 0.000 description 15
- 150000007513 acids Chemical class 0.000 description 14
- 239000002609 medium Substances 0.000 description 14
- 238000006467 substitution reaction Methods 0.000 description 14
- 238000003786 synthesis reaction Methods 0.000 description 14
- 108020004705 Codon Proteins 0.000 description 13
- 241000588724 Escherichia coli Species 0.000 description 13
- 229960002433 cysteine Drugs 0.000 description 13
- 230000002068 genetic effect Effects 0.000 description 13
- 239000002773 nucleotide Substances 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 12
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 235000013922 glutamic acid Nutrition 0.000 description 12
- 239000004220 glutamic acid Substances 0.000 description 12
- 238000009396 hybridization Methods 0.000 description 12
- 230000004048 modification Effects 0.000 description 11
- 238000012986 modification Methods 0.000 description 11
- 238000002864 sequence alignment Methods 0.000 description 11
- 230000009466 transformation Effects 0.000 description 11
- 108091035707 Consensus sequence Proteins 0.000 description 10
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 10
- 239000004472 Lysine Substances 0.000 description 10
- 230000001965 increasing effect Effects 0.000 description 10
- 238000002741 site-directed mutagenesis Methods 0.000 description 10
- 125000000217 alkyl group Chemical group 0.000 description 9
- OZDAOHVKBFBBMZ-UHFFFAOYSA-N 2-aminopentanedioic acid;hydrate Chemical compound O.OC(=O)C(N)CCC(O)=O OZDAOHVKBFBBMZ-UHFFFAOYSA-N 0.000 description 8
- 229960000723 ampicillin Drugs 0.000 description 8
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 8
- 239000012634 fragment Substances 0.000 description 8
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 238000005215 recombination Methods 0.000 description 8
- 230000006798 recombination Effects 0.000 description 8
- 229960001153 serine Drugs 0.000 description 8
- 238000013519 translation Methods 0.000 description 8
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 7
- 241000187693 Rhodococcus rhodochrous Species 0.000 description 7
- 238000013459 approach Methods 0.000 description 7
- 229960005091 chloramphenicol Drugs 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 238000002425 crystallisation Methods 0.000 description 7
- 230000008025 crystallization Effects 0.000 description 7
- 238000000855 fermentation Methods 0.000 description 7
- 230000004151 fermentation Effects 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 229960000310 isoleucine Drugs 0.000 description 7
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 102000040430 polynucleotide Human genes 0.000 description 7
- 108091033319 polynucleotide Proteins 0.000 description 7
- 239000002157 polynucleotide Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 229960000268 spectinomycin Drugs 0.000 description 7
- UNFWWIHTNXNPBV-WXKVUWSESA-N spectinomycin Chemical compound O([C@@H]1[C@@H](NC)[C@@H](O)[C@H]([C@@H]([C@H]1O1)O)NC)[C@]2(O)[C@H]1O[C@H](C)CC2=O UNFWWIHTNXNPBV-WXKVUWSESA-N 0.000 description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 6
- 108091026890 Coding region Proteins 0.000 description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 241000589516 Pseudomonas Species 0.000 description 6
- 241000589774 Pseudomonas sp. Species 0.000 description 6
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 6
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 6
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 6
- 235000003704 aspartic acid Nutrition 0.000 description 6
- 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 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
- 229910052794 bromium Inorganic materials 0.000 description 6
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000010367 cloning Methods 0.000 description 6
- 125000004122 cyclic group Chemical group 0.000 description 6
- 239000011737 fluorine Substances 0.000 description 6
- 229910052731 fluorine Inorganic materials 0.000 description 6
- 230000004927 fusion Effects 0.000 description 6
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000011159 matrix material Substances 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 241000894007 species Species 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 241000589158 Agrobacterium Species 0.000 description 5
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 5
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N Glutamine Chemical compound OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 5
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 5
- PNNNRSAQSRJVSB-UHFFFAOYSA-N L-rhamnose Natural products CC(O)C(O)C(O)C(O)C=O PNNNRSAQSRJVSB-UHFFFAOYSA-N 0.000 description 5
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 5
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 5
- 238000007792 addition Methods 0.000 description 5
- 125000003342 alkenyl group Chemical group 0.000 description 5
- 125000003545 alkoxy group Chemical group 0.000 description 5
- 238000004422 calculation algorithm Methods 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 230000002255 enzymatic effect Effects 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 238000005755 formation reaction Methods 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 229930182817 methionine Natural products 0.000 description 5
- 238000010369 molecular cloning Methods 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 229960005190 phenylalanine Drugs 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 238000011144 upstream manufacturing Methods 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- CKLJMWTZIZZHCS-UHFFFAOYSA-N Aspartic acid Chemical compound OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 241000206602 Eukaryota Species 0.000 description 4
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Chemical compound OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 4
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- 108091081024 Start codon Proteins 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000033228 biological regulation Effects 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N methyl cyanide Natural products CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 238000012163 sequencing technique Methods 0.000 description 4
- 229960002898 threonine Drugs 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- AYTVNJIUMVFUCJ-UHFFFAOYSA-N 2-(4-bromophenyl)-2-hydroxyacetonitrile Chemical compound N#CC(O)C1=CC=C(Br)C=C1 AYTVNJIUMVFUCJ-UHFFFAOYSA-N 0.000 description 3
- UPMXNNIRAGDFEH-UHFFFAOYSA-N 3,5-dibromo-4-hydroxybenzonitrile Chemical compound OC1=C(Br)C=C(C#N)C=C1Br UPMXNNIRAGDFEH-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241000588986 Alcaligenes Species 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 241000193830 Bacillus <bacterium> Species 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 241000186216 Corynebacterium Species 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 3
- 241000235648 Pichia Species 0.000 description 3
- 239000004098 Tetracycline Substances 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000005090 alkenylcarbonyl group Chemical group 0.000 description 3
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 239000006285 cell suspension Substances 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 108020001507 fusion proteins Proteins 0.000 description 3
- 102000037865 fusion proteins Human genes 0.000 description 3
- 229960002743 glutamine Drugs 0.000 description 3
- 235000004554 glutamine Nutrition 0.000 description 3
- 229960002449 glycine Drugs 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 3
- 229930027917 kanamycin Natural products 0.000 description 3
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 3
- 229960000318 kanamycin Drugs 0.000 description 3
- 229930182823 kanamycin A Natural products 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 229960002180 tetracycline Drugs 0.000 description 3
- 229930101283 tetracycline Natural products 0.000 description 3
- 235000019364 tetracycline Nutrition 0.000 description 3
- 150000003522 tetracyclines Chemical class 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 238000001890 transfection Methods 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
- LWTDZKXXJRRKDG-KXBFYZLASA-N (-)-phaseollin Chemical compound C1OC2=CC(O)=CC=C2[C@H]2[C@@H]1C1=CC=C3OC(C)(C)C=CC3=C1O2 LWTDZKXXJRRKDG-KXBFYZLASA-N 0.000 description 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 2
- SDADKJCPTQNFRZ-UHFFFAOYSA-N 2-(2-fluorophenyl)-2-hydroxyacetonitrile Chemical compound N#CC(O)C1=CC=CC=C1F SDADKJCPTQNFRZ-UHFFFAOYSA-N 0.000 description 2
- PIUFDVZAZWZBCK-UHFFFAOYSA-N 2-(3-fluorophenyl)-2-hydroxyacetonitrile Chemical compound N#CC(O)C1=CC=CC(F)=C1 PIUFDVZAZWZBCK-UHFFFAOYSA-N 0.000 description 2
- UWDPUVCVIQXYQR-UHFFFAOYSA-N 2-(4-fluorophenyl)-2-hydroxyacetonitrile Chemical compound N#CC(O)C1=CC=C(F)C=C1 UWDPUVCVIQXYQR-UHFFFAOYSA-N 0.000 description 2
- UYOPHIQZIDOLKF-UHFFFAOYSA-N 2-hydroxy-2-(2-methoxyphenyl)acetonitrile Chemical compound COC1=CC=CC=C1C(O)C#N UYOPHIQZIDOLKF-UHFFFAOYSA-N 0.000 description 2
- YIBWLYSNBNNELO-UHFFFAOYSA-N 2-hydroxy-2-(2-nitrophenyl)acetonitrile Chemical compound N#CC(O)C1=CC=CC=C1[N+]([O-])=O YIBWLYSNBNNELO-UHFFFAOYSA-N 0.000 description 2
- XDOJPCPGMDHJAA-UHFFFAOYSA-N 2-hydroxy-2-(3-methoxyphenyl)acetonitrile Chemical compound COC1=CC=CC(C(O)C#N)=C1 XDOJPCPGMDHJAA-UHFFFAOYSA-N 0.000 description 2
- IBMWJEGPSVVIOM-UHFFFAOYSA-N 2-hydroxy-2-(3-nitrophenyl)acetonitrile Chemical compound N#CC(O)C1=CC=CC([N+]([O-])=O)=C1 IBMWJEGPSVVIOM-UHFFFAOYSA-N 0.000 description 2
- WLDAAMXETLHTER-UHFFFAOYSA-N 2-hydroxy-2-(4-methoxyphenyl)acetonitrile Chemical compound COC1=CC=C(C(O)C#N)C=C1 WLDAAMXETLHTER-UHFFFAOYSA-N 0.000 description 2
- OVXMNRYLZWZZFE-UHFFFAOYSA-N 2-hydroxy-2-(4-nitrophenyl)acetonitrile Chemical compound N#CC(O)C1=CC=C([N+]([O-])=O)C=C1 OVXMNRYLZWZZFE-UHFFFAOYSA-N 0.000 description 2
- 108010020183 3-phosphoshikimate 1-carboxyvinyltransferase Proteins 0.000 description 2
- 241000588625 Acinetobacter sp. Species 0.000 description 2
- 241001156002 Anthonomus pomorum Species 0.000 description 2
- 108030005367 Arylacetonitrilases Proteins 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 239000002028 Biomass Substances 0.000 description 2
- 241000186146 Brevibacterium Species 0.000 description 2
- 239000005489 Bromoxynil Substances 0.000 description 2
- QCMYYKRYFNMIEC-UHFFFAOYSA-N COP(O)=O Chemical class COP(O)=O QCMYYKRYFNMIEC-UHFFFAOYSA-N 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 241000588921 Enterobacteriaceae Species 0.000 description 2
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 2
- 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 2
- 235000010469 Glycine max Nutrition 0.000 description 2
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 2
- 108091092195 Intron Proteins 0.000 description 2
- 241000588748 Klebsiella Species 0.000 description 2
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- SHZGCJCMOBCMKK-JFNONXLTSA-N L-rhamnopyranose Chemical compound C[C@@H]1OC(O)[C@H](O)[C@H](O)[C@H]1O SHZGCJCMOBCMKK-JFNONXLTSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- 108010006519 Molecular Chaperones Proteins 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 108700026244 Open Reading Frames Proteins 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 108700008625 Reporter Genes Proteins 0.000 description 2
- 108091028664 Ribonucleotide Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 244000061456 Solanum tuberosum Species 0.000 description 2
- 235000002595 Solanum tuberosum Nutrition 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 241000209140 Triticum Species 0.000 description 2
- 235000021307 Triticum Nutrition 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 2
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- PNNNRSAQSRJVSB-BXKVDMCESA-N aldehydo-L-rhamnose Chemical compound C[C@H](O)[C@H](O)[C@@H](O)[C@@H](O)C=O PNNNRSAQSRJVSB-BXKVDMCESA-N 0.000 description 2
- 125000003302 alkenyloxy group Chemical group 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 2
- 125000005129 aryl carbonyl group Chemical group 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 230000036983 biotransformation Effects 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- FPPNZSSZRUTDAP-UWFZAAFLSA-N carbenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C(C(O)=O)C1=CC=CC=C1 FPPNZSSZRUTDAP-UWFZAAFLSA-N 0.000 description 2
- 229960003669 carbenicillin Drugs 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- CRQQGFGUEAVUIL-UHFFFAOYSA-N chlorothalonil Chemical compound ClC1=C(Cl)C(C#N)=C(Cl)C(C#N)=C1Cl CRQQGFGUEAVUIL-UHFFFAOYSA-N 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000005090 green fluorescent protein Substances 0.000 description 2
- 235000014304 histidine Nutrition 0.000 description 2
- 238000002744 homologous recombination Methods 0.000 description 2
- 230000006801 homologous recombination Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000006252 n-propylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C(*)=O 0.000 description 2
- 238000007857 nested PCR Methods 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 125000006574 non-aromatic ring group Chemical group 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- 238000010647 peptide synthesis reaction Methods 0.000 description 2
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 230000001323 posttranslational effect Effects 0.000 description 2
- 229960002429 proline Drugs 0.000 description 2
- 235000013930 proline Nutrition 0.000 description 2
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000010188 recombinant method Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 239000002336 ribonucleotide Substances 0.000 description 2
- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 description 2
- 229960001225 rifampicin Drugs 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000002689 soil Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 125000003107 substituted aryl group Chemical group 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 230000005030 transcription termination Effects 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- RWOLDZZTBNYTMS-SSDOTTSWSA-N (2r)-2-(2-chlorophenyl)-2-hydroxyacetic acid Chemical compound OC(=O)[C@H](O)C1=CC=CC=C1Cl RWOLDZZTBNYTMS-SSDOTTSWSA-N 0.000 description 1
- ZECLJEYAWRQVIB-QMMMGPOBSA-N (2r)-2-(2-chlorophenyl)-2-hydroxyacetonitrile Chemical compound N#C[C@H](O)C1=CC=CC=C1Cl ZECLJEYAWRQVIB-QMMMGPOBSA-N 0.000 description 1
- LSDSHEPNJSMUTI-QMMMGPOBSA-N (2r)-2-(4-chlorophenyl)-2-hydroxyacetonitrile Chemical compound N#C[C@H](O)C1=CC=C(Cl)C=C1 LSDSHEPNJSMUTI-QMMMGPOBSA-N 0.000 description 1
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
- ZWKNLRXFUTWSOY-QPJJXVBHSA-N (e)-3-phenylprop-2-enenitrile Chemical compound N#C\C=C\C1=CC=CC=C1 ZWKNLRXFUTWSOY-QPJJXVBHSA-N 0.000 description 1
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
- 125000006079 1,1,2-trimethyl-2-propenyl group Chemical group 0.000 description 1
- 125000004884 1,1,2-trimethylpropylcarbonyl group Chemical group CC(C(C)C)(C(=O)*)C 0.000 description 1
- 125000006059 1,1-dimethyl-2-butenyl group Chemical group 0.000 description 1
- 125000006033 1,1-dimethyl-2-propenyl group Chemical group 0.000 description 1
- 125000006060 1,1-dimethyl-3-butenyl group Chemical group 0.000 description 1
- 125000004866 1,1-dimethylethylcarbonyl group Chemical group CC(C)(C(=O)*)C 0.000 description 1
- 125000004867 1,1-dimethylpropylcarbonyl group Chemical group CC(CC)(C(=O)*)C 0.000 description 1
- 125000005919 1,2,2-trimethylpropyl group Chemical group 0.000 description 1
- 125000004885 1,2,2-trimethylpropylcarbonyl group Chemical group CC(C(C)(C)C)C(=O)* 0.000 description 1
- 125000006061 1,2-dimethyl-1-butenyl group Chemical group 0.000 description 1
- 125000006034 1,2-dimethyl-1-propenyl group Chemical group 0.000 description 1
- 125000006062 1,2-dimethyl-2-butenyl group Chemical group 0.000 description 1
- 125000006035 1,2-dimethyl-2-propenyl group Chemical group 0.000 description 1
- 125000006063 1,2-dimethyl-3-butenyl group Chemical group 0.000 description 1
- 125000005918 1,2-dimethylbutyl group Chemical group 0.000 description 1
- 125000004877 1,2-dimethylbutylcarbonyl group Chemical group CC(C(CC)C)C(=O)* 0.000 description 1
- 125000004868 1,2-dimethylpropylcarbonyl group Chemical group CC(C(C)C)C(=O)* 0.000 description 1
- 125000006064 1,3-dimethyl-1-butenyl group Chemical group 0.000 description 1
- 125000006065 1,3-dimethyl-2-butenyl group Chemical group 0.000 description 1
- 125000006066 1,3-dimethyl-3-butenyl group Chemical group 0.000 description 1
- 125000004878 1,3-dimethylbutylcarbonyl group Chemical group CC(CC(C)C)C(=O)* 0.000 description 1
- NHOCTWDPXHCESY-UHFFFAOYSA-N 1,4-dihydroimidazol-5-one;sulfonylurea Chemical class O=C1CNC=N1.NC(=O)N=S(=O)=O NHOCTWDPXHCESY-UHFFFAOYSA-N 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000006073 1-ethyl-1-butenyl group Chemical group 0.000 description 1
- 125000006080 1-ethyl-1-methyl-2-propenyl group Chemical group 0.000 description 1
- 125000004886 1-ethyl-1-methylpropylcarbonyl group Chemical group C(C)C(CC)(C(=O)*)C 0.000 description 1
- 125000006036 1-ethyl-1-propenyl group Chemical group 0.000 description 1
- 125000006074 1-ethyl-2-butenyl group Chemical group 0.000 description 1
- 125000006081 1-ethyl-2-methyl-1-propenyl group Chemical group 0.000 description 1
- 125000006082 1-ethyl-2-methyl-2-propenyl group Chemical group 0.000 description 1
- 125000004887 1-ethyl-2-methylpropylcarbonyl group Chemical group C(C)C(C(C)C)C(=O)* 0.000 description 1
- 125000006037 1-ethyl-2-propenyl group Chemical group 0.000 description 1
- 125000006075 1-ethyl-3-butenyl group Chemical group 0.000 description 1
- 125000006218 1-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004882 1-ethylbutylcarbonyl group Chemical group C(C)C(CCC)C(=O)* 0.000 description 1
- 125000004870 1-ethylpropylcarbonyl group Chemical group C(C)C(CC)C(=O)* 0.000 description 1
- 125000006039 1-hexenyl group Chemical group 0.000 description 1
- 125000006025 1-methyl-1-butenyl group Chemical group 0.000 description 1
- 125000006044 1-methyl-1-pentenyl group Chemical group 0.000 description 1
- 125000006028 1-methyl-2-butenyl group Chemical group 0.000 description 1
- 125000006030 1-methyl-3-butenyl group Chemical group 0.000 description 1
- 125000006052 1-methyl-3-pentenyl group Chemical group 0.000 description 1
- FEFNLMIFMCISIM-UHFFFAOYSA-N 1-methyl-4-nitro-5-(4-nitrophenyl)sulfanylimidazole Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=CC=C([N+]([O-])=O)C=C1 FEFNLMIFMCISIM-UHFFFAOYSA-N 0.000 description 1
- 125000006055 1-methyl-4-pentenyl group Chemical group 0.000 description 1
- 125000004679 1-methylbutylcarbonyl group Chemical group CC(CCC)C(=O)* 0.000 description 1
- 125000004677 1-methylethylcarbonyl group Chemical group CC(C)C(=O)* 0.000 description 1
- 125000004872 1-methylpentylcarbonyl group Chemical group CC(CCCC)C(=O)* 0.000 description 1
- 125000004678 1-methylpropylcarbonyl group Chemical group CC(CC)C(=O)* 0.000 description 1
- 125000006023 1-pentenyl group Chemical group 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
- VGONTNSXDCQUGY-RRKCRQDMSA-N 2'-deoxyinosine Chemical group C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC2=O)=C2N=C1 VGONTNSXDCQUGY-RRKCRQDMSA-N 0.000 description 1
- 125000006067 2,2-dimethyl-3-butenyl group Chemical group 0.000 description 1
- 125000004879 2,2-dimethylbutylcarbonyl group Chemical group CC(CC(=O)*)(CC)C 0.000 description 1
- 125000004869 2,2-dimethylpropylcarbonyl group Chemical group CC(CC(=O)*)(C)C 0.000 description 1
- VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 1
- 125000006068 2,3-dimethyl-1-butenyl group Chemical group 0.000 description 1
- 125000006069 2,3-dimethyl-2-butenyl group Chemical group 0.000 description 1
- 125000006070 2,3-dimethyl-3-butenyl group Chemical group 0.000 description 1
- 125000004880 2,3-dimethylbutylcarbonyl group Chemical group CC(CC(=O)*)C(C)C 0.000 description 1
- RWOLDZZTBNYTMS-UHFFFAOYSA-N 2-(2-chlorophenyl)-2-hydroxyacetic acid Chemical compound OC(=O)C(O)C1=CC=CC=C1Cl RWOLDZZTBNYTMS-UHFFFAOYSA-N 0.000 description 1
- XOMXWBCHMZFRQX-UHFFFAOYSA-N 2-(2-chlorophenyl)propanenitrile Chemical compound N#CC(C)C1=CC=CC=C1Cl XOMXWBCHMZFRQX-UHFFFAOYSA-N 0.000 description 1
- ILGVZPUAKAKBDA-UHFFFAOYSA-N 2-(2-hydroxyphenyl)propanenitrile Chemical compound N#CC(C)C1=CC=CC=C1O ILGVZPUAKAKBDA-UHFFFAOYSA-N 0.000 description 1
- WTLNOANVTIKPEE-UHFFFAOYSA-N 2-acetyloxypropanoic acid Chemical class OC(=O)C(C)OC(C)=O WTLNOANVTIKPEE-UHFFFAOYSA-N 0.000 description 1
- JTIHSSVKTWPPHI-UHFFFAOYSA-N 2-amino-2-phenylacetonitrile Chemical compound N#CC(N)C1=CC=CC=C1 JTIHSSVKTWPPHI-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- VBUYCZFBVCCYFD-YVZJFKFKSA-N 2-dehydro-L-gluconic acid Chemical compound OC[C@H](O)[C@H](O)[C@@H](O)C(=O)C(O)=O VBUYCZFBVCCYFD-YVZJFKFKSA-N 0.000 description 1
- MBPFNOMGYSRGQZ-PBXRRBTRSA-N 2-deoxy-D-glucose 6-phosphate Chemical compound OP(=O)(O)OC[C@@H](O)[C@@H](O)[C@H](O)CC=O MBPFNOMGYSRGQZ-PBXRRBTRSA-N 0.000 description 1
- 125000006076 2-ethyl-1-butenyl group Chemical group 0.000 description 1
- 125000006077 2-ethyl-2-butenyl group Chemical group 0.000 description 1
- 125000006078 2-ethyl-3-butenyl group Chemical group 0.000 description 1
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004883 2-ethylbutylcarbonyl group Chemical group C(C)C(CC(=O)*)CC 0.000 description 1
- 125000006040 2-hexenyl group Chemical group 0.000 description 1
- ONFOSYPQQXJWGS-UHFFFAOYSA-N 2-hydroxy-4-(methylthio)butanoic acid Chemical compound CSCCC(O)C(O)=O ONFOSYPQQXJWGS-UHFFFAOYSA-N 0.000 description 1
- VWWOJJANXYSACS-UHFFFAOYSA-N 2-hydroxy-4-methylsulfanylbutanenitrile Chemical compound CSCCC(O)C#N VWWOJJANXYSACS-UHFFFAOYSA-N 0.000 description 1
- CUJUQPVHWIDESZ-UHFFFAOYSA-N 2-hydroxy-4-phenylbutanenitrile Chemical compound N#CC(O)CCC1=CC=CC=C1 CUJUQPVHWIDESZ-UHFFFAOYSA-N 0.000 description 1
- 125000006026 2-methyl-1-butenyl group Chemical group 0.000 description 1
- 125000006045 2-methyl-1-pentenyl group Chemical group 0.000 description 1
- 125000006029 2-methyl-2-butenyl group Chemical group 0.000 description 1
- 125000006049 2-methyl-2-pentenyl group Chemical group 0.000 description 1
- 125000006031 2-methyl-3-butenyl group Chemical group 0.000 description 1
- 125000006053 2-methyl-3-pentenyl group Chemical group 0.000 description 1
- 125000006056 2-methyl-4-pentenyl group Chemical group 0.000 description 1
- MHNNAWXXUZQSNM-UHFFFAOYSA-N 2-methylbut-1-ene Chemical compound CCC(C)=C MHNNAWXXUZQSNM-UHFFFAOYSA-N 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- 125000004680 2-methylbutylcarbonyl group Chemical group CC(CC(=O)*)CC 0.000 description 1
- 125000005916 2-methylpentyl group Chemical group 0.000 description 1
- 125000004873 2-methylpentylcarbonyl group Chemical group CC(CC(=O)*)CCC 0.000 description 1
- 125000006024 2-pentenyl group Chemical group 0.000 description 1
- NVAOLENBKNECGF-UHFFFAOYSA-N 2-phenylpropanenitrile Chemical compound N#CC(C)C1=CC=CC=C1 NVAOLENBKNECGF-UHFFFAOYSA-N 0.000 description 1
- GWZCLMWEJWPFFA-UHFFFAOYSA-N 2-thiophen-3-ylacetonitrile Chemical compound N#CCC=1C=CSC=1 GWZCLMWEJWPFFA-UHFFFAOYSA-N 0.000 description 1
- 125000006071 3,3-dimethyl-1-butenyl group Chemical group 0.000 description 1
- 125000006072 3,3-dimethyl-2-butenyl group Chemical group 0.000 description 1
- 125000004881 3,3-dimethylbutylcarbonyl group Chemical group CC(CCC(=O)*)(C)C 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- 125000006041 3-hexenyl group Chemical group 0.000 description 1
- 125000006027 3-methyl-1-butenyl group Chemical group 0.000 description 1
- 125000006046 3-methyl-1-pentenyl group Chemical group 0.000 description 1
- 125000006050 3-methyl-2-pentenyl group Chemical group 0.000 description 1
- 125000006032 3-methyl-3-butenyl group Chemical group 0.000 description 1
- 125000006054 3-methyl-3-pentenyl group Chemical group 0.000 description 1
- 125000006057 3-methyl-4-pentenyl group Chemical group 0.000 description 1
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000004681 3-methylbutylcarbonyl group Chemical group CC(CCC(=O)*)C 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- 125000004874 3-methylpentylcarbonyl group Chemical group CC(CCC(=O)*)CC 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 125000006042 4-hexenyl group Chemical group 0.000 description 1
- 125000006047 4-methyl-1-pentenyl group Chemical group 0.000 description 1
- 125000006051 4-methyl-2-pentenyl group Chemical group 0.000 description 1
- 125000003119 4-methyl-3-pentenyl group Chemical group [H]\C(=C(/C([H])([H])[H])C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000006058 4-methyl-4-pentenyl group Chemical group 0.000 description 1
- 125000004875 4-methylpentylcarbonyl group Chemical group CC(CCCC(=O)*)C 0.000 description 1
- UHPMCKVQTMMPCG-UHFFFAOYSA-N 5,8-dihydroxy-2-methoxy-6-methyl-7-(2-oxopropyl)naphthalene-1,4-dione Chemical compound CC1=C(CC(C)=O)C(O)=C2C(=O)C(OC)=CC(=O)C2=C1O UHPMCKVQTMMPCG-UHFFFAOYSA-N 0.000 description 1
- 125000006043 5-hexenyl group Chemical group 0.000 description 1
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
- 230000005730 ADP ribosylation Effects 0.000 description 1
- 241000589220 Acetobacter Species 0.000 description 1
- 108010000700 Acetolactate synthase Proteins 0.000 description 1
- 241000726118 Acidovorax facilis Species 0.000 description 1
- 241000589291 Acinetobacter Species 0.000 description 1
- 241000203809 Actinomycetales Species 0.000 description 1
- 241000589156 Agrobacterium rhizogenes Species 0.000 description 1
- 241000589155 Agrobacterium tumefaciens Species 0.000 description 1
- 108010025188 Alcohol oxidase Proteins 0.000 description 1
- 108010029598 Aliphatic nitrilase Proteins 0.000 description 1
- 108700028369 Alleles Proteins 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
- 244000105975 Antidesma platyphyllum Species 0.000 description 1
- 241000219195 Arabidopsis thaliana Species 0.000 description 1
- 101000997104 Arabidopsis thaliana Nitrilase 1 Proteins 0.000 description 1
- 241000186063 Arthrobacter Species 0.000 description 1
- 241000186073 Arthrobacter sp. Species 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 101000755953 Bacillus subtilis (strain 168) Ribosome maturation factor RimP Proteins 0.000 description 1
- 208000035143 Bacterial infection Diseases 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
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 235000014698 Brassica juncea var multisecta Nutrition 0.000 description 1
- 235000006008 Brassica napus var napus Nutrition 0.000 description 1
- 235000006618 Brassica rapa subsp oleifera Nutrition 0.000 description 1
- 244000188595 Brassica sinapistrum Species 0.000 description 1
- 235000004977 Brassica sinapistrum Nutrition 0.000 description 1
- 241001453380 Burkholderia Species 0.000 description 1
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 1
- 241000588923 Citrobacter Species 0.000 description 1
- 241000193403 Clostridium Species 0.000 description 1
- 241001478312 Comamonas sp. Species 0.000 description 1
- 241000589518 Comamonas testosteroni Species 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 241000186249 Corynebacterium sp. Species 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 108030005368 Cyanoalanine nitrilases Proteins 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
- XPYBSIWDXQFNMH-UHFFFAOYSA-N D-fructose 1,6-bisphosphate Natural products OP(=O)(O)OCC(O)C(O)C(O)C(=O)COP(O)(O)=O XPYBSIWDXQFNMH-UHFFFAOYSA-N 0.000 description 1
- 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 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- ZAQJHHRNXZUBTE-NQXXGFSBSA-N D-ribulose Chemical compound OC[C@@H](O)[C@@H](O)C(=O)CO ZAQJHHRNXZUBTE-NQXXGFSBSA-N 0.000 description 1
- ZAQJHHRNXZUBTE-UHFFFAOYSA-N D-threo-2-Pentulose Natural products OCC(O)C(O)C(=O)CO ZAQJHHRNXZUBTE-UHFFFAOYSA-N 0.000 description 1
- 102100027887 Deaminated glutathione amidase Human genes 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 241000588914 Enterobacter Species 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 108091092566 Extrachromosomal DNA Proteins 0.000 description 1
- 108010014173 Factor X Proteins 0.000 description 1
- 241000579497 Falsibacillus pallidus Species 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 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 1
- 239000005715 Fructose Substances 0.000 description 1
- 241000223218 Fusarium Species 0.000 description 1
- 241000223221 Fusarium oxysporum Species 0.000 description 1
- 241000427940 Fusarium solani Species 0.000 description 1
- 108700007698 Genetic Terminator Regions Proteins 0.000 description 1
- 241000589236 Gluconobacter Species 0.000 description 1
- 108010068370 Glutens Proteins 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 239000005562 Glyphosate Substances 0.000 description 1
- 241000219146 Gossypium Species 0.000 description 1
- 101150009006 HIS3 gene Proteins 0.000 description 1
- 101000632167 Homo sapiens Deaminated glutathione amidase Proteins 0.000 description 1
- 101000582320 Homo sapiens Neurogenic differentiation factor 6 Proteins 0.000 description 1
- 101000996087 Homo sapiens Omega-amidase NIT2 Proteins 0.000 description 1
- 240000005979 Hordeum vulgare Species 0.000 description 1
- 235000007340 Hordeum vulgare Nutrition 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-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
- 102000004195 Isomerases Human genes 0.000 description 1
- 108090000769 Isomerases Proteins 0.000 description 1
- 241000588744 Klebsiella pneumoniae subsp. ozaenae Species 0.000 description 1
- 241000235649 Kluyveromyces Species 0.000 description 1
- LKDRXBCSQODPBY-AMVSKUEXSA-N L-(-)-Sorbose Chemical compound OCC1(O)OC[C@H](O)[C@@H](O)[C@@H]1O LKDRXBCSQODPBY-AMVSKUEXSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
- QEFRNWWLZKMPFJ-ZXPFJRLXSA-N L-methionine (R)-S-oxide Chemical compound C[S@@](=O)CC[C@H]([NH3+])C([O-])=O QEFRNWWLZKMPFJ-ZXPFJRLXSA-N 0.000 description 1
- QEFRNWWLZKMPFJ-UHFFFAOYSA-N L-methionine sulphoxide Natural products CS(=O)CCC(N)C(O)=O QEFRNWWLZKMPFJ-UHFFFAOYSA-N 0.000 description 1
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-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
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 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
- 101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001555627 Melonis Species 0.000 description 1
- 241001467578 Microbacterium Species 0.000 description 1
- 102000005431 Molecular Chaperones Human genes 0.000 description 1
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- 102100030589 Neurogenic differentiation factor 6 Human genes 0.000 description 1
- 101000996085 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) Nitrogen catabolic enzyme regulatory protein Proteins 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- 108091092724 Noncoding DNA Proteins 0.000 description 1
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102100034446 Omega-amidase NIT2 Human genes 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001631646 Papillomaviridae Species 0.000 description 1
- 241000228143 Penicillium Species 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- 108010002747 Pfu DNA polymerase Proteins 0.000 description 1
- 101710163504 Phaseolin Proteins 0.000 description 1
- DYUQAZSOFZSPHD-UHFFFAOYSA-N Phenylpropanol Chemical compound CCC(O)C1=CC=CC=C1 DYUQAZSOFZSPHD-UHFFFAOYSA-N 0.000 description 1
- IAJOBQBIJHVGMQ-UHFFFAOYSA-N Phosphinothricin Natural products CP(O)(=O)CCC(N)C(O)=O IAJOBQBIJHVGMQ-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241001505332 Polyomavirus sp. Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 108010011939 Pyruvate Decarboxylase Proteins 0.000 description 1
- MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 description 1
- 235000019484 Rapeseed oil Nutrition 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 241000187562 Rhodococcus sp. Species 0.000 description 1
- 241000190932 Rhodopseudomonas Species 0.000 description 1
- 101100394989 Rhodopseudomonas palustris (strain ATCC BAA-98 / CGA009) hisI gene Proteins 0.000 description 1
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 108030005366 Ricinine nitrilases Proteins 0.000 description 1
- 229910003798 SPO2 Inorganic materials 0.000 description 1
- 241000235070 Saccharomyces Species 0.000 description 1
- 101100434411 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) ADH1 gene Proteins 0.000 description 1
- 240000000111 Saccharum officinarum Species 0.000 description 1
- 235000007201 Saccharum officinarum Nutrition 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 101100478210 Schizosaccharomyces pombe (strain 972 / ATCC 24843) spo2 gene Proteins 0.000 description 1
- 241000607720 Serratia Species 0.000 description 1
- 241000607768 Shigella Species 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 101100370749 Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145) trpC1 gene Proteins 0.000 description 1
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 1
- 206010042297 Subacute sclerosing panencephalitis Diseases 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
- 108020005038 Terminator Codon Proteins 0.000 description 1
- JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- 102000002933 Thioredoxin Human genes 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 108020004566 Transfer RNA Proteins 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 1
- 108090000848 Ubiquitin Proteins 0.000 description 1
- 102000044159 Ubiquitin Human genes 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 241001478283 Variovorax Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 241000607734 Yersinia <bacteria> Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 101150102866 adc1 gene Proteins 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- RNBGYGVWRKECFJ-ZXXMMSQZSA-N alpha-D-fructofuranose 1,6-bisphosphate Chemical compound O[C@H]1[C@H](O)[C@](O)(COP(O)(O)=O)O[C@@H]1COP(O)(O)=O RNBGYGVWRKECFJ-ZXXMMSQZSA-N 0.000 description 1
- 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 1
- 230000004075 alteration Effects 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 230000010516 arginylation Effects 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
- 238000007845 assembly PCR Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 238000010923 batch production Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 102000006635 beta-lactamase Human genes 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
- 230000002210 biocatalytic effect Effects 0.000 description 1
- 230000008827 biological function Effects 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
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001721 carbon Chemical group 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
- 238000012219 cassette mutagenesis Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000012411 cloning technique Methods 0.000 description 1
- 101150036359 clpB gene Proteins 0.000 description 1
- 230000004186 co-expression Effects 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 235000021310 complex sugar Nutrition 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 239000000287 crude extract Substances 0.000 description 1
- XLJMAIOERFSOGZ-UHFFFAOYSA-M cyanate Chemical compound [O-]C#N XLJMAIOERFSOGZ-UHFFFAOYSA-M 0.000 description 1
- 125000003493 decenyl group Chemical group [H]C([*])=C([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 125000006612 decyloxy group Chemical group 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 230000017858 demethylation Effects 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 230000012361 double-strand break repair Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000005496 eutectics Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 230000022244 formylation Effects 0.000 description 1
- 238000006170 formylation reaction Methods 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- RNBGYGVWRKECFJ-UHFFFAOYSA-N fructose-1,6-phosphate Natural products OC1C(O)C(O)(COP(O)(O)=O)OC1COP(O)(O)=O RNBGYGVWRKECFJ-UHFFFAOYSA-N 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- UHBYWPGGCSDKFX-VKHMYHEASA-N gamma-carboxy-L-glutamic acid Chemical compound OC(=O)[C@@H](N)CC(C(O)=O)C(O)=O UHBYWPGGCSDKFX-VKHMYHEASA-N 0.000 description 1
- 230000006251 gamma-carboxylation Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000009395 genetic defect Effects 0.000 description 1
- 230000004034 genetic regulation Effects 0.000 description 1
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Natural products O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 1
- IAJOBQBIJHVGMQ-BYPYZUCNSA-N glufosinate-P Chemical compound CP(O)(=O)CC[C@H](N)C(O)=O IAJOBQBIJHVGMQ-BYPYZUCNSA-N 0.000 description 1
- 125000000291 glutamic acid group Chemical class N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
- 235000021312 gluten Nutrition 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- XDDAORKBJWWYJS-UHFFFAOYSA-N glyphosate Chemical compound OC(=O)CNCP(O)(O)=O XDDAORKBJWWYJS-UHFFFAOYSA-N 0.000 description 1
- 229940097068 glyphosate Drugs 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000007952 growth promoter Substances 0.000 description 1
- 101150053330 grpE gene Proteins 0.000 description 1
- 235000009424 haa Nutrition 0.000 description 1
- 150000003278 haem Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 101150107671 hisB gene Proteins 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 238000000126 in silico method Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000002361 inverse photoelectron spectroscopy Methods 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 159000000014 iron salts Chemical class 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 101150109249 lacI gene Proteins 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 101150025049 leuB gene Proteins 0.000 description 1
- WQVJUBFKFCDYDQ-BBWFWOEESA-N leubethanol Natural products C1=C(C)C=C2[C@H]([C@H](CCC=C(C)C)C)CC[C@@H](C)C2=C1O WQVJUBFKFCDYDQ-BBWFWOEESA-N 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012092 media component Substances 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-O methylsulfide anion Chemical compound [SH2+]C LSDPWZHWYPCBBB-UHFFFAOYSA-O 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000033607 mismatch repair Effects 0.000 description 1
- 239000011733 molybdenum Substances 0.000 description 1
- 229910052750 molybdenum Inorganic materials 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 231100000219 mutagenic Toxicity 0.000 description 1
- 231100000707 mutagenic chemical Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 230000007498 myristoylation Effects 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
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000005185 naphthylcarbonyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 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
- 101150025351 nit-3 gene Proteins 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 125000002560 nitrile group Chemical group 0.000 description 1
- 238000010641 nitrile hydrolysis reaction Methods 0.000 description 1
- 229910017464 nitrogen compound Inorganic materials 0.000 description 1
- 150000002830 nitrogen compounds Chemical class 0.000 description 1
- 125000005187 nonenyl group Chemical group C(=CCCCCCCC)* 0.000 description 1
- 239000002853 nucleic acid probe Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229940014662 pantothenate Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- YWAKXRMUMFPDSH-UHFFFAOYSA-N pentene Chemical compound CCCC=C YWAKXRMUMFPDSH-UHFFFAOYSA-N 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 238000003359 percent control normalization Methods 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- LWTDZKXXJRRKDG-UHFFFAOYSA-N phaseollin Natural products C1OC2=CC(O)=CC=C2C2C1C1=CC=C3OC(C)(C)C=CC3=C1O2 LWTDZKXXJRRKDG-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003905 phosphatidylinositols Chemical class 0.000 description 1
- 108010082527 phosphinothricin N-acetyltransferase Proteins 0.000 description 1
- 150000008298 phosphoramidates Chemical class 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 1
- 230000029553 photosynthesis Effects 0.000 description 1
- 238000010672 photosynthesis Methods 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000013823 prenylation Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 201000005484 prostate carcinoma in situ Diseases 0.000 description 1
- 230000009145 protein modification Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 235000008160 pyridoxine Nutrition 0.000 description 1
- 239000011677 pyridoxine Substances 0.000 description 1
- 229940043131 pyroglutamate Drugs 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose 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[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 101150091078 rhaA gene Proteins 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 102220277134 rs776745497 Human genes 0.000 description 1
- 235000019515 salmon Nutrition 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
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 239000013605 shuttle vector Substances 0.000 description 1
- 230000037432 silent mutation Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000003549 soybean oil 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
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 230000019635 sulfation Effects 0.000 description 1
- 238000005670 sulfation reaction Methods 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 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
- 239000011721 thiamine Substances 0.000 description 1
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 description 1
- 235000019157 thiamine Nutrition 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- GSXCEVHRIVLFJV-UHFFFAOYSA-N thiophene-3-carbonitrile Chemical compound N#CC=1C=CSC=1 GSXCEVHRIVLFJV-UHFFFAOYSA-N 0.000 description 1
- 108060008226 thioredoxin Proteins 0.000 description 1
- 229940094937 thioredoxin Drugs 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 238000013024 troubleshooting Methods 0.000 description 1
- 101150016309 trpC gene Proteins 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 229960004295 valine Drugs 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 229940011671 vitamin b6 Drugs 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 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
- C12N9/14—Hydrolases (3)
- C12N9/78—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
- C12N9/80—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5) acting on amide bonds in linear amides (3.5.1)
-
- 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
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/82—Vectors or expression systems specially adapted for eukaryotic hosts for plant cells, e.g. plant artificial chromosomes (PACs)
- C12N15/8241—Phenotypically and genetically modified plants via recombinant DNA technology
- C12N15/8261—Phenotypically and genetically modified plants via recombinant DNA technology with agronomic (input) traits, e.g. crop yield
- C12N15/8271—Phenotypically and genetically modified plants via recombinant DNA technology with agronomic (input) traits, e.g. crop yield for stress resistance, e.g. heavy metal resistance
- C12N15/8274—Phenotypically and genetically modified plants via recombinant DNA technology with agronomic (input) traits, e.g. crop yield for stress resistance, e.g. heavy metal resistance for herbicide resistance
-
- 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
- C12P7/00—Preparation of oxygen-containing organic compounds
- C12P7/40—Preparation of oxygen-containing organic compounds containing a carboxyl group including Peroxycarboxylic acids
-
- 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
- C12P7/40—Preparation of oxygen-containing organic compounds containing a carboxyl group including Peroxycarboxylic acids
- C12P7/42—Hydroxy-carboxylic acids
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Microbiology (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Cell Biology (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Enzymes And Modification Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Breeding Of Plants And Reproduction By Means Of Culturing (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
a) (K/R/H)XXDXXGX(X*)、
b) i) KAINDPVGH(X*)
ii) GH(X*)SRPDV
を含む配列の群から選択されたニトリラーゼ共通配列に対して、少なくとも50%の相
同性を有する配列、
c) i) DP(A/V)GH(X*)SRPDV(L/T)(S/R)L
ii) DPAGH(X*)SRPDVLSLLV
を含む配列の群から選択されたニトリラーゼ共通配列に対して、少なくとも35%の相
同性を有する配列、
を含む配列の群から選択された、少なくとも1つの配列を含み、
前記単離されたポリペプチドに含まれる前記配列において、X*はチロシンでない1個のアミノ酸残基を表し、ここで、X*は配列番号2に記載されている野生型Alcaligenes faecalisニトリラーゼ中の296番目の位置に相当する位置に存在するものである。好ましくは、前記ニトリラーゼ共通配列との相同性が少なくとも40%、さらに好ましくは少なくとも60%または80%、最も好ましくは少なくとも90%または95%である。
a) (K/R)XXXDXXG(H/Y/S)(X*)、
b) KXXXDXXGX(X*)、
c) KAINDPVGH(X*)、
d) GH(X*)SRPDV、
e) DP(A/V)GH(X*)SRPDV(L/T)(S/R)L、
f) DPAGH(X*)SRPDVLSLLV、
よりなる群から選択された1つの配列を含み、
ここでXはあらゆるアミノ酸を表し、本発明の前記ニトリラーゼに含まれる前記配列において、X*はチロシンでない1個のアミノ酸残基を表し、X*は配列番号2に記載されている野生型Alcaligenes faecalisニトリラーゼ中の296番目の位置に相当する位置に存在するものである。好ましくは本発明のニトリラーゼは、
a) KAINDPVGH(X*)、
b) DP(A/V)GH(X*)SRPDV(L/T)(S/R)L、または、最も好ましくは、
DPAGH(X*)SRPDVLSLLV、
よりなる群から選択された1つの配列を含む。
図1:ラセミ体2-クロロマンデロニトリルの変換についての、種々のY296変異体と、対照(control)/標準としてのY296野生型との相対的比活性(RSA)の比較(実施例2参照)。Y軸は相対的比活性(RSA)を表している。比活性は、以下に記載のように測定した。相対的比活性は、野生型(Y296)酵素の活性を1.0に設定して計算した。X軸は、以下の様々な変異体を表している:A(Y296A)、F(Y296F)、C(Y296C)、G(Y296G)、N(Y296N)、T(Y296T)、S(Y296S)。テストした変異体のいずれもが、野生型Y296ニトリラーゼに比べて高い活性を示している。
a) 前記核酸配列、または
b) 前記核酸配列a)に機能しうる様に連結された遺伝的調節配列、例えばプロモーター、または
c) (a)および(b)
のいずれかが、その元来の遺伝的環境に位置していないか、組換え法により改変されている、例えば1個以上のヌクレオチド残基の置換、付加、欠失、転移または挿入などの改変がされている構築物を指す。元来の遺伝的環境とは、元の生物においての元来の染色体上遺伝子座を指すか、またはゲノムライブラリー中に存在することを指す。ゲノムライブラリーの場合には、核酸配列の元来の遺伝的環境が、少なくとも部分的には保持されているのが好ましい。該環境は、少なくとも一方の側に核酸配列をつなげており、少なくとも50bp長、好ましくは少なくとも500bp長、特に好ましくは少なくとも1000bp長、非常に好ましくは少なくとも5000bp長の配列を有している。天然に存在する発現カセット(例えば天然に存在する、プロモーターとそれに対応する遺伝子の連結)は、天然でない、合成的な「人工的」方法(例えば変異導入)により改変されれば、組換え発現カセットになる。そのような方法は既に記載されている(US 5,565,350;WO 00/15815;上記も参照のこと)。好ましくは、「組換え」という語句は、本明細書中で用いられるときには、核酸に関して、核酸がその元来の環境において隣接していなかった核酸と共有結合により連結され、隣接していることを意味する。
Gap weight: 50
Length weight: 3
Average match: 10
Average mismatch: 0。
Gap weight: 8
Length weight: 2
Average match: 2,912
Average mismatch: -2,003。
York;Hames and Higgins編, 1985, Nucleic Acids Hybridization: A Practical Approach, IRL Press at Oxford University Press, Oxford;Brown編, 1991, Essential Molecular Biology: A Practical Approach, IRL Press at Oxford University Press, Oxford。特に、本明細書中で用いられるときには、「ストリンジェントなハイブリダイゼーション条件」は、42℃、50%ホルムアミド中、5x SSPE、0.3%SDS、および200ng/ml剪断変性サケ精子DNA、およびそれと同等の条件を含む。上記の範囲および条件についての変動は、当該技術分野においては公知である。
R-CN + 2 H2O →" R-COOH + NH3
を触媒する性質を意味する。
1. fPEaf
2. hRKl.pT
3. l.CWEn..p
(大文字はニトリラーゼ間での90%かそれ以上の共通性を表し、小文字は50%かそれ以上の共通性を表している。配列中のピリオドは保存されていない残基を表している。好ましくは、以下の残基(下線が引かれているもの)は同定されたニトリラーゼ全ての間で完全に保存されている:最初のモチーフもしくは領域の3番目のアミノ酸(E、グルタミン酸);2番目のモチーフの2番目の残基(R、アルギニン);2番目のモチーフの3番目の残基(K、リジン);3番目のモチーフの3番目の残基(C、システイン);および3番目のモチーフの5番目の残基(E、グルタミン酸)。
a) (K/R/H)XXDXXGX(X*)、
b) i) KAINDPVGH(X*)
ii) GH(X*)SRPDV
を含む配列の群から選択されたニトリラーゼ共通配列に対して、少なくとも50%、好
ましくは少なくとも60%、さらに好ましくは少なくとも70%または80%、最も好ま
しくは少なくとも90%または95%の相同性を有する配列、
c) i) DP(A/V)GH(X*)SRPDV(L/T)(S/R)L
ii) DPAGH(X*)SRPDVLSLLV
を含む配列の群から選択されたニトリラーゼ共通配列に対して、少なくとも35%、好
ましくは少なくとも40%、さらに好ましくは少なくとも60%または80%、最も好ま
しくは少なくとも90%または95%の相同性を有する配列、
を含む配列の群から選択された、少なくとも1つの配列を含み、
前記ニトリラーゼ活性を有する酵素に含まれる前記配列において、X*はチロシンでない1個のアミノ酸残基を表し、X*は配列番号2に記載されている野生型Alcaligenes faecalisニトリラーゼ中の296番目の位置に相当する位置に存在するものである。
a) (K/R)XXXDXXG(H/Y/S)(X*)、
b) KXXXDXXGX(X*)、
c) KAINDPVGH(X*)、
d) GH(X*)SRPDV、
e) DP(A/V)GH(X*)SRPDV(L/T)(S/R)L、
f) DPAGH(X*)SRPDVLSLLV、
よりなる群から選択された1つの配列を含み、
ここでXはあらゆるアミノ酸を表し、本発明の前記ニトリラーゼに含まれる前記配列において、X*はチロシンでない1個のアミノ酸残基を表し、X*は配列番号2に記載されている野生型Alcaligenes faecalisニトリラーゼ中の296番目の位置に相当する位置に存在するものである。好ましくは本発明のニトリラーゼは、
a) KAINDPVGH(X*)、
b) DP(A/V)GH(X*)SRPDV(L/T)(S/R)L、または、最も好ましくは、
DPAGH(X*)SRPDVLSLLV、
よりなる群から選択された1つの配列を含む。
a) 配列番号2、4、6、または8のアミノ酸配列と少なくとも60%、好ましくは80%、
さらに好ましくは90%、最も好ましくは95%同一であるアミノ酸配列を含むポリペプ
チド分子;
b) 配列番号2、4、6、または8に記載された配列のうち、少なくとも1つの、少なく
とも20の連続したアミノ酸、好ましくは50の連続したアミノ酸の断片を含むポリペ
プチド分子、
よりなる群から選択された1つのポリペプチド配列により表されることを特徴とする。
a) (K/R/H)XXDXXGX(X*)、
b) i) KAINDPVGH(X*)
ii) GH(X*)SRPDV
を含む配列の群から選択されたニトリラーゼ共通配列に対して、少なくとも50%、好
ましくは少なくとも60%、さらに好ましくは少なくとも70%または80%、最も好ま
しくは少なくとも90%または95%の相同性を有する配列、
c) i) DP(A/V)GH(X*)SRPDV(L/T)(S/R)L
ii) DPAGH(X*)SRPDVLSLLV
を含む配列の群から選択されたニトリラーゼ共通配列に対して、少なくとも35%、好
ましくは少なくとも40%、さらに好ましくは少なくとも60%または80%、最も好ま
しくは少なくとも90%または95%の相同性を有する配列、
を含む配列の群から選択された、少なくとも1つの配列を含み、
前記ニトリラーゼ活性を有する酵素に含まれる前記配列において、X*はチロシンでない1個のアミノ酸残基を表し、X*は配列番号2に記載されている野生型Alcaligenes faecalisニトリラーゼ中の296番目の位置に相当する位置に存在するものである。
a) (K/R)XXXDXXG(H/Y/S)(X*)、
b) KXXXDXXGX(X*)、
c) KAINDPVGH(X*)、
d) GH(X*)SRPDV、
e) DP(A/V)GH(X*)SRPDV(L/T)(S/R)L、
f) DPAGH(X*)SRPDVLSLLV、
よりなる群から選択された1つの配列を含むニトリラーゼをコードし、
ここでXはあらゆるアミノ酸を表し、本発明の前記ニトリラーゼに含まれる前記配列において、X*はチロシンでない1個のアミノ酸残基を表し、X*は配列番号2に記載されている野生型Alcaligenes faecalisニトリラーゼ中の296番目の位置に相当する位置に存在するものである。
a) KAINDPVGH(X*)、
b) DP(A/V)GH(X*)SRPDV(L/T)(S/R)L、または、最も好ましくは、
DPAGH(X*)SRPDVLSLLV、
よりなる群から選択された1つの配列を含む、ニトリラーゼ活性を有する酵素をコードしている。
a) 配列番号1、3、5、または7の核酸配列と少なくとも60%、好ましくは80%、
さらに好ましくは90%、最も好ましくは95%同一である核酸配列;
b) 配列番号1、3、5、または7に記載された配列のうち、少なくとも1つの、少なく
とも20の連続した塩基、好ましくは50の連続した塩基、さらに好ましくは100の連
続した塩基の、少なくとも1つの断片を含む核酸配列、
よりなる群から選択された1つの配列により表されることを特徴とする。
a) 選択マーカー
選択マーカーは、形質転換または相同組換えに成功した細胞を選別し、分離するのに有用であり、時間が経つ間に染色体外のDNA構築物が失われるのを防ぐのに有用である。選択マーカーは、代謝阻害剤(例えば2-デオキシグルコース-6-リン酸、WO 98/45456)、抗生物質(例えば、アンピシリン、テトラサイクリン、カナマイシン、G 418、ブレオマイシンまたはハイグロマイシン)または除草剤(例えば、ホスフィノトリシンまたはグリホサート)のような殺生性化合物に対する耐性を与える。
R1、R2、R3は互いに独立に、水素、置換または非置換の、分岐または非分岐のC1-C10-アルキルまたはC1-C10-アルコキシ、置換または非置換のアリールまたはヘテロアリール、ヒドロキシル、ハロゲン(例えばフッ素、塩素または臭素)、C1-C10-アルキルアミノおよびアミノよりなる群から選択されてもよく、置換基R1、R2およびR3のうち、少なくとも2つ、好ましくは全てが異なっている。
n=0または1
m=0、1、2または3、ここでm>2のとき、2つの隣接する炭素原子間には二重結合が
1つ存在するか、存在せず、
p=0または1
A、B、DおよびEは互いに独立にCH、NまたはCR7
H=O、S、NR4、CHまたはCR7(n=0のとき)、またはCH、NまたはCR7(n=1のとき)、
ここで、2つの隣接する可変部A、B、D、EまたはHは、他の置換または非置換芳香族、飽和または部分飽和環であって、環中に5〜8個の原子を有し、O、NまたはSのような1つ以上のヘテロ原子を含み、可変部A、B、D、EまたはHのうち3つ以上がヘテロ原子でないような環を共同して形成することが可能であり、
R4は、水素、置換または非置換の、分岐または非分岐のC1-C10-アルキルよりなる群から選択され、
R5、R6、R7は独立に、水素、置換または非置換の、分岐または非分岐のC1-C10-アルキルまたはC1-C10-アルコキシ、置換または非置換のアリールまたはヘテロアリール、ヒドロキシル、ハロゲン(例えばフッ素、塩素または臭素)、C1-C10-アルキルアミノまたはアミノよりなる群から選択されてもよい。
ブテニルカルボニル、2,3-ジメチル-1-ブテニルカルボニル、2,3-ジメチル-2-ブテニルカルボニル、2,3-ジメチル-3-ブテニルカルボニル、3,3-ジメチル-1-ブテニルカルボニル、3,3-ジメチル-2-ブテニルカルボニル、1-エチル-1-ブテニルカルボニル、1-エチル-2-ブテニルカルボニル、1-エチル-3-ブテニルカルボニル、2-エチル-1-ブテニルカルボニル、2-エチル-2-ブテニルカルボニル、2-エチル-3-ブテニルカルボニル、1,1,2-トリメチル-2-プロペニルカルボニル、1-エチル-1-メチル-2-プロペニルカルボニル、1-エチル-2-メチル-1-プロペニルカルボニル、1-エチル-2-メチル-2-プロペニルカルボニル、1-ヘプテニルカルボニル、2-ヘプテニルカルボニル、3-ヘプテニルカルボニル、4-ヘプテニルカルボニル、5-ヘプテニルカルボニル、6-ヘプテニルカルボニル、1-オクテニルカルボニル、2-オクテニルカルボニル、3-オクテニルカルボニル、4-オクテニルカルボニル、5-オクテニルカルボニル、6-オクテニルカルボニル、7-オクテニルカルボニル、ノネニルカルボニルまたはデセニルカルボニル。エテニルカルボニル、プロペニルカルボニル、ブテニルカルボニルまたはペンテニルカルボニルが好ましい。
配列番号1 Alcaligenes faecalis種に由来するニトリラーゼをコードする核酸配列
(DE19848129-A1)
配列番号2 Alcaligenes faecalis種に由来するニトリラーゼをコードするアミノ酸配列
(DE19848129-A1)
配列番号3 Alcaligenes faecalis種に由来するニトリラーゼをコードする核酸配列
(WO 99/64607)
配列番号4 Alcaligenes faecalis種に由来するニトリラーゼをコードするアミノ酸配列
(WO 99/64607)
配列番号5 Pseudomonas種に由来するニトリラーゼをコードする核酸配列
配列番号6 Pseudomonas種に由来するニトリラーゼをコードするアミノ酸配列
配列番号7 Rhodococcus rhodochrousに由来するニトリラーゼをコードする核酸配列
(DE10010149)
配列番号8 Rhodococcus rhodochrousに由来するニトリラーゼをコードするアミノ酸配
列(DE10010149)
配列番号2に記載されている野生型Alcaligenes faecalisニトリラーゼ中の296番目の位置のチロシンの置換は、重複伸長PCR(overlap-extension PCR)を用いた部位特異的突然変異誘発により実現した。以下のアプローチをとった:
実施例1に記載のように作製したプラスミドを、大腸菌TG1にトランスフォームし、100μg/mlのアンピシリンを含むLB固形培地上で平板培養した。得られたクローンを0.2mlの液体LB-Amp培地に移し、37℃で一晩生育した。この培養物の一部を、発現を誘導するために2g/lのL-ラムノースを含んだ0.2mlの液体LB-Amp培地に接種するのに用いた。培養物を一晩生育させ、回収し、2-クロロマンデロニトリルに対するそれらの酵素活性を解析した。このために、90μlの細胞懸濁液(10mM Pipes、pH7.2中)を85μlの10mM Pipes、pH7.2および25μlの2-クロロマンデロニトリル(2-CMN)(48mM、メタノール中)に添加した。50℃にて40分間インキュベートした後、HClを加えることで反応を停止した。上清を、2-クロロマンデル酸について、HPLCを用いて解析した。最大活性を有するクローンを単離し、そこからプラスミドDNAを調製し、配列決定を行い、pAgro、pHSG575を含むTG10にトランスフォームした(大腸菌TG10は、大腸菌TG1の派生型であり、ラムノースイソメラーゼrhaAの欠損を含む;pAgro(pBB541;Toshifumi Tomoyasuら(2001) Mol Microbiol 40(2):397-413)およびpHSG575(Takeshita Sら(1987) Gene 61:63-74)は、シャペロンGroELSの共発現のためのプラスミドである)。
配列番号2に記載されたニトリラーゼ(pDHE1650)およびそのY296C変異体についての発現カセットを含むpDHEベクター(上記のように作製)で形質転換された大腸菌TG10の前培養は、アンピシリン(100μg/ml)、スペクチノマイシン(50μg/ml)、クロラムフェニコール(10μg/ml)を含む25mlの液体LB培地中で、継続的な振盪(200rpm)の下、37℃にて23時間生育した。結果として得られた培養物の10mlを、アンピシリン(100μg/ml)、スペクチノマイシン(50μg/ml)、クロラムフェニコール(10μg/ml)、0.1mM IPTG、および0.5g/l ラムノースを含む400mLのLB培地に接種するのに用い、継続的な振盪(200rpm)の下、37℃にて18時間生育した。生じた生物集団を回収し、10mM Tris/HCl、pH7.0を用いて洗浄した。
4.1 Alcaligenes faecalis ATCC8750に由来するニトリラーゼ(配列番号4、「Nit8750_ALCFA」と呼ぶ)のチロシンY296のアラニンとの置換は、重複伸長PCR(overlap-extension PCR)を用いた部位特異的突然変異誘発により実現した。以下のアプローチをとった:
配列番号4に記載されたニトリラーゼおよびそのY296A変異体、配列番号6に記載されたニトリラーゼおよびそのY297A変異体についての発現カセットをそれぞれ含むpDHEベクター(上記のように作製)で形質転換された大腸菌TG10の個々の前培養は、アンピシリン(100μg/ml)、スペクチノマイシン(50μg/ml)、クロラムフェニコール(10μg/ml)を含む25mlの液体LB培地中で、継続的な振盪(200rpm)の下、37℃にて23時間生育した。結果として得られた培養物のそれぞれ10mlを、アンピシリン(100μg/ml)、スペクチノマイシン(50μg/ml)、クロラムフェニコール(10μg/ml)、0.1mM IPTG、および0.5g/L ラムノースを含む400mLのLB培地のそれぞれのバッチに接種するのに用い、継続的な振盪(200rpm)の下、37℃にて18時間生育した。生じた生物集団を別々に回収し、10mM Tris/HCl、pH7.0を用いて洗浄した。
Claims (16)
- ニトリラーゼをコードする単離されたポリペプチドであって、該ポリペプチドが配列番号2、4、6または8のアミノ酸配列に対して少なくとも90%同一なアミノ酸配列を含み、かつ、下記a)〜f):
a) (K/R)XXXDXXG(H/Y/S)(X*)、
b) KXXXDXXGX(X*)、
c) KAINDPVGH(X*)、
d) GH(X*)SRPDV、
e) DP(A/V)GH(X*)SRPDV(L/T)(S/R)L、
f) DPAGH(X*)SRPDVLSLLV、
よりなる群から選択された少なくとも1つの配列を含む、ニトリラーゼ活性を有するポリペプチドであり、ここで、Xは任意のアミノ酸を表し、前記単離されたポリペプチドに含まれる前記配列において、X*はシステイン、アラニン、アスパラギン、グリシン、セリン、フェニルアラニンおよびトレオニンよりなる群から選択されるものであり、ここで、X*は配列番号2に記載されている野生型Alcaligenes faecalisニトリラーゼ中の296番目の位置に相当する位置に存在するものである、
上記ポリペプチド。 - 前記ポリペプチドが配列番号2のアミノ酸配列に対して少なくとも90%同一なアミノ酸配列を含み、かつ、下記a)〜f):
a) (K/R)XXXDXXG(H/Y/S)(X*)、
b) KXXXDXXGX(X*)、
c) KAINDPVGH(X*)、
d) GH(X*)SRPDV、
e) DP(A/V)GH(X*)SRPDV(L/T)(S/R)L、
f) DPAGH(X*)SRPDVLSLLV、
よりなる群から選択された少なくとも1つの配列を含む、ニトリラーゼ活性を有するポリペプチドであり、ここで、Xは任意のアミノ酸を表し、前記単離されたポリペプチドに含まれる前記配列において、X*はシステイン、アラニン、アスパラギン、グリシン、セリン、フェニルアラニンおよびトレオニンよりなる群から選択されるものであり、ここで、X*は配列番号2に記載されている野生型Alcaligenes faecalisニトリラーゼ中の296番目の位置に相当する位置に存在するものである、請求項1に記載のポリペプチド。 - 請求項1または2に記載の単離されたポリペプチドであって、該ポリペプチドが、配列番号2に記載されている野生型Alcaligenes faecalisニトリラーゼ中の296番目の位置に相当する位置のアミノ酸残基を除いて該ニトリラーゼと同一のニトリラーゼと比較して、モジュレートされた基質許容性を示すニトリラーゼをコードする、上記ポリペプチド。
- 請求項1〜3のいずれか1項に記載のポリペプチドをコードする配列を含む、単離された核酸分子。
- 請求項4に記載の核酸を少なくとも1つ含む、組換え発現構築物。
- 少なくとも1つの請求項5に記載の組換え発現構築物および/または少なくとも1つの請求項4に記載の核酸を含む、組換え発現ベクター。
- 少なくとも1つの請求項6に記載の組換え発現ベクター、少なくとも1つの請求項5に記載の組換え発現構築物および/または少なくとも1つの請求項4に記載の核酸を含む、組換え非ヒト生物。
- 前記生物が、細菌、真菌、藻または植物生物よりなる群から選択される、請求項7に記載の組換え非ヒト生物。
- 細菌が、Escherichia、Rhodococcus、Nocardia、StreptomycesまたはMycobacterium属の細菌である、請求項8に記載の組換え非ヒト生物。
- モジュレートされた基質許容性を有するニトリラーゼの作製方法であって、該ニトリラーゼ中の、少なくとも配列番号2に記載されている野生型Alcaligenes faecalisニトリラーゼ中の296番目の位置に相当する位置のチロシンを、他のアミノ酸に置換するステップを少なくとも含む、上記方法であって、他のアミノ酸がシステイン、アラニン、アスパラギン、グリシン、セリン、フェニルアラニンおよびトレオニンよりなる群から選択される、方法。
- ニトリラーゼの基質許容性をモジュレートする方法であって、該ニトリラーゼ中の、少なくとも配列番号2に記載されている野生型Alcaligenes faecalisニトリラーゼ中の296番目の位置に相当する位置のチロシンを、他のアミノ酸に置換するステップを少なくとも含む、上記方法であって、他のアミノ酸がシステイン、アラニン、アスパラギン、グリシン、セリン、フェニルアラニンおよびトレオニンよりなる群から選択される、方法。
- カルボン酸を製造する方法であって、1つ以上の請求項1〜3のいずれか1項に記載のポリペプチドのうち1つ、または生長中の、休眠状態の、もしくは破壊された請求項7〜9のいずれか1項に記載の1種以上の組換え非ヒト生物のうち1つの作用によって、ニトリル、またはアルデヒドもしくはケトンおよびシアン化物の混合物を、対応するカルボン酸に変換するステップを含む、上記方法。
- 請求項12または13に記載の方法であって、ニトリルが、ラセミ体o-クロロマンデロニトリル、p-クロロマンデロニトリル、m-クロロマンデロニトリル、o-ブロモマンデロニトリル、p-ブロモマンデロニトリル、m-ブロモマンデロニトリル、o-メチルマンデロニトリル、p-メチルマンデロニトリルおよびm-メチルマンデロニトリル、ならびに本請求項のニトリルに対応するアルデヒドおよびシアン化物の混合物よりなる群から選択される、上記方法。
- 請求項12〜14のいずれか1項に記載の方法であって、製造される光学活性カルボン酸が、R-マンデル酸、S-マンデル酸、R-p-クロロマンデル酸、S-p-クロロマンデル酸、R-m-クロロマンデル酸、S-m-クロロマンデル酸、R-o-クロロマンデル酸、S-o-クロロマンデル酸、S-o-ブロモマンデル酸、S-p-ブロモマンデル酸、S-m-ブロモマンデル酸、S-o-メチルマンデル酸、S-p-メチルマンデル酸、S-m-メチルマンデル酸、R-o-ブロモマンデル酸、R-p-ブロモマンデル酸、R-m-ブロモマンデル酸、R-o-メチルマンデル酸、R-p-メチルマンデル酸およびR-m-メチルマンデル酸よりなる群から選択される、上記方法。
- 植物生物中の除草剤耐性を実現する方法であって、該植物生物が、配列番号2に記載されている野生型Alcaligenes faecalisニトリラーゼ中の296番目の位置に相当する位置において、チロシンでないアミノ酸を含むニトリラーゼをコードする核酸配列を含む発現カセットを用いてトランスフォームされており、前記核酸配列は前記植物生物におけるプロモーター機能の制御下にある、上記方法であって、チロシンでないアミノ酸がシステイン、アラニン、アスパラギン、グリシン、セリン、フェニルアラニンおよびトレオニンよりなる群から選択される、方法。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US45047003P | 2003-02-27 | 2003-02-27 | |
PCT/EP2004/001804 WO2004076655A1 (en) | 2003-02-27 | 2004-02-24 | Modified nitrilases and their use in methods for the production of carboxylic acids |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2006519002A JP2006519002A (ja) | 2006-08-24 |
JP4584242B2 true JP4584242B2 (ja) | 2010-11-17 |
Family
ID=32927657
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2006501937A Expired - Lifetime JP4584242B2 (ja) | 2003-02-27 | 2004-02-24 | 改変されたニトリラーゼおよびカルボン酸の製造方法におけるその使用 |
Country Status (8)
Country | Link |
---|---|
US (1) | US7985572B2 (ja) |
EP (1) | EP1599584B1 (ja) |
JP (1) | JP4584242B2 (ja) |
CN (1) | CN100445375C (ja) |
AT (1) | ATE435278T1 (ja) |
AU (1) | AU2004215238B2 (ja) |
DE (1) | DE602004021778D1 (ja) |
WO (1) | WO2004076655A1 (ja) |
Families Citing this family (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AT412092B (de) * | 2003-02-27 | 2004-09-27 | Dsm Fine Chem Austria Gmbh | Verfahren zur herstellung chiraler alpha-hydroxycarbonsäuren durch enzymatische hydrolyse von chiralen cyanhydrinen |
EP1966381A2 (de) * | 2005-12-20 | 2008-09-10 | Basf Se | Verfahren zur herstellung von 5-norbornen-2-carbonsäure aus 5-norbornen-2-carbonitril unter verwendung einer arylacetonitrilase |
AU2013243948A1 (en) * | 2012-04-02 | 2014-10-30 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of proteins associated with human disease |
US9303079B2 (en) | 2012-04-02 | 2016-04-05 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
US9283287B2 (en) | 2012-04-02 | 2016-03-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of nuclear proteins |
CN103898083B (zh) * | 2014-04-21 | 2016-06-29 | 武汉大学 | 一种新型水解酶超家族酰胺酶Azl13及其制备与应用 |
US9804036B2 (en) * | 2014-06-19 | 2017-10-31 | Infineon Technologies Ag | Temperature sensor calibration |
CN105130792A (zh) * | 2015-09-21 | 2015-12-09 | 上海佰瑞生物科技有限公司 | 一种对由生物法合成的(r)-(-)-扁桃酸进行分离纯化的方法 |
CN105349583A (zh) * | 2015-12-23 | 2016-02-24 | 武汉武药制药有限公司 | 一种酶法制备(r)-邻氯扁桃酸的方法及应用 |
CN106854673B (zh) * | 2016-12-23 | 2020-05-15 | 枣庄市杰诺生物酶有限公司 | 利用腈水解酶工程菌制备r-邻氯扁桃酸的方法 |
CN110205315B (zh) * | 2019-05-30 | 2021-01-01 | 中国石油大学(华东) | 腈水解酶XiNit2及其编码基因和应用 |
CN111471668B (zh) * | 2020-02-28 | 2022-05-24 | 浙江工业大学 | 一种腈水解酶突变体及其在制备1-氰基环己基乙酸中的应用 |
CN111662938B (zh) * | 2020-06-23 | 2021-05-04 | 浙江恒康药业股份有限公司 | 腈水合酶在催化氰基吡嗪类化合物水合反应生成酰胺吡嗪类化合物中的应用 |
Family Cites Families (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU611080B2 (en) | 1986-01-08 | 1991-06-06 | Rhone-Poulenc Agrochimie | Haloarylnitrile degrading gene, its use, and cells containing the same |
DE68926922T2 (de) | 1988-03-08 | 1996-12-19 | Japan Energy Corp | Verfahren zur Herstellung von L-alpha-Aminosäuren |
JP2623345B2 (ja) | 1988-06-27 | 1997-06-25 | 旭化成工業株式会社 | 光学活性なα―置換有機酸の製造方法 |
US5283193A (en) | 1988-06-27 | 1994-02-01 | Asahi Kasei Kogyo K.K. | Process for producing optically active α-substituted organic acid and microorganism and enzyme used therefor |
EP0449648B1 (en) | 1990-03-30 | 1999-05-12 | Nitto Chemical Industry Co., Ltd. | Process for producing R(-)-mandelic acid and derivatives thereof |
JP2974737B2 (ja) | 1990-08-16 | 1999-11-10 | 三菱レイヨン株式会社 | 光学活性乳酸の製造法 |
DK0549710T3 (da) | 1990-09-20 | 1996-03-18 | Du Pont | Fremgangsmåde til fremstilling af enantiomere 2-alkansyrer |
JP2676568B2 (ja) | 1991-06-26 | 1997-11-17 | 日東化学工業株式会社 | R(−)−マンデル酸およびその誘導体の製造法 |
JP2720140B2 (ja) | 1993-02-03 | 1998-02-25 | 日東化学工業株式会社 | フェニル基を有する光学活性α−ヒドロキシカルボン酸の製造法 |
JP3218133B2 (ja) | 1993-02-03 | 2001-10-15 | 三菱レイヨン株式会社 | フェニル基を有する光学活性α−ヒドロキシカルボン酸の製造法 |
JP3354688B2 (ja) | 1994-01-28 | 2002-12-09 | 三菱レイヨン株式会社 | 微生物によるα−ヒドロキシ酸またはα−ヒドロキシアミドの製造法 |
HU220860B1 (en) | 1994-09-22 | 2002-06-29 | Rhone Poulenc Nutrition Animal | Process for enzymatic hydrolysis of alpha-substituted 4-methyl-thiobutyronitriles |
JP3154633B2 (ja) * | 1994-12-28 | 2001-04-09 | 三菱レイヨン株式会社 | ニトリラーゼ遺伝子発現のための調節因子およびその遺伝子 |
JPH0937788A (ja) | 1995-07-31 | 1997-02-10 | Nitto Chem Ind Co Ltd | 新規なニトリラーゼ遺伝子 |
EP0974669B1 (en) | 1996-02-29 | 2007-05-02 | Nippon Soda Co., Ltd. | Process for preparing alpha-hydroxy acids using microorganism and novel microorganism |
FR2780416B1 (fr) | 1998-06-10 | 2002-12-20 | Rhone Poulenc Nutrition Animal | Procede industriel de production de proteines heterologues chez e. coli et souches utiles pour le procede |
DE19848129A1 (de) | 1998-10-19 | 2000-04-20 | Basf Ag | Verfahren zur Herstellung chiraler Carbonsäuren aus Nitrilen mit Hilfe einer Nitrilase oder Mikroorganismen, die ein Gen für die Nitrilase enthalten |
EA200100718A1 (ru) | 1999-10-26 | 2001-12-24 | Сова Денко К.К. | Новая бактерия rhodococcus, ген нитрилазы, ген нитрилгидратазы и ген амидазы бактерии rhodococcus и способ получения карбоновых кислот с их использованием |
FR2800749B1 (fr) | 1999-11-08 | 2004-07-16 | Rhone Poulenc Animal Nutrition | Procede de modulation de la selective des nitrilases, nouvelles nitrilases obtenues par ce procede et leur utilisation |
US7300775B2 (en) | 1999-12-29 | 2007-11-27 | Verenium Corporation | Methods for producing α-substituted carboxylic acids using nitrilases and strecker reagents |
DE10010149A1 (de) | 2000-03-03 | 2001-09-06 | Basf Ag | Nitrilase aus Rhodococcus rhodochrous NCIMB 11216 |
AU2001296653A1 (en) | 2000-10-04 | 2002-04-15 | Maxygen, Inc. | Enantioselective production of amino carboxylic acids |
JP2005501528A (ja) | 2001-06-05 | 2005-01-20 | エクセリクシス・インコーポレイテッド | p53経路のモディファイヤーとしてのGFATsおよび使用方法 |
EP1578910A4 (en) * | 2001-06-21 | 2008-06-04 | Verenium Corp | NITRILASES |
AU2003251523A1 (en) | 2002-06-13 | 2003-12-31 | Diversa Corporation | Processes for making (r)-ethyl 4-cyano-3-hydroxybutyric acid |
-
2004
- 2004-02-24 DE DE602004021778T patent/DE602004021778D1/de not_active Expired - Lifetime
- 2004-02-24 CN CNB2004800053978A patent/CN100445375C/zh not_active Expired - Lifetime
- 2004-02-24 US US10/546,611 patent/US7985572B2/en active Active
- 2004-02-24 JP JP2006501937A patent/JP4584242B2/ja not_active Expired - Lifetime
- 2004-02-24 WO PCT/EP2004/001804 patent/WO2004076655A1/en active Application Filing
- 2004-02-24 EP EP04713882A patent/EP1599584B1/en not_active Expired - Lifetime
- 2004-02-24 AU AU2004215238A patent/AU2004215238B2/en not_active Ceased
- 2004-02-24 AT AT04713882T patent/ATE435278T1/de active
Also Published As
Publication number | Publication date |
---|---|
AU2004215238B2 (en) | 2009-08-27 |
US7985572B2 (en) | 2011-07-26 |
CN100445375C (zh) | 2008-12-24 |
ATE435278T1 (de) | 2009-07-15 |
DE602004021778D1 (de) | 2009-08-13 |
AU2004215238A1 (en) | 2004-09-10 |
US20060259999A1 (en) | 2006-11-16 |
EP1599584B1 (en) | 2009-07-01 |
WO2004076655A1 (en) | 2004-09-10 |
EP1599584A1 (en) | 2005-11-30 |
CN1753990A (zh) | 2006-03-29 |
JP2006519002A (ja) | 2006-08-24 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP4584242B2 (ja) | 改変されたニトリラーゼおよびカルボン酸の製造方法におけるその使用 | |
US6869783B1 (en) | Method for producing chiral carboxylic acids from nitriles with the assistance of a nitrilase or microoganisms which contain a gene for the nitrilase | |
US6998258B1 (en) | L-pantolactone-hydrolase and a method for producing D-pantolactone | |
JP5793487B2 (ja) | アルドラーゼ、それらをコードする核酸ならびにそれらの作製および使用方法 | |
JP5563990B2 (ja) | トランスフェラーゼおよびオキシドレダクターゼ、それらをコードする核酸並びにそれらを製造および使用する方法 | |
JP2011078419A (ja) | スタチンおよびスタチン中間体の合成のための酵素化学的方法 | |
JP2005525102A (ja) | アミダーゼ、それをコードする核酸、および、それを作製および使用する方法 | |
WO2004085624A2 (en) | Transaminases, deaminases and aminomutases and compositions and methods for enzymatic detoxification | |
AU2001233802B2 (en) | Nitrilase from rhodococcus rhodochrous ncimb 11216 | |
Krammer et al. | A novel screening assay for hydroxynitrile lyases suitable for high-throughput screening | |
JP5260645B2 (ja) | 修飾13−ヒドロペルオキシドリアーゼおよびその使用 | |
EP1228198B1 (fr) | Procede de modulation de la selectivite des nitrilases, nitrilases obtenues par ce procede et leur utilisation | |
WO2004090124A2 (en) | Sequences encoding s-hydroxynitril lyases and their use in methods for the production of cyanohydrins | |
MXPA01003893A (en) | Method for producing chiral carboxylic acids from nitriles with the assistance of a nitrilase or microorganisms which contain a gene for the nitrilase | |
KR20040026672A (ko) | L-아미노산의 제조 방법 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20070220 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100105 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20100325 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20100401 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100705 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20100803 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20100901 |
|
R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 Ref document number: 4584242 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130910 Year of fee payment: 3 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |