CN109321610B - 微生物发酵法高效制备2-氨基-1,3-丙二醇 - Google Patents
微生物发酵法高效制备2-氨基-1,3-丙二醇 Download PDFInfo
- Publication number
- CN109321610B CN109321610B CN201811296012.8A CN201811296012A CN109321610B CN 109321610 B CN109321610 B CN 109321610B CN 201811296012 A CN201811296012 A CN 201811296012A CN 109321610 B CN109321610 B CN 109321610B
- Authority
- CN
- China
- Prior art keywords
- amino
- propanediol
- leu
- ala
- gly
- 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.)
- Active
Links
- KJJPLEZQSCZCKE-UHFFFAOYSA-N 2-aminopropane-1,3-diol Chemical compound OCC(N)CO KJJPLEZQSCZCKE-UHFFFAOYSA-N 0.000 title claims abstract description 93
- 238000000855 fermentation Methods 0.000 title claims abstract description 53
- 230000004151 fermentation Effects 0.000 title claims abstract description 53
- 238000000034 method Methods 0.000 title claims abstract description 24
- 230000000813 microbial effect Effects 0.000 title abstract description 7
- 238000002360 preparation method Methods 0.000 title description 9
- 108090000340 Transaminases Proteins 0.000 claims abstract description 40
- 102000003929 Transaminases Human genes 0.000 claims abstract description 39
- 230000000694 effects Effects 0.000 claims abstract description 25
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 7
- GNGACRATGGDKBX-UHFFFAOYSA-N dihydroxyacetone phosphate Chemical compound OCC(=O)COP(O)(O)=O GNGACRATGGDKBX-UHFFFAOYSA-N 0.000 claims description 78
- 241000588724 Escherichia coli Species 0.000 claims description 62
- 108010076573 phosphoserine phosphatase Proteins 0.000 claims description 28
- 101000950981 Bacillus subtilis (strain 168) Catabolic NAD-specific glutamate dehydrogenase RocG Proteins 0.000 claims description 27
- 102000016901 Glutamate dehydrogenase Human genes 0.000 claims description 27
- 102100021762 Phosphoserine phosphatase Human genes 0.000 claims description 27
- 150000001413 amino acids Chemical group 0.000 claims description 25
- 102000037865 fusion proteins Human genes 0.000 claims description 22
- 108020001507 fusion proteins Proteins 0.000 claims description 22
- 102000004190 Enzymes Human genes 0.000 claims description 18
- 108090000790 Enzymes Proteins 0.000 claims description 18
- 230000002708 enhancing effect Effects 0.000 claims description 18
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 15
- 241000894006 Bacteria Species 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 13
- WDWYJNPKBKWDBL-UHFFFAOYSA-N (2-amino-3-hydroxypropyl) dihydrogen phosphate Chemical compound OCC(N)COP(O)(O)=O WDWYJNPKBKWDBL-UHFFFAOYSA-N 0.000 claims description 10
- 230000004853 protein function Effects 0.000 claims description 10
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 8
- 239000008103 glucose Substances 0.000 claims description 8
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 claims description 7
- 241000206602 Eukaryota Species 0.000 claims description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 238000006209 dephosphorylation reaction Methods 0.000 claims description 4
- 238000012262 fermentative production Methods 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- -1 ammonium ion compound Chemical class 0.000 claims description 3
- 150000003868 ammonium compounds Chemical class 0.000 claims 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 claims description 2
- 238000012258 culturing Methods 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 108090000623 proteins and genes Proteins 0.000 abstract description 22
- 230000015572 biosynthetic process Effects 0.000 abstract description 19
- 238000003786 synthesis reaction Methods 0.000 abstract description 16
- 230000004927 fusion Effects 0.000 abstract description 10
- 102000004169 proteins and genes Human genes 0.000 abstract description 9
- 230000006696 biosynthetic metabolic pathway Effects 0.000 abstract description 7
- RXKJFZQQPQGTFL-UHFFFAOYSA-N dihydroxyacetone Chemical compound OCC(=O)CO RXKJFZQQPQGTFL-UHFFFAOYSA-N 0.000 abstract description 6
- 230000002194 synthesizing effect Effects 0.000 abstract description 6
- 230000003197 catalytic effect Effects 0.000 abstract description 4
- 238000010353 genetic engineering Methods 0.000 abstract description 4
- 229940120503 dihydroxyacetone Drugs 0.000 abstract description 3
- 238000013461 design Methods 0.000 abstract description 2
- 238000005516 engineering process Methods 0.000 abstract description 2
- 230000037353 metabolic pathway Effects 0.000 abstract description 2
- 238000005457 optimization Methods 0.000 abstract description 2
- 230000037361 pathway Effects 0.000 abstract 1
- 239000013612 plasmid Substances 0.000 description 34
- 239000000047 product Substances 0.000 description 17
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 11
- 238000010276 construction Methods 0.000 description 11
- 239000001963 growth medium Substances 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- 230000001131 transforming effect Effects 0.000 description 9
- 239000002994 raw material Substances 0.000 description 8
- 238000005891 transamination reaction Methods 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 7
- 241000589180 Rhizobium Species 0.000 description 6
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 6
- 230000014509 gene expression Effects 0.000 description 6
- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 6
- XKUKSGPZAADMRA-UHFFFAOYSA-N glycyl-glycyl-glycine Chemical compound NCC(=O)NCC(=O)NCC(O)=O XKUKSGPZAADMRA-UHFFFAOYSA-N 0.000 description 6
- 108010037850 glycylvaline Proteins 0.000 description 6
- 239000002773 nucleotide Substances 0.000 description 6
- 125000003729 nucleotide group Chemical group 0.000 description 6
- 230000002018 overexpression Effects 0.000 description 6
- 235000018102 proteins Nutrition 0.000 description 6
- 238000012216 screening Methods 0.000 description 6
- 229960002989 glutamic acid Drugs 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 108010090894 prolylleucine Proteins 0.000 description 5
- 108010061238 threonyl-glycine Proteins 0.000 description 5
- VYUXYMRNGALHEA-DLOVCJGASA-N His-Leu-Ala Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O VYUXYMRNGALHEA-DLOVCJGASA-N 0.000 description 4
- NEEOBPIXKWSBRF-IUCAKERBSA-N Leu-Glu-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O NEEOBPIXKWSBRF-IUCAKERBSA-N 0.000 description 4
- YBAFDPFAUTYYRW-UHFFFAOYSA-N N-L-alpha-glutamyl-L-leucine Natural products CC(C)CC(C(O)=O)NC(=O)C(N)CCC(O)=O YBAFDPFAUTYYRW-UHFFFAOYSA-N 0.000 description 4
- SITLTJHOQZFJGG-UHFFFAOYSA-N N-L-alpha-glutamyl-L-valine Natural products CC(C)C(C(O)=O)NC(=O)C(N)CCC(O)=O SITLTJHOQZFJGG-UHFFFAOYSA-N 0.000 description 4
- 229960005091 chloramphenicol Drugs 0.000 description 4
- 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 4
- 108010057821 leucylproline Proteins 0.000 description 4
- 239000002207 metabolite Substances 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- CIEYFQRZEULHJV-UHFFFAOYSA-N 1,1-dihydroxypropan-2-one;phosphoric acid Chemical compound OP(O)(O)=O.CC(=O)C(O)O CIEYFQRZEULHJV-UHFFFAOYSA-N 0.000 description 3
- PEIBBAXIKUAYGN-UBHSHLNASA-N Ala-Phe-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=CC=C1 PEIBBAXIKUAYGN-UBHSHLNASA-N 0.000 description 3
- 241000589173 Bradyrhizobium Species 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 3
- 241000192700 Cyanobacteria Species 0.000 description 3
- WGYHAAXZWPEBDQ-IFFSRLJSSA-N Glu-Val-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O WGYHAAXZWPEBDQ-IFFSRLJSSA-N 0.000 description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
- JBCLFWXMTIKCCB-UHFFFAOYSA-N H-Gly-Phe-OH Natural products NCC(=O)NC(C(O)=O)CC1=CC=CC=C1 JBCLFWXMTIKCCB-UHFFFAOYSA-N 0.000 description 3
- BCISUQVFDGYZBO-QSFUFRPTSA-N Ile-Val-Asp Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC(O)=O BCISUQVFDGYZBO-QSFUFRPTSA-N 0.000 description 3
- FADYJNXDPBKVCA-UHFFFAOYSA-N L-Phenylalanyl-L-lysin Natural products NCCCCC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FADYJNXDPBKVCA-UHFFFAOYSA-N 0.000 description 3
- UCRJTSIIAYHOHE-ULQDDVLXSA-N Leu-Tyr-Arg Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N UCRJTSIIAYHOHE-ULQDDVLXSA-N 0.000 description 3
- QESXLSQLQHHTIX-RHYQMDGZSA-N Leu-Val-Thr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QESXLSQLQHHTIX-RHYQMDGZSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 108010079364 N-glycylalanine Proteins 0.000 description 3
- 108010002311 N-glycylglutamic acid Proteins 0.000 description 3
- XUDRHBPSPAPDJP-SRVKXCTJSA-N Ser-Lys-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CO XUDRHBPSPAPDJP-SRVKXCTJSA-N 0.000 description 3
- COYHRQWNJDJCNA-NUJDXYNKSA-N Thr-Thr-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O COYHRQWNJDJCNA-NUJDXYNKSA-N 0.000 description 3
- 229940041514 candida albicans extract Drugs 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000008367 deionised water Substances 0.000 description 3
- 229910021641 deionized water Inorganic materials 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 108010063718 gamma-glutamylaspartic acid Proteins 0.000 description 3
- 230000034659 glycolysis Effects 0.000 description 3
- 108010050848 glycylleucine Proteins 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 108010040030 histidinoalanine Proteins 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 108010044374 isoleucyl-tyrosine Proteins 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
- 229960000318 kanamycin Drugs 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
- 229930182823 kanamycin A Natural products 0.000 description 3
- 108010083708 leucyl-aspartyl-valine Proteins 0.000 description 3
- 108010044311 leucyl-glycyl-glycine Proteins 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 108010029020 prolylglycine Proteins 0.000 description 3
- 108010048397 seryl-lysyl-leucine Proteins 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 235000013619 trace mineral Nutrition 0.000 description 3
- 239000011573 trace mineral Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 239000012138 yeast extract Substances 0.000 description 3
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
- ZDYNWWQXFRUOEO-XDTLVQLUSA-N Ala-Gln-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ZDYNWWQXFRUOEO-XDTLVQLUSA-N 0.000 description 2
- BGNLUHXLSAQYRQ-FXQIFTODSA-N Ala-Glu-Gln Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O BGNLUHXLSAQYRQ-FXQIFTODSA-N 0.000 description 2
- WGDNWOMKBUXFHR-BQBZGAKWSA-N Ala-Gly-Arg Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N WGDNWOMKBUXFHR-BQBZGAKWSA-N 0.000 description 2
- HQJKCXHQNUCKMY-GHCJXIJMSA-N Ala-Ile-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](C)N HQJKCXHQNUCKMY-GHCJXIJMSA-N 0.000 description 2
- DVJSJDDYCYSMFR-ZKWXMUAHSA-N Ala-Ile-Gly Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(O)=O DVJSJDDYCYSMFR-ZKWXMUAHSA-N 0.000 description 2
- SOBIAADAMRHGKH-CIUDSAMLSA-N Ala-Leu-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O SOBIAADAMRHGKH-CIUDSAMLSA-N 0.000 description 2
- SDZRIBWEVVRDQI-CIUDSAMLSA-N Ala-Lys-Asp Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(O)=O SDZRIBWEVVRDQI-CIUDSAMLSA-N 0.000 description 2
- XWFWAXPOLRTDFZ-FXQIFTODSA-N Ala-Pro-Ser Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O XWFWAXPOLRTDFZ-FXQIFTODSA-N 0.000 description 2
- VJVQKGYHIZPSNS-FXQIFTODSA-N Ala-Ser-Arg Chemical compound C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCN=C(N)N VJVQKGYHIZPSNS-FXQIFTODSA-N 0.000 description 2
- NCQMBSJGJMYKCK-ZLUOBGJFSA-N Ala-Ser-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O NCQMBSJGJMYKCK-ZLUOBGJFSA-N 0.000 description 2
- 241000219194 Arabidopsis Species 0.000 description 2
- XEPSCVXTCUUHDT-AVGNSLFASA-N Arg-Arg-Leu Natural products CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CCCN=C(N)N XEPSCVXTCUUHDT-AVGNSLFASA-N 0.000 description 2
- DXQIQUIQYAGRCC-CIUDSAMLSA-N Arg-Asp-Gln Chemical compound C(C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N)CN=C(N)N DXQIQUIQYAGRCC-CIUDSAMLSA-N 0.000 description 2
- OFIYLHVAAJYRBC-HJWJTTGWSA-N Arg-Ile-Phe Chemical compound CC[C@H](C)[C@H](NC(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](Cc1ccccc1)C(O)=O OFIYLHVAAJYRBC-HJWJTTGWSA-N 0.000 description 2
- NOZYDJOPOGKUSR-AVGNSLFASA-N Arg-Leu-Met Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(O)=O NOZYDJOPOGKUSR-AVGNSLFASA-N 0.000 description 2
- OMKZPCPZEFMBIT-SRVKXCTJSA-N Arg-Met-Arg Chemical compound NC(=N)NCCC[C@H](N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O OMKZPCPZEFMBIT-SRVKXCTJSA-N 0.000 description 2
- PBSQFBAJKPLRJY-BYULHYEWSA-N Asn-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CC(=O)N)N PBSQFBAJKPLRJY-BYULHYEWSA-N 0.000 description 2
- 244000063299 Bacillus subtilis Species 0.000 description 2
- 235000014469 Bacillus subtilis Nutrition 0.000 description 2
- OHLLDUNVMPPUMD-DCAQKATOSA-N Cys-Leu-Val Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](C(C)C)C(=O)O)NC(=O)[C@H](CS)N OHLLDUNVMPPUMD-DCAQKATOSA-N 0.000 description 2
- VIOQRFNAZDMVLO-NRPADANISA-N Cys-Val-Glu Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O VIOQRFNAZDMVLO-NRPADANISA-N 0.000 description 2
- XXLBHPPXDUWYAG-XQXXSGGOSA-N Gln-Ala-Thr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XXLBHPPXDUWYAG-XQXXSGGOSA-N 0.000 description 2
- JESJDAAGXULQOP-CIUDSAMLSA-N Gln-Arg-Ser Chemical compound C(C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCC(=O)N)N)CN=C(N)N JESJDAAGXULQOP-CIUDSAMLSA-N 0.000 description 2
- XJKAKYXMFHUIHT-AUTRQRHGSA-N Gln-Glu-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)N)N XJKAKYXMFHUIHT-AUTRQRHGSA-N 0.000 description 2
- WVYJNPCWJYBHJG-YVNDNENWSA-N Glu-Ile-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(O)=O WVYJNPCWJYBHJG-YVNDNENWSA-N 0.000 description 2
- ZIYGTCDTJJCDDP-JYJNAYRXSA-N Glu-Phe-Lys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)O)N ZIYGTCDTJJCDDP-JYJNAYRXSA-N 0.000 description 2
- YWAQATDNEKZFFK-BYPYZUCNSA-N Gly-Gly-Ser Chemical compound NCC(=O)NCC(=O)N[C@@H](CO)C(O)=O YWAQATDNEKZFFK-BYPYZUCNSA-N 0.000 description 2
- OMOZPGCHVWOXHN-BQBZGAKWSA-N Gly-Met-Ser Chemical compound CSCC[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)CN OMOZPGCHVWOXHN-BQBZGAKWSA-N 0.000 description 2
- CYHWWHKRCKHYGQ-GUBZILKMSA-N His-Cys-Glu Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N CYHWWHKRCKHYGQ-GUBZILKMSA-N 0.000 description 2
- OVPYIUNCVSOVNF-ZPFDUUQYSA-N Ile-Gln-Pro Natural products CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(O)=O OVPYIUNCVSOVNF-ZPFDUUQYSA-N 0.000 description 2
- LGMUPVWZEYYUMU-YVNDNENWSA-N Ile-Glu-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N LGMUPVWZEYYUMU-YVNDNENWSA-N 0.000 description 2
- PMGDADKJMCOXHX-UHFFFAOYSA-N L-Arginyl-L-glutamin-acetat Natural products NC(=N)NCCCC(N)C(=O)NC(CCC(N)=O)C(O)=O PMGDADKJMCOXHX-UHFFFAOYSA-N 0.000 description 2
- 241000880493 Leptailurus serval Species 0.000 description 2
- JKGHDYGZRDWHGA-SRVKXCTJSA-N Leu-Asn-Leu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O JKGHDYGZRDWHGA-SRVKXCTJSA-N 0.000 description 2
- QCSFMCFHVGTLFF-NHCYSSNCSA-N Leu-Asp-Val Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O QCSFMCFHVGTLFF-NHCYSSNCSA-N 0.000 description 2
- RVVBWTWPNFDYBE-SRVKXCTJSA-N Leu-Glu-Arg Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O RVVBWTWPNFDYBE-SRVKXCTJSA-N 0.000 description 2
- HPBCTWSUJOGJSH-MNXVOIDGSA-N Leu-Glu-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O HPBCTWSUJOGJSH-MNXVOIDGSA-N 0.000 description 2
- VWHGTYCRDRBSFI-ZETCQYMHSA-N Leu-Gly-Gly Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)NCC(O)=O VWHGTYCRDRBSFI-ZETCQYMHSA-N 0.000 description 2
- IEWBEPKLKUXQBU-VOAKCMCISA-N Leu-Leu-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O IEWBEPKLKUXQBU-VOAKCMCISA-N 0.000 description 2
- BGZCJDGBBUUBHA-KKUMJFAQSA-N Leu-Lys-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O BGZCJDGBBUUBHA-KKUMJFAQSA-N 0.000 description 2
- KWLWZYMNUZJKMZ-IHRRRGAJSA-N Leu-Pro-Leu Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O KWLWZYMNUZJKMZ-IHRRRGAJSA-N 0.000 description 2
- IDGZVZJLYFTXSL-DCAQKATOSA-N Leu-Ser-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCN=C(N)N IDGZVZJLYFTXSL-DCAQKATOSA-N 0.000 description 2
- XOWMDXHFSBCAKQ-SRVKXCTJSA-N Leu-Ser-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC(C)C XOWMDXHFSBCAKQ-SRVKXCTJSA-N 0.000 description 2
- WFCKERTZVCQXKH-KBPBESRZSA-N Leu-Tyr-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(O)=O WFCKERTZVCQXKH-KBPBESRZSA-N 0.000 description 2
- UYAKZHGIPRCGPF-CIUDSAMLSA-N Met-Glu-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)N UYAKZHGIPRCGPF-CIUDSAMLSA-N 0.000 description 2
- KSIPKXNIQOWMIC-RCWTZXSCSA-N Met-Thr-Arg Chemical compound CSCC[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CCCNC(N)=N KSIPKXNIQOWMIC-RCWTZXSCSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- CSYVXYQDIVCQNU-QWRGUYRKSA-N Phe-Asp-Gly Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O CSYVXYQDIVCQNU-QWRGUYRKSA-N 0.000 description 2
- XUSDDSLCRPUKLP-QXEWZRGKSA-N Pro-Asp-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H]1CCCN1 XUSDDSLCRPUKLP-QXEWZRGKSA-N 0.000 description 2
- XYSXOCIWCPFOCG-IHRRRGAJSA-N Pro-Leu-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O XYSXOCIWCPFOCG-IHRRRGAJSA-N 0.000 description 2
- XSXABUHLKPUVLX-JYJNAYRXSA-N Pro-Ser-Trp Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)O XSXABUHLKPUVLX-JYJNAYRXSA-N 0.000 description 2
- 241000589516 Pseudomonas Species 0.000 description 2
- FCRMLGJMPXCAHD-FXQIFTODSA-N Ser-Arg-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(O)=O FCRMLGJMPXCAHD-FXQIFTODSA-N 0.000 description 2
- KDGARKCAKHBEDB-NKWVEPMBSA-N Ser-Gly-Pro Chemical compound C1C[C@@H](N(C1)C(=O)CNC(=O)[C@H](CO)N)C(=O)O KDGARKCAKHBEDB-NKWVEPMBSA-N 0.000 description 2
- NQZFFLBPNDLTPO-DLOVCJGASA-N Ser-Phe-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CO)N NQZFFLBPNDLTPO-DLOVCJGASA-N 0.000 description 2
- XKFJENWJGHMDLI-QWRGUYRKSA-N Ser-Phe-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)NCC(O)=O XKFJENWJGHMDLI-QWRGUYRKSA-N 0.000 description 2
- QMCDMHWAKMUGJE-IHRRRGAJSA-N Ser-Phe-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O QMCDMHWAKMUGJE-IHRRRGAJSA-N 0.000 description 2
- WLJPJRGQRNCIQS-ZLUOBGJFSA-N Ser-Ser-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O WLJPJRGQRNCIQS-ZLUOBGJFSA-N 0.000 description 2
- 241001135312 Sinorhizobium Species 0.000 description 2
- 241000187747 Streptomyces Species 0.000 description 2
- CEXFELBFVHLYDZ-XGEHTFHBSA-N Thr-Arg-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O CEXFELBFVHLYDZ-XGEHTFHBSA-N 0.000 description 2
- AQAMPXBRJJWPNI-JHEQGTHGSA-N Thr-Gly-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O AQAMPXBRJJWPNI-JHEQGTHGSA-N 0.000 description 2
- RFKVQLIXNVEOMB-WEDXCCLWSA-N Thr-Leu-Gly Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)O)N)O RFKVQLIXNVEOMB-WEDXCCLWSA-N 0.000 description 2
- KRDSCBLRHORMRK-JXUBOQSCSA-N Thr-Lys-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O KRDSCBLRHORMRK-JXUBOQSCSA-N 0.000 description 2
- CYCGARJWIQWPQM-YJRXYDGGSA-N Thr-Tyr-Ser Chemical compound C[C@@H](O)[C@H]([NH3+])C(=O)N[C@H](C(=O)N[C@@H](CO)C([O-])=O)CC1=CC=C(O)C=C1 CYCGARJWIQWPQM-YJRXYDGGSA-N 0.000 description 2
- TWJDQTTXXZDJKV-BPUTZDHNSA-N Trp-Arg-Ser Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O TWJDQTTXXZDJKV-BPUTZDHNSA-N 0.000 description 2
- RWAYYYOZMHMEGD-XIRDDKMYSA-N Trp-Leu-Ser Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O)=CNC2=C1 RWAYYYOZMHMEGD-XIRDDKMYSA-N 0.000 description 2
- GIOBXJSONRQHKQ-RYUDHWBXSA-N Tyr-Gly-Glu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O GIOBXJSONRQHKQ-RYUDHWBXSA-N 0.000 description 2
- IGXLNVIYDYONFB-UFYCRDLUSA-N Tyr-Phe-Arg Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)C1=CC=C(O)C=C1 IGXLNVIYDYONFB-UFYCRDLUSA-N 0.000 description 2
- TYFLVOUZHQUBGM-IHRRRGAJSA-N Tyr-Ser-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 TYFLVOUZHQUBGM-IHRRRGAJSA-N 0.000 description 2
- YFOCMOVJBQDBCE-NRPADANISA-N Val-Ala-Glu Chemical compound C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](C(C)C)N YFOCMOVJBQDBCE-NRPADANISA-N 0.000 description 2
- XJFXZQKJQGYFMM-GUBZILKMSA-N Val-Cys-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)O)N XJFXZQKJQGYFMM-GUBZILKMSA-N 0.000 description 2
- XGJLNBNZNMVJRS-NRPADANISA-N Val-Glu-Ala Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O XGJLNBNZNMVJRS-NRPADANISA-N 0.000 description 2
- GVJUTBOZZBTBIG-AVGNSLFASA-N Val-Lys-Arg Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N GVJUTBOZZBTBIG-AVGNSLFASA-N 0.000 description 2
- XPKCFQZDQGVJCX-RHYQMDGZSA-N Val-Lys-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C(C)C)N)O XPKCFQZDQGVJCX-RHYQMDGZSA-N 0.000 description 2
- USLVEJAHTBLSIL-CYDGBPFRSA-N Val-Pro-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)C(C)C USLVEJAHTBLSIL-CYDGBPFRSA-N 0.000 description 2
- GBIUHAYJGWVNLN-UHFFFAOYSA-N Val-Ser-Pro Natural products CC(C)C(N)C(=O)NC(CO)C(=O)N1CCCC1C(O)=O GBIUHAYJGWVNLN-UHFFFAOYSA-N 0.000 description 2
- LLJLBRRXKZTTRD-GUBZILKMSA-N Val-Val-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(=O)O)N LLJLBRRXKZTTRD-GUBZILKMSA-N 0.000 description 2
- 108010047495 alanylglycine Proteins 0.000 description 2
- 108010070944 alanylhistidine Proteins 0.000 description 2
- 108010050025 alpha-glutamyltryptophan Proteins 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 229960000723 ampicillin Drugs 0.000 description 2
- 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 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 108010080488 arginyl-arginyl-leucine Proteins 0.000 description 2
- 108010008355 arginyl-glutamine Proteins 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 108010078144 glutaminyl-glycine Proteins 0.000 description 2
- 108010090037 glycyl-alanyl-isoleucine Proteins 0.000 description 2
- 108010033719 glycyl-histidyl-glycine Proteins 0.000 description 2
- 108010015792 glycyllysine Proteins 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- XQZXYNRDCRIARQ-LURJTMIESA-N iopamidol Chemical compound C[C@H](O)C(=O)NC1=C(I)C(C(=O)NC(CO)CO)=C(I)C(C(=O)NC(CO)CO)=C1I XQZXYNRDCRIARQ-LURJTMIESA-N 0.000 description 2
- 229960004647 iopamidol Drugs 0.000 description 2
- 108010034529 leucyl-lysine Proteins 0.000 description 2
- 108010009298 lysylglutamic acid Proteins 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 108010005942 methionylglycine Proteins 0.000 description 2
- 210000004898 n-terminal fragment Anatomy 0.000 description 2
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 2
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 108010070409 phenylalanyl-glycyl-glycine Proteins 0.000 description 2
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 2
- 108010007513 prolyl-glycyl-prolyl-leucine Proteins 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- NWSCUKIRCCHDHL-UHFFFAOYSA-N sodium;3-hydroxy-2-nitropropan-1-olate Chemical compound [Na+].OCC(C[O-])[N+]([O-])=O NWSCUKIRCCHDHL-UHFFFAOYSA-N 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 230000005026 transcription initiation Effects 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 238000009423 ventilation Methods 0.000 description 2
- BLHMJKUCBVSLQC-UHFFFAOYSA-N 2,2-dimethyl-5-nitro-1,3-dioxane Chemical compound CC1(C)OCC([N+]([O-])=O)CO1 BLHMJKUCBVSLQC-UHFFFAOYSA-N 0.000 description 1
- KPGXRSRHYNQIFN-UHFFFAOYSA-L 2-oxoglutarate(2-) Chemical compound [O-]C(=O)CCC(=O)C([O-])=O KPGXRSRHYNQIFN-UHFFFAOYSA-L 0.000 description 1
- WAYGJJPORXLBHU-UHFFFAOYSA-N 5-nitro-1,3-dioxane Chemical compound [O-][N+](=O)C1COCOC1 WAYGJJPORXLBHU-UHFFFAOYSA-N 0.000 description 1
- PAHMYIHLZQRVHU-UHFFFAOYSA-N 6-ethylpiperidin-2-one Chemical compound CCC1CCCC(=O)N1 PAHMYIHLZQRVHU-UHFFFAOYSA-N 0.000 description 1
- HHGYNJRJIINWAK-FXQIFTODSA-N Ala-Ala-Arg Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N HHGYNJRJIINWAK-FXQIFTODSA-N 0.000 description 1
- RLMISHABBKUNFO-WHFBIAKZSA-N Ala-Ala-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O RLMISHABBKUNFO-WHFBIAKZSA-N 0.000 description 1
- KQFRUSHJPKXBMB-BHDSKKPTSA-N Ala-Ala-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](C)NC(=O)[C@@H](N)C)C(O)=O)=CNC2=C1 KQFRUSHJPKXBMB-BHDSKKPTSA-N 0.000 description 1
- JAMAWBXXKFGFGX-KZVJFYERSA-N Ala-Arg-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O JAMAWBXXKFGFGX-KZVJFYERSA-N 0.000 description 1
- YAXNATKKPOWVCP-ZLUOBGJFSA-N Ala-Asn-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(O)=O YAXNATKKPOWVCP-ZLUOBGJFSA-N 0.000 description 1
- CVGNCMIULZNYES-WHFBIAKZSA-N Ala-Asn-Gly Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O CVGNCMIULZNYES-WHFBIAKZSA-N 0.000 description 1
- STACJSVFHSEZJV-GHCJXIJMSA-N Ala-Asn-Ile Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O STACJSVFHSEZJV-GHCJXIJMSA-N 0.000 description 1
- KIUYPHAMDKDICO-WHFBIAKZSA-N Ala-Asp-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O KIUYPHAMDKDICO-WHFBIAKZSA-N 0.000 description 1
- YSMPVONNIWLJML-FXQIFTODSA-N Ala-Asp-Pro Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(O)=O YSMPVONNIWLJML-FXQIFTODSA-N 0.000 description 1
- CSAHOYQKNHGDHX-ACZMJKKPSA-N Ala-Gln-Asn Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O CSAHOYQKNHGDHX-ACZMJKKPSA-N 0.000 description 1
- SFNFGFDRYJKZKN-XQXXSGGOSA-N Ala-Gln-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](C)N)O SFNFGFDRYJKZKN-XQXXSGGOSA-N 0.000 description 1
- GGNHBHYDMUDXQB-KBIXCLLPSA-N Ala-Glu-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)N GGNHBHYDMUDXQB-KBIXCLLPSA-N 0.000 description 1
- HXNNRBHASOSVPG-GUBZILKMSA-N Ala-Glu-Leu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O HXNNRBHASOSVPG-GUBZILKMSA-N 0.000 description 1
- XYTNPQNAZREREP-XQXXSGGOSA-N Ala-Glu-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XYTNPQNAZREREP-XQXXSGGOSA-N 0.000 description 1
- CWEAKSWWKHGTRJ-BQBZGAKWSA-N Ala-Gly-Met Chemical compound [H]N[C@@H](C)C(=O)NCC(=O)N[C@@H](CCSC)C(O)=O CWEAKSWWKHGTRJ-BQBZGAKWSA-N 0.000 description 1
- NBTGEURICRTMGL-WHFBIAKZSA-N Ala-Gly-Ser Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O NBTGEURICRTMGL-WHFBIAKZSA-N 0.000 description 1
- OBVSBEYOMDWLRJ-BFHQHQDPSA-N Ala-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@H](C)N OBVSBEYOMDWLRJ-BFHQHQDPSA-N 0.000 description 1
- NIZKGBJVCMRDKO-KWQFWETISA-N Ala-Gly-Tyr Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 NIZKGBJVCMRDKO-KWQFWETISA-N 0.000 description 1
- SMCGQGDVTPFXKB-XPUUQOCRSA-N Ala-Gly-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@H](C)N SMCGQGDVTPFXKB-XPUUQOCRSA-N 0.000 description 1
- IVKWMMGFLAMMKJ-XVYDVKMFSA-N Ala-His-Asn Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CC(=O)N)C(=O)O)N IVKWMMGFLAMMKJ-XVYDVKMFSA-N 0.000 description 1
- PNALXAODQKTNLV-JBDRJPRFSA-N Ala-Ile-Ala Chemical compound C[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O PNALXAODQKTNLV-JBDRJPRFSA-N 0.000 description 1
- CKLDHDOIYBVUNP-KBIXCLLPSA-N Ala-Ile-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(O)=O CKLDHDOIYBVUNP-KBIXCLLPSA-N 0.000 description 1
- CFPQUJZTLUQUTJ-HTFCKZLJSA-N Ala-Ile-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](C)N CFPQUJZTLUQUTJ-HTFCKZLJSA-N 0.000 description 1
- LXAARTARZJJCMB-CIQUZCHMSA-N Ala-Ile-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O LXAARTARZJJCMB-CIQUZCHMSA-N 0.000 description 1
- PMQXMXAASGFUDX-SRVKXCTJSA-N Ala-Lys-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](C)N)CCCCN PMQXMXAASGFUDX-SRVKXCTJSA-N 0.000 description 1
- CHFFHQUVXHEGBY-GARJFASQSA-N Ala-Lys-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@@H]1C(=O)O)N CHFFHQUVXHEGBY-GARJFASQSA-N 0.000 description 1
- NLOMBWNGESDVJU-GUBZILKMSA-N Ala-Met-Arg Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O NLOMBWNGESDVJU-GUBZILKMSA-N 0.000 description 1
- XSTZMVAYYCJTNR-DCAQKATOSA-N Ala-Met-Leu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(O)=O XSTZMVAYYCJTNR-DCAQKATOSA-N 0.000 description 1
- ADSGHMXEAZJJNF-DCAQKATOSA-N Ala-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)N ADSGHMXEAZJJNF-DCAQKATOSA-N 0.000 description 1
- RMAWDDRDTRSZIR-ZLUOBGJFSA-N Ala-Ser-Asp Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O RMAWDDRDTRSZIR-ZLUOBGJFSA-N 0.000 description 1
- HOVPGJUNRLMIOZ-CIUDSAMLSA-N Ala-Ser-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](C)N HOVPGJUNRLMIOZ-CIUDSAMLSA-N 0.000 description 1
- NZGRHTKZFSVPAN-BIIVOSGPSA-N Ala-Ser-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CO)C(=O)N1CCC[C@@H]1C(=O)O)N NZGRHTKZFSVPAN-BIIVOSGPSA-N 0.000 description 1
- LSMDIAAALJJLRO-XQXXSGGOSA-N Ala-Thr-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O LSMDIAAALJJLRO-XQXXSGGOSA-N 0.000 description 1
- IOFVWPYSRSCWHI-JXUBOQSCSA-N Ala-Thr-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](C)N IOFVWPYSRSCWHI-JXUBOQSCSA-N 0.000 description 1
- KTXKIYXZQFWJKB-VZFHVOOUSA-N Ala-Thr-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O KTXKIYXZQFWJKB-VZFHVOOUSA-N 0.000 description 1
- PGNNQOJOEGFAOR-KWQFWETISA-N Ala-Tyr-Gly Chemical compound OC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=C(O)C=C1 PGNNQOJOEGFAOR-KWQFWETISA-N 0.000 description 1
- VYMJAWXRWHJIMS-LKTVYLICSA-N Ala-Tyr-His Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)N VYMJAWXRWHJIMS-LKTVYLICSA-N 0.000 description 1
- 241000605317 Anaplasmataceae Species 0.000 description 1
- PEFFAAKJGBZBKL-NAKRPEOUSA-N Arg-Ala-Ile Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O PEFFAAKJGBZBKL-NAKRPEOUSA-N 0.000 description 1
- OTOXOKCIIQLMFH-KZVJFYERSA-N Arg-Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCN=C(N)N OTOXOKCIIQLMFH-KZVJFYERSA-N 0.000 description 1
- IASNWHAGGYTEKX-IUCAKERBSA-N Arg-Arg-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(O)=O IASNWHAGGYTEKX-IUCAKERBSA-N 0.000 description 1
- OVVUNXXROOFSIM-SDDRHHMPSA-N Arg-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O OVVUNXXROOFSIM-SDDRHHMPSA-N 0.000 description 1
- DCGLNNVKIZXQOJ-FXQIFTODSA-N Arg-Asn-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCCN=C(N)N)N DCGLNNVKIZXQOJ-FXQIFTODSA-N 0.000 description 1
- CPSHGRGUPZBMOK-CIUDSAMLSA-N Arg-Asn-Gln Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O CPSHGRGUPZBMOK-CIUDSAMLSA-N 0.000 description 1
- KMSHNDWHPWXPEC-BQBZGAKWSA-N Arg-Asp-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O KMSHNDWHPWXPEC-BQBZGAKWSA-N 0.000 description 1
- CYXCAHZVPFREJD-LURJTMIESA-N Arg-Gly-Gly Chemical compound NC(=N)NCCC[C@H](N)C(=O)NCC(=O)NCC(O)=O CYXCAHZVPFREJD-LURJTMIESA-N 0.000 description 1
- OQCWXQJLCDPRHV-UWVGGRQHSA-N Arg-Gly-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O OQCWXQJLCDPRHV-UWVGGRQHSA-N 0.000 description 1
- SLNCSSWAIDUUGF-LSJOCFKGSA-N Arg-His-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(O)=O SLNCSSWAIDUUGF-LSJOCFKGSA-N 0.000 description 1
- MSILNNHVVMMTHZ-UWVGGRQHSA-N Arg-His-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CN=CN1 MSILNNHVVMMTHZ-UWVGGRQHSA-N 0.000 description 1
- NIUDXSFNLBIWOB-DCAQKATOSA-N Arg-Leu-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N NIUDXSFNLBIWOB-DCAQKATOSA-N 0.000 description 1
- WMEVEPXNCMKNGH-IHRRRGAJSA-N Arg-Leu-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N WMEVEPXNCMKNGH-IHRRRGAJSA-N 0.000 description 1
- JEOCWTUOMKEEMF-RHYQMDGZSA-N Arg-Leu-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O JEOCWTUOMKEEMF-RHYQMDGZSA-N 0.000 description 1
- OGSQONVYSTZIJB-WDSOQIARSA-N Arg-Leu-Trp Chemical compound CC(C)C[C@H](NC(=O)[C@@H](N)CCCN=C(N)N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(O)=O OGSQONVYSTZIJB-WDSOQIARSA-N 0.000 description 1
- DIIGDGJKTMLQQW-IHRRRGAJSA-N Arg-Lys-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCN=C(N)N)N DIIGDGJKTMLQQW-IHRRRGAJSA-N 0.000 description 1
- NYDIVDKTULRINZ-AVGNSLFASA-N Arg-Met-Lys Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N NYDIVDKTULRINZ-AVGNSLFASA-N 0.000 description 1
- BSGSDLYGGHGMND-IHRRRGAJSA-N Arg-Phe-Cys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N BSGSDLYGGHGMND-IHRRRGAJSA-N 0.000 description 1
- JPAWCMXVNZPJLO-IHRRRGAJSA-N Arg-Ser-Phe Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O JPAWCMXVNZPJLO-IHRRRGAJSA-N 0.000 description 1
- ZJBUILVYSXQNSW-YTWAJWBKSA-N Arg-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)O ZJBUILVYSXQNSW-YTWAJWBKSA-N 0.000 description 1
- LLQIAIUAKGNOSE-NHCYSSNCSA-N Arg-Val-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCCN=C(N)N LLQIAIUAKGNOSE-NHCYSSNCSA-N 0.000 description 1
- VYZBPPBKFCHCIS-WPRPVWTQSA-N Arg-Val-Gly Chemical compound OC(=O)CNC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCCN=C(N)N VYZBPPBKFCHCIS-WPRPVWTQSA-N 0.000 description 1
- CPTXATAOUQJQRO-GUBZILKMSA-N Arg-Val-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O CPTXATAOUQJQRO-GUBZILKMSA-N 0.000 description 1
- PFOYSEIHFVKHNF-FXQIFTODSA-N Asn-Ala-Arg Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O PFOYSEIHFVKHNF-FXQIFTODSA-N 0.000 description 1
- VDCIPFYVCICPEC-FXQIFTODSA-N Asn-Arg-Ala Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O VDCIPFYVCICPEC-FXQIFTODSA-N 0.000 description 1
- UGXVKHRDGLYFKR-CIUDSAMLSA-N Asn-Asp-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC(N)=O UGXVKHRDGLYFKR-CIUDSAMLSA-N 0.000 description 1
- QNJIRRVTOXNGMH-GUBZILKMSA-N Asn-Gln-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(N)=O QNJIRRVTOXNGMH-GUBZILKMSA-N 0.000 description 1
- IBLAOXSULLECQZ-IUKAMOBKSA-N Asn-Ile-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CC(N)=O IBLAOXSULLECQZ-IUKAMOBKSA-N 0.000 description 1
- SPCONPVIDFMDJI-QSFUFRPTSA-N Asn-Ile-Val Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(O)=O SPCONPVIDFMDJI-QSFUFRPTSA-N 0.000 description 1
- GLWFAWNYGWBMOC-SRVKXCTJSA-N Asn-Leu-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O GLWFAWNYGWBMOC-SRVKXCTJSA-N 0.000 description 1
- JLNFZLNDHONLND-GARJFASQSA-N Asn-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(=O)N)N JLNFZLNDHONLND-GARJFASQSA-N 0.000 description 1
- DJIMLSXHXKWADV-CIUDSAMLSA-N Asn-Leu-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(N)=O DJIMLSXHXKWADV-CIUDSAMLSA-N 0.000 description 1
- OSZBYGVKAFZWKC-FXQIFTODSA-N Asn-Pro-Cys Chemical compound NC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CS)C(O)=O OSZBYGVKAFZWKC-FXQIFTODSA-N 0.000 description 1
- GKKUBLFXKRDMFC-BQBZGAKWSA-N Asn-Pro-Gly Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O GKKUBLFXKRDMFC-BQBZGAKWSA-N 0.000 description 1
- AWXDRZJQCVHCIT-DCAQKATOSA-N Asn-Pro-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CC(N)=O AWXDRZJQCVHCIT-DCAQKATOSA-N 0.000 description 1
- VHQSGALUSWIYOD-QXEWZRGKSA-N Asn-Pro-Val Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O VHQSGALUSWIYOD-QXEWZRGKSA-N 0.000 description 1
- HPNDKUOLNRVRAY-BIIVOSGPSA-N Asn-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CC(=O)N)N)C(=O)O HPNDKUOLNRVRAY-BIIVOSGPSA-N 0.000 description 1
- WLVLIYYBPPONRJ-GCJQMDKQSA-N Asn-Thr-Ala Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O WLVLIYYBPPONRJ-GCJQMDKQSA-N 0.000 description 1
- XCBKBPRFACFFOO-AQZXSJQPSA-N Asn-Thr-Trp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CC(=O)N)N)O XCBKBPRFACFFOO-AQZXSJQPSA-N 0.000 description 1
- JZLFYAAGGYMRIK-BYULHYEWSA-N Asn-Val-Asp Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O JZLFYAAGGYMRIK-BYULHYEWSA-N 0.000 description 1
- ZAESWDKAMDVHLL-RCOVLWMOSA-N Asn-Val-Gly Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O ZAESWDKAMDVHLL-RCOVLWMOSA-N 0.000 description 1
- LMIWYCWRJVMAIQ-NHCYSSNCSA-N Asn-Val-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)N)N LMIWYCWRJVMAIQ-NHCYSSNCSA-N 0.000 description 1
- KRXIWXCXOARFNT-ZLUOBGJFSA-N Asp-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O KRXIWXCXOARFNT-ZLUOBGJFSA-N 0.000 description 1
- KDFQZBWWPYQBEN-ZLUOBGJFSA-N Asp-Ala-Asn Chemical compound C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CC(=O)O)N KDFQZBWWPYQBEN-ZLUOBGJFSA-N 0.000 description 1
- GWTLRDMPMJCNMH-WHFBIAKZSA-N Asp-Asn-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O GWTLRDMPMJCNMH-WHFBIAKZSA-N 0.000 description 1
- JGDBHIVECJGXJA-FXQIFTODSA-N Asp-Asp-Arg Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O JGDBHIVECJGXJA-FXQIFTODSA-N 0.000 description 1
- SBHUBSDEZQFJHJ-CIUDSAMLSA-N Asp-Asp-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC(O)=O SBHUBSDEZQFJHJ-CIUDSAMLSA-N 0.000 description 1
- NYQHSUGFEWDWPD-ACZMJKKPSA-N Asp-Gln-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC(=O)O)N NYQHSUGFEWDWPD-ACZMJKKPSA-N 0.000 description 1
- KIJLEFNHWSXHRU-NUMRIWBASA-N Asp-Gln-Thr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KIJLEFNHWSXHRU-NUMRIWBASA-N 0.000 description 1
- VAWNQIGQPUOPQW-ACZMJKKPSA-N Asp-Glu-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O VAWNQIGQPUOPQW-ACZMJKKPSA-N 0.000 description 1
- HSWYMWGDMPLTTH-FXQIFTODSA-N Asp-Glu-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O HSWYMWGDMPLTTH-FXQIFTODSA-N 0.000 description 1
- VILLWIDTHYPSLC-PEFMBERDSA-N Asp-Glu-Ile Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O VILLWIDTHYPSLC-PEFMBERDSA-N 0.000 description 1
- DGKCOYGQLNWNCJ-ACZMJKKPSA-N Asp-Glu-Ser Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O DGKCOYGQLNWNCJ-ACZMJKKPSA-N 0.000 description 1
- DTNUIAJCPRMNBT-WHFBIAKZSA-N Asp-Gly-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](C)C(O)=O DTNUIAJCPRMNBT-WHFBIAKZSA-N 0.000 description 1
- KFAFUJMGHVVYRC-DCAQKATOSA-N Asp-Leu-Met Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(O)=O KFAFUJMGHVVYRC-DCAQKATOSA-N 0.000 description 1
- UMHUHHJMEXNSIV-CIUDSAMLSA-N Asp-Leu-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(O)=O UMHUHHJMEXNSIV-CIUDSAMLSA-N 0.000 description 1
- QNIACYURSSCLRP-GUBZILKMSA-N Asp-Lys-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O QNIACYURSSCLRP-GUBZILKMSA-N 0.000 description 1
- NZWDWXSWUQCNMG-GARJFASQSA-N Asp-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)N)C(=O)O NZWDWXSWUQCNMG-GARJFASQSA-N 0.000 description 1
- WWOYXVBGHAHQBG-FXQIFTODSA-N Asp-Met-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(O)=O WWOYXVBGHAHQBG-FXQIFTODSA-N 0.000 description 1
- WOPJVEMFXYHZEE-SRVKXCTJSA-N Asp-Phe-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O WOPJVEMFXYHZEE-SRVKXCTJSA-N 0.000 description 1
- USNJAPJZSGTTPX-XVSYOHENSA-N Asp-Phe-Thr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O USNJAPJZSGTTPX-XVSYOHENSA-N 0.000 description 1
- IWLZBRTUIVXZJD-OLHMAJIHSA-N Asp-Thr-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(O)=O IWLZBRTUIVXZJD-OLHMAJIHSA-N 0.000 description 1
- OYSYWMMZGJSQRB-AVGNSLFASA-N Asp-Tyr-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O OYSYWMMZGJSQRB-AVGNSLFASA-N 0.000 description 1
- ZQFZEBRNAMXXJV-KKUMJFAQSA-N Asp-Tyr-His Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)NC(=O)[C@H](CC(=O)O)N)O ZQFZEBRNAMXXJV-KKUMJFAQSA-N 0.000 description 1
- QOJJMJKTMKNFEF-ZKWXMUAHSA-N Asp-Val-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CC(O)=O QOJJMJKTMKNFEF-ZKWXMUAHSA-N 0.000 description 1
- 239000002028 Biomass Substances 0.000 description 1
- 241001148114 Bradyrhizobium elkanii Species 0.000 description 1
- YFXFOZPXVFPBDH-VZFHVOOUSA-N Cys-Ala-Thr Chemical compound C[C@@H](O)[C@H](NC(=O)[C@H](C)NC(=O)[C@@H](N)CS)C(O)=O YFXFOZPXVFPBDH-VZFHVOOUSA-N 0.000 description 1
- OTXLNICGSXPGQF-KBIXCLLPSA-N Cys-Ile-Glu Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(O)=O OTXLNICGSXPGQF-KBIXCLLPSA-N 0.000 description 1
- ZMWOJVAXTOUHAP-ZKWXMUAHSA-N Cys-Ile-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CS)N ZMWOJVAXTOUHAP-ZKWXMUAHSA-N 0.000 description 1
- OXFOKRAFNYSREH-BJDJZHNGSA-N Cys-Ile-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)O)NC(=O)[C@H](CS)N OXFOKRAFNYSREH-BJDJZHNGSA-N 0.000 description 1
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 101150099894 GDHA gene Proteins 0.000 description 1
- DTCCMDYODDPHBG-ACZMJKKPSA-N Gln-Ala-Cys Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CS)C(O)=O DTCCMDYODDPHBG-ACZMJKKPSA-N 0.000 description 1
- HHWQMFIGMMOVFK-WDSKDSINSA-N Gln-Ala-Gly Chemical compound OC(=O)CNC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(N)=O HHWQMFIGMMOVFK-WDSKDSINSA-N 0.000 description 1
- KVYVOGYEMPEXBT-GUBZILKMSA-N Gln-Ala-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(N)=O KVYVOGYEMPEXBT-GUBZILKMSA-N 0.000 description 1
- PHZYLYASFWHLHJ-FXQIFTODSA-N Gln-Asn-Glu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O PHZYLYASFWHLHJ-FXQIFTODSA-N 0.000 description 1
- IVCOYUURLWQDJQ-LPEHRKFASA-N Gln-Gln-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)N)N)C(=O)O IVCOYUURLWQDJQ-LPEHRKFASA-N 0.000 description 1
- VOLVNCMGXWDDQY-LPEHRKFASA-N Gln-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)N)N)C(=O)O VOLVNCMGXWDDQY-LPEHRKFASA-N 0.000 description 1
- IOFDDSNZJDIGPB-GVXVVHGQSA-N Gln-Leu-Val Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O IOFDDSNZJDIGPB-GVXVVHGQSA-N 0.000 description 1
- SYZZMPFLOLSMHL-XHNCKOQMSA-N Gln-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)N)N)C(=O)O SYZZMPFLOLSMHL-XHNCKOQMSA-N 0.000 description 1
- RONJIBWTGKVKFY-HTUGSXCWSA-N Gln-Thr-Phe Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CCC(=O)N)N)O RONJIBWTGKVKFY-HTUGSXCWSA-N 0.000 description 1
- CMBXOSFZCFGDLE-IHRRRGAJSA-N Gln-Tyr-Gln Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CCC(=O)N)N)O CMBXOSFZCFGDLE-IHRRRGAJSA-N 0.000 description 1
- OGMQXTXGLDNBSS-FXQIFTODSA-N Glu-Ala-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(O)=O OGMQXTXGLDNBSS-FXQIFTODSA-N 0.000 description 1
- FYBSCGZLICNOBA-XQXXSGGOSA-N Glu-Ala-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O FYBSCGZLICNOBA-XQXXSGGOSA-N 0.000 description 1
- NLKVNZUFDPWPNL-YUMQZZPRSA-N Glu-Arg-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O NLKVNZUFDPWPNL-YUMQZZPRSA-N 0.000 description 1
- XKPOCESCRTVRPL-KBIXCLLPSA-N Glu-Cys-Ile Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O XKPOCESCRTVRPL-KBIXCLLPSA-N 0.000 description 1
- CGOHAEBMDSEKFB-FXQIFTODSA-N Glu-Glu-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O CGOHAEBMDSEKFB-FXQIFTODSA-N 0.000 description 1
- CUXJIASLBRJOFV-LAEOZQHASA-N Glu-Gly-Ile Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(O)=O CUXJIASLBRJOFV-LAEOZQHASA-N 0.000 description 1
- VOORMNJKNBGYGK-YUMQZZPRSA-N Glu-Gly-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CCC(=O)O)N VOORMNJKNBGYGK-YUMQZZPRSA-N 0.000 description 1
- OPAINBJQDQTGJY-JGVFFNPUSA-N Glu-Gly-Pro Chemical compound C1C[C@@H](N(C1)C(=O)CNC(=O)[C@H](CCC(=O)O)N)C(=O)O OPAINBJQDQTGJY-JGVFFNPUSA-N 0.000 description 1
- VGOFRWOTSXVPAU-SDDRHHMPSA-N Glu-His-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CCC(=O)O)N)C(=O)O VGOFRWOTSXVPAU-SDDRHHMPSA-N 0.000 description 1
- IRXNJYPKBVERCW-DCAQKATOSA-N Glu-Leu-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O IRXNJYPKBVERCW-DCAQKATOSA-N 0.000 description 1
- OQXDUSZKISQQSS-GUBZILKMSA-N Glu-Lys-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O OQXDUSZKISQQSS-GUBZILKMSA-N 0.000 description 1
- YRMZCZIRHYCNHX-RYUDHWBXSA-N Glu-Phe-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)NCC(O)=O YRMZCZIRHYCNHX-RYUDHWBXSA-N 0.000 description 1
- CQGBSALYGOXQPE-HTUGSXCWSA-N Glu-Thr-Phe Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CCC(=O)O)N)O CQGBSALYGOXQPE-HTUGSXCWSA-N 0.000 description 1
- DLISPGXMKZTWQG-IFFSRLJSSA-N Glu-Thr-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O DLISPGXMKZTWQG-IFFSRLJSSA-N 0.000 description 1
- RXJFSLQVMGYQEL-IHRRRGAJSA-N Glu-Tyr-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(O)=O)CC1=CC=C(O)C=C1 RXJFSLQVMGYQEL-IHRRRGAJSA-N 0.000 description 1
- LZEUDRYSAZAJIO-AUTRQRHGSA-N Glu-Val-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O LZEUDRYSAZAJIO-AUTRQRHGSA-N 0.000 description 1
- FGGKGJHCVMYGCD-UKJIMTQDSA-N Glu-Val-Ile Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O FGGKGJHCVMYGCD-UKJIMTQDSA-N 0.000 description 1
- PYTZFYUXZZHOAD-WHFBIAKZSA-N Gly-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)CN PYTZFYUXZZHOAD-WHFBIAKZSA-N 0.000 description 1
- BRFJMRSRMOMIMU-WHFBIAKZSA-N Gly-Ala-Asn Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(O)=O BRFJMRSRMOMIMU-WHFBIAKZSA-N 0.000 description 1
- OGCIHJPYKVSMTE-YUMQZZPRSA-N Gly-Arg-Glu Chemical compound [H]NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O OGCIHJPYKVSMTE-YUMQZZPRSA-N 0.000 description 1
- GRIRDMVMJJDZKV-RCOVLWMOSA-N Gly-Asn-Val Chemical compound [H]NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O GRIRDMVMJJDZKV-RCOVLWMOSA-N 0.000 description 1
- QSTLUOIOYLYLLF-WDSKDSINSA-N Gly-Asp-Glu Chemical compound [H]NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O QSTLUOIOYLYLLF-WDSKDSINSA-N 0.000 description 1
- XBWMTPAIUQIWKA-BYULHYEWSA-N Gly-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CN XBWMTPAIUQIWKA-BYULHYEWSA-N 0.000 description 1
- GVVKYKCOFMMTKZ-WHFBIAKZSA-N Gly-Cys-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)CN GVVKYKCOFMMTKZ-WHFBIAKZSA-N 0.000 description 1
- LEGMTEAZGRRIMY-ZKWXMUAHSA-N Gly-Cys-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)CN LEGMTEAZGRRIMY-ZKWXMUAHSA-N 0.000 description 1
- HFXJIZNEXNIZIJ-BQBZGAKWSA-N Gly-Glu-Gln Chemical compound NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O HFXJIZNEXNIZIJ-BQBZGAKWSA-N 0.000 description 1
- YYPFZVIXAVDHIK-IUCAKERBSA-N Gly-Glu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CN YYPFZVIXAVDHIK-IUCAKERBSA-N 0.000 description 1
- NTOWAXLMQFKJPT-YUMQZZPRSA-N Gly-Glu-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)CN NTOWAXLMQFKJPT-YUMQZZPRSA-N 0.000 description 1
- JSNNHGHYGYMVCK-XVKPBYJWSA-N Gly-Glu-Val Chemical compound [H]NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O JSNNHGHYGYMVCK-XVKPBYJWSA-N 0.000 description 1
- GDOZQTNZPCUARW-YFKPBYRVSA-N Gly-Gly-Glu Chemical compound NCC(=O)NCC(=O)N[C@H](C(O)=O)CCC(O)=O GDOZQTNZPCUARW-YFKPBYRVSA-N 0.000 description 1
- QPCVIQJVRGXUSA-LURJTMIESA-N Gly-Gly-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)CNC(=O)CN QPCVIQJVRGXUSA-LURJTMIESA-N 0.000 description 1
- OLPPXYMMIARYAL-QMMMGPOBSA-N Gly-Gly-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)CNC(=O)CN OLPPXYMMIARYAL-QMMMGPOBSA-N 0.000 description 1
- SWQALSGKVLYKDT-ZKWXMUAHSA-N Gly-Ile-Ala Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O SWQALSGKVLYKDT-ZKWXMUAHSA-N 0.000 description 1
- SWQALSGKVLYKDT-UHFFFAOYSA-N Gly-Ile-Ala Natural products NCC(=O)NC(C(C)CC)C(=O)NC(C)C(O)=O SWQALSGKVLYKDT-UHFFFAOYSA-N 0.000 description 1
- HAXARWKYFIIHKD-ZKWXMUAHSA-N Gly-Ile-Ser Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O HAXARWKYFIIHKD-ZKWXMUAHSA-N 0.000 description 1
- COVXELOAORHTND-LSJOCFKGSA-N Gly-Ile-Val Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(O)=O COVXELOAORHTND-LSJOCFKGSA-N 0.000 description 1
- ULZCYBYDTUMHNF-IUCAKERBSA-N Gly-Leu-Glu Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O ULZCYBYDTUMHNF-IUCAKERBSA-N 0.000 description 1
- CCBIBMKQNXHNIN-ZETCQYMHSA-N Gly-Leu-Gly Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O CCBIBMKQNXHNIN-ZETCQYMHSA-N 0.000 description 1
- LRQXRHGQEVWGPV-NHCYSSNCSA-N Gly-Leu-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)CN LRQXRHGQEVWGPV-NHCYSSNCSA-N 0.000 description 1
- LHYJCVCQPWRMKZ-WEDXCCLWSA-N Gly-Leu-Thr Chemical compound [H]NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O LHYJCVCQPWRMKZ-WEDXCCLWSA-N 0.000 description 1
- VBOBNHSVQKKTOT-YUMQZZPRSA-N Gly-Lys-Ala Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O VBOBNHSVQKKTOT-YUMQZZPRSA-N 0.000 description 1
- PDUHNKAFQXQNLH-ZETCQYMHSA-N Gly-Lys-Gly Chemical compound NCCCC[C@H](NC(=O)CN)C(=O)NCC(O)=O PDUHNKAFQXQNLH-ZETCQYMHSA-N 0.000 description 1
- PTIIBFKSLCYQBO-NHCYSSNCSA-N Gly-Lys-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)CN PTIIBFKSLCYQBO-NHCYSSNCSA-N 0.000 description 1
- MHZXESQPPXOING-KBPBESRZSA-N Gly-Lys-Phe Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O MHZXESQPPXOING-KBPBESRZSA-N 0.000 description 1
- MXIULRKNFSCJHT-STQMWFEESA-N Gly-Phe-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CC=CC=C1 MXIULRKNFSCJHT-STQMWFEESA-N 0.000 description 1
- WNZOCXUOGVYYBJ-CDMKHQONSA-N Gly-Phe-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)CN)O WNZOCXUOGVYYBJ-CDMKHQONSA-N 0.000 description 1
- OOCFXNOVSLSHAB-IUCAKERBSA-N Gly-Pro-Pro Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 OOCFXNOVSLSHAB-IUCAKERBSA-N 0.000 description 1
- VNNRLUNBJSWZPF-ZKWXMUAHSA-N Gly-Ser-Ile Chemical compound [H]NCC(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O VNNRLUNBJSWZPF-ZKWXMUAHSA-N 0.000 description 1
- HQSKKSLNLSTONK-JTQLQIEISA-N Gly-Tyr-Gly Chemical compound OC(=O)CNC(=O)[C@@H](NC(=O)CN)CC1=CC=C(O)C=C1 HQSKKSLNLSTONK-JTQLQIEISA-N 0.000 description 1
- GWCJMBNBFYBQCV-XPUUQOCRSA-N Gly-Val-Ala Chemical compound NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O GWCJMBNBFYBQCV-XPUUQOCRSA-N 0.000 description 1
- RYAOJUMWLWUGNW-QMMMGPOBSA-N Gly-Val-Gly Chemical compound NCC(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O RYAOJUMWLWUGNW-QMMMGPOBSA-N 0.000 description 1
- BNMRSWQOHIQTFL-JSGCOSHPSA-N Gly-Val-Phe Chemical compound NCC(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 BNMRSWQOHIQTFL-JSGCOSHPSA-N 0.000 description 1
- YGHSQRJSHKYUJY-SCZZXKLOSA-N Gly-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)CN YGHSQRJSHKYUJY-SCZZXKLOSA-N 0.000 description 1
- 101100277701 Halobacterium salinarum gdhX gene Proteins 0.000 description 1
- JWTKVPMQCCRPQY-SRVKXCTJSA-N His-Asn-Leu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O JWTKVPMQCCRPQY-SRVKXCTJSA-N 0.000 description 1
- DFHVLUKTTVTCKY-PBCZWWQYSA-N His-Asn-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC1=CN=CN1)N)O DFHVLUKTTVTCKY-PBCZWWQYSA-N 0.000 description 1
- QNILDNVBIARMRK-XVYDVKMFSA-N His-Cys-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CC1=CN=CN1)N QNILDNVBIARMRK-XVYDVKMFSA-N 0.000 description 1
- VHHYJBSXXMPQGZ-AVGNSLFASA-N His-Gln-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC1=CN=CN1)N VHHYJBSXXMPQGZ-AVGNSLFASA-N 0.000 description 1
- YADRBUZBKHHDAO-XPUUQOCRSA-N His-Gly-Ala Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)NCC(=O)N[C@@H](C)C(O)=O YADRBUZBKHHDAO-XPUUQOCRSA-N 0.000 description 1
- FDQYIRHBVVUTJF-ZETCQYMHSA-N His-Gly-Gly Chemical compound [O-]C(=O)CNC(=O)CNC(=O)[C@@H]([NH3+])CC1=CN=CN1 FDQYIRHBVVUTJF-ZETCQYMHSA-N 0.000 description 1
- BDFCIKANUNMFGB-PMVVWTBXSA-N His-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC1=CN=CN1 BDFCIKANUNMFGB-PMVVWTBXSA-N 0.000 description 1
- KWBISLAEQZUYIC-UWJYBYFXSA-N His-His-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CC2=CN=CN2)N KWBISLAEQZUYIC-UWJYBYFXSA-N 0.000 description 1
- BILZDIPAKWZFSG-PYJNHQTQSA-N His-Ile-Met Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@H](CC1=CN=CN1)N BILZDIPAKWZFSG-PYJNHQTQSA-N 0.000 description 1
- IWXMHXYOACDSIA-PYJNHQTQSA-N His-Ile-Val Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(O)=O IWXMHXYOACDSIA-PYJNHQTQSA-N 0.000 description 1
- AIPUZFXMXAHZKY-QWRGUYRKSA-N His-Leu-Gly Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O AIPUZFXMXAHZKY-QWRGUYRKSA-N 0.000 description 1
- FLXCRBXJRJSDHX-AVGNSLFASA-N His-Pro-Val Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O FLXCRBXJRJSDHX-AVGNSLFASA-N 0.000 description 1
- NBWATNYAUVSAEQ-ZEILLAHLSA-N His-Thr-Thr Chemical compound C[C@H]([C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)O)NC(=O)[C@H](CC1=CN=CN1)N)O NBWATNYAUVSAEQ-ZEILLAHLSA-N 0.000 description 1
- WSXNWASHQNSMRX-GVXVVHGQSA-N His-Val-Gln Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CC1=CN=CN1)N WSXNWASHQNSMRX-GVXVVHGQSA-N 0.000 description 1
- XGBVLRJLHUVCNK-DCAQKATOSA-N His-Val-Ser Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O XGBVLRJLHUVCNK-DCAQKATOSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- VSZALHITQINTGC-GHCJXIJMSA-N Ile-Ala-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC(=O)O)C(=O)O)N VSZALHITQINTGC-GHCJXIJMSA-N 0.000 description 1
- VAXBXNPRXPHGHG-BJDJZHNGSA-N Ile-Ala-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)O)N VAXBXNPRXPHGHG-BJDJZHNGSA-N 0.000 description 1
- DMHGKBGOUAJRHU-UHFFFAOYSA-N Ile-Arg-Pro Natural products CCC(C)C(N)C(=O)NC(CCCN=C(N)N)C(=O)N1CCCC1C(O)=O DMHGKBGOUAJRHU-UHFFFAOYSA-N 0.000 description 1
- UKTUOMWSJPXODT-GUDRVLHUSA-N Ile-Asn-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N1CCC[C@@H]1C(=O)O)N UKTUOMWSJPXODT-GUDRVLHUSA-N 0.000 description 1
- RGSOCXHDOPQREB-ZPFDUUQYSA-N Ile-Asp-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)O)N RGSOCXHDOPQREB-ZPFDUUQYSA-N 0.000 description 1
- PFTFEWHJSAXGED-ZKWXMUAHSA-N Ile-Cys-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CS)C(=O)NCC(=O)O)N PFTFEWHJSAXGED-ZKWXMUAHSA-N 0.000 description 1
- CYHJCEKUMCNDFG-LAEOZQHASA-N Ile-Gln-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)NCC(=O)O)N CYHJCEKUMCNDFG-LAEOZQHASA-N 0.000 description 1
- DMZOUKXXHJQPTL-GRLWGSQLSA-N Ile-Gln-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)O)N DMZOUKXXHJQPTL-GRLWGSQLSA-N 0.000 description 1
- DVRDRICMWUSCBN-UKJIMTQDSA-N Ile-Gln-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](C(C)C)C(=O)O)N DVRDRICMWUSCBN-UKJIMTQDSA-N 0.000 description 1
- WZDCVAWMBUNDDY-KBIXCLLPSA-N Ile-Glu-Ala Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)O)N WZDCVAWMBUNDDY-KBIXCLLPSA-N 0.000 description 1
- KFVUBLZRFSVDGO-BYULHYEWSA-N Ile-Gly-Asp Chemical compound CC[C@H](C)[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC(O)=O KFVUBLZRFSVDGO-BYULHYEWSA-N 0.000 description 1
- GLLAUPMJCGKPFY-BLMTYFJBSA-N Ile-Ile-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)[C@@H](C)CC)C(O)=O)=CNC2=C1 GLLAUPMJCGKPFY-BLMTYFJBSA-N 0.000 description 1
- PKGGWLOLRLOPGK-XUXIUFHCSA-N Ile-Leu-Arg Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N PKGGWLOLRLOPGK-XUXIUFHCSA-N 0.000 description 1
- YGDWPQCLFJNMOL-MNXVOIDGSA-N Ile-Leu-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N YGDWPQCLFJNMOL-MNXVOIDGSA-N 0.000 description 1
- UIEZQYNXCYHMQS-BJDJZHNGSA-N Ile-Lys-Ala Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)O)N UIEZQYNXCYHMQS-BJDJZHNGSA-N 0.000 description 1
- IALVDKNUFSTICJ-GMOBBJLQSA-N Ile-Met-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(=O)O)C(=O)O)N IALVDKNUFSTICJ-GMOBBJLQSA-N 0.000 description 1
- UAELWXJFLZBKQS-WHOFXGATSA-N Ile-Phe-Gly Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](Cc1ccccc1)C(=O)NCC(O)=O UAELWXJFLZBKQS-WHOFXGATSA-N 0.000 description 1
- IVXJIMGDOYRLQU-XUXIUFHCSA-N Ile-Pro-Leu Chemical compound CC[C@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O IVXJIMGDOYRLQU-XUXIUFHCSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-UWTATZPHSA-N L-Alanine Natural products C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 229930195714 L-glutamate Natural products 0.000 description 1
- LHSGPCFBGJHPCY-UHFFFAOYSA-N L-leucine-L-tyrosine Natural products CC(C)CC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 LHSGPCFBGJHPCY-UHFFFAOYSA-N 0.000 description 1
- MJOZZTKJZQFKDK-GUBZILKMSA-N Leu-Ala-Gln Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCC(N)=O MJOZZTKJZQFKDK-GUBZILKMSA-N 0.000 description 1
- PBCHMHROGNUXMK-DLOVCJGASA-N Leu-Ala-His Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 PBCHMHROGNUXMK-DLOVCJGASA-N 0.000 description 1
- BQSLGJHIAGOZCD-CIUDSAMLSA-N Leu-Ala-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O BQSLGJHIAGOZCD-CIUDSAMLSA-N 0.000 description 1
- WGNOPSQMIQERPK-GARJFASQSA-N Leu-Asn-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N1CCC[C@@H]1C(=O)O)N WGNOPSQMIQERPK-GARJFASQSA-N 0.000 description 1
- WGNOPSQMIQERPK-UHFFFAOYSA-N Leu-Asn-Pro Natural products CC(C)CC(N)C(=O)NC(CC(=O)N)C(=O)N1CCCC1C(=O)O WGNOPSQMIQERPK-UHFFFAOYSA-N 0.000 description 1
- KTFHTMHHKXUYPW-ZPFDUUQYSA-N Leu-Asp-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O KTFHTMHHKXUYPW-ZPFDUUQYSA-N 0.000 description 1
- KAFOIVJDVSZUMD-UHFFFAOYSA-N Leu-Gln-Gln Natural products CC(C)CC(N)C(=O)NC(CCC(N)=O)C(=O)NC(CCC(N)=O)C(O)=O KAFOIVJDVSZUMD-UHFFFAOYSA-N 0.000 description 1
- GPICTNQYKHHHTH-GUBZILKMSA-N Leu-Gln-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O GPICTNQYKHHHTH-GUBZILKMSA-N 0.000 description 1
- KVMULWOHPPMHHE-DCAQKATOSA-N Leu-Glu-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O KVMULWOHPPMHHE-DCAQKATOSA-N 0.000 description 1
- OGUUKPXUTHOIAV-SDDRHHMPSA-N Leu-Glu-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N OGUUKPXUTHOIAV-SDDRHHMPSA-N 0.000 description 1
- WQWSMEOYXJTFRU-GUBZILKMSA-N Leu-Glu-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O WQWSMEOYXJTFRU-GUBZILKMSA-N 0.000 description 1
- ZFNLIDNJUWNIJL-WDCWCFNPSA-N Leu-Glu-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O ZFNLIDNJUWNIJL-WDCWCFNPSA-N 0.000 description 1
- OXRLYTYUXAQTHP-YUMQZZPRSA-N Leu-Gly-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(O)=O OXRLYTYUXAQTHP-YUMQZZPRSA-N 0.000 description 1
- QJUWBDPGGYVRHY-YUMQZZPRSA-N Leu-Gly-Cys Chemical compound CC(C)C[C@@H](C(=O)NCC(=O)N[C@@H](CS)C(=O)O)N QJUWBDPGGYVRHY-YUMQZZPRSA-N 0.000 description 1
- KEVYYIMVELOXCT-KBPBESRZSA-N Leu-Gly-Phe Chemical compound CC(C)C[C@H]([NH3+])C(=O)NCC(=O)N[C@H](C([O-])=O)CC1=CC=CC=C1 KEVYYIMVELOXCT-KBPBESRZSA-N 0.000 description 1
- JRJLGNFWYFSJHB-HOCLYGCPSA-N Leu-Gly-Trp Chemical compound [H]N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O JRJLGNFWYFSJHB-HOCLYGCPSA-N 0.000 description 1
- AVEGDIAXTDVBJS-XUXIUFHCSA-N Leu-Ile-Arg Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O AVEGDIAXTDVBJS-XUXIUFHCSA-N 0.000 description 1
- HGFGEMSVBMCFKK-MNXVOIDGSA-N Leu-Ile-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(O)=O HGFGEMSVBMCFKK-MNXVOIDGSA-N 0.000 description 1
- OMHLATXVNQSALM-FQUUOJAGSA-N Leu-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(C)C)N OMHLATXVNQSALM-FQUUOJAGSA-N 0.000 description 1
- PDQDCFBVYXEFSD-SRVKXCTJSA-N Leu-Leu-Asp Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O PDQDCFBVYXEFSD-SRVKXCTJSA-N 0.000 description 1
- JLWZLIQRYCTYBD-IHRRRGAJSA-N Leu-Lys-Arg Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O JLWZLIQRYCTYBD-IHRRRGAJSA-N 0.000 description 1
- QNTJIDXQHWUBKC-BZSNNMDCSA-N Leu-Lys-Phe Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O QNTJIDXQHWUBKC-BZSNNMDCSA-N 0.000 description 1
- GNRPTBRHRRZCMA-RWMBFGLXSA-N Leu-Met-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCSC)C(=O)N1CCC[C@@H]1C(=O)O)N GNRPTBRHRRZCMA-RWMBFGLXSA-N 0.000 description 1
- LQUIENKUVKPNIC-ULQDDVLXSA-N Leu-Met-Tyr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O LQUIENKUVKPNIC-ULQDDVLXSA-N 0.000 description 1
- ZDBMWELMUCLUPL-QEJZJMRPSA-N Leu-Phe-Ala Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C)C(O)=O)CC1=CC=CC=C1 ZDBMWELMUCLUPL-QEJZJMRPSA-N 0.000 description 1
- INCJJHQRZGQLFC-KBPBESRZSA-N Leu-Phe-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)NCC(O)=O INCJJHQRZGQLFC-KBPBESRZSA-N 0.000 description 1
- VULJUQZPSOASBZ-SRVKXCTJSA-N Leu-Pro-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O VULJUQZPSOASBZ-SRVKXCTJSA-N 0.000 description 1
- QONKWXNJRRNTBV-AVGNSLFASA-N Leu-Pro-Met Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCSC)C(=O)O)N QONKWXNJRRNTBV-AVGNSLFASA-N 0.000 description 1
- JDBQSGMJBMPNFT-AVGNSLFASA-N Leu-Pro-Val Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O JDBQSGMJBMPNFT-AVGNSLFASA-N 0.000 description 1
- KZZCOWMDDXDKSS-CIUDSAMLSA-N Leu-Ser-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O KZZCOWMDDXDKSS-CIUDSAMLSA-N 0.000 description 1
- MVHXGBZUJLWZOH-BJDJZHNGSA-N Leu-Ser-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O MVHXGBZUJLWZOH-BJDJZHNGSA-N 0.000 description 1
- IWMJFLJQHIDZQW-KKUMJFAQSA-N Leu-Ser-Phe Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 IWMJFLJQHIDZQW-KKUMJFAQSA-N 0.000 description 1
- ZJZNLRVCZWUONM-JXUBOQSCSA-N Leu-Thr-Ala Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O ZJZNLRVCZWUONM-JXUBOQSCSA-N 0.000 description 1
- GZRABTMNWJXFMH-UVOCVTCTSA-N Leu-Thr-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GZRABTMNWJXFMH-UVOCVTCTSA-N 0.000 description 1
- HOMFINRJHIIZNJ-HOCLYGCPSA-N Leu-Trp-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)NCC(O)=O HOMFINRJHIIZNJ-HOCLYGCPSA-N 0.000 description 1
- ARNIBBOXIAWUOP-MGHWNKPDSA-N Leu-Tyr-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O ARNIBBOXIAWUOP-MGHWNKPDSA-N 0.000 description 1
- TUIOUEWKFFVNLH-DCAQKATOSA-N Leu-Val-Cys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(O)=O TUIOUEWKFFVNLH-DCAQKATOSA-N 0.000 description 1
- QQXJROOJCMIHIV-AVGNSLFASA-N Leu-Val-Met Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCSC)C(O)=O QQXJROOJCMIHIV-AVGNSLFASA-N 0.000 description 1
- MSFITIBEMPWCBD-ULQDDVLXSA-N Leu-Val-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 MSFITIBEMPWCBD-ULQDDVLXSA-N 0.000 description 1
- FZIJIFCXUCZHOL-CIUDSAMLSA-N Lys-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCCN FZIJIFCXUCZHOL-CIUDSAMLSA-N 0.000 description 1
- PNPYKQFJGRFYJE-GUBZILKMSA-N Lys-Ala-Glu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O PNPYKQFJGRFYJE-GUBZILKMSA-N 0.000 description 1
- WSXTWLJHTLRFLW-SRVKXCTJSA-N Lys-Ala-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(O)=O WSXTWLJHTLRFLW-SRVKXCTJSA-N 0.000 description 1
- WQWZXKWOEVSGQM-DCAQKATOSA-N Lys-Ala-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCCN WQWZXKWOEVSGQM-DCAQKATOSA-N 0.000 description 1
- JGAMUXDWYSXYLM-SRVKXCTJSA-N Lys-Arg-Glu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O JGAMUXDWYSXYLM-SRVKXCTJSA-N 0.000 description 1
- DGAAQRAUOFHBFJ-CIUDSAMLSA-N Lys-Asn-Ala Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(O)=O DGAAQRAUOFHBFJ-CIUDSAMLSA-N 0.000 description 1
- SFQPJNQDUUYCLA-BJDJZHNGSA-N Lys-Cys-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CCCCN)N SFQPJNQDUUYCLA-BJDJZHNGSA-N 0.000 description 1
- RZHLIPMZXOEJTL-AVGNSLFASA-N Lys-Gln-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCCCN)N RZHLIPMZXOEJTL-AVGNSLFASA-N 0.000 description 1
- IMAKMJCBYCSMHM-AVGNSLFASA-N Lys-Glu-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCCN IMAKMJCBYCSMHM-AVGNSLFASA-N 0.000 description 1
- ITWQLSZTLBKWJM-YUMQZZPRSA-N Lys-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](N)CCCCN ITWQLSZTLBKWJM-YUMQZZPRSA-N 0.000 description 1
- ZXFRGTAIIZHNHG-AJNGGQMLSA-N Lys-Ile-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)O)NC(=O)[C@H](CCCCN)N ZXFRGTAIIZHNHG-AJNGGQMLSA-N 0.000 description 1
- SKRGVGLIRUGANF-AVGNSLFASA-N Lys-Leu-Glu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O SKRGVGLIRUGANF-AVGNSLFASA-N 0.000 description 1
- LMGNWHDWJDIOPK-DKIMLUQUSA-N Lys-Phe-Ile Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O LMGNWHDWJDIOPK-DKIMLUQUSA-N 0.000 description 1
- LUAJJLPHUXPQLH-KKUMJFAQSA-N Lys-Phe-Ser Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCCCN)N LUAJJLPHUXPQLH-KKUMJFAQSA-N 0.000 description 1
- HYSVGEAWTGPMOA-IHRRRGAJSA-N Lys-Pro-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O HYSVGEAWTGPMOA-IHRRRGAJSA-N 0.000 description 1
- JMNRXRPBHFGXQX-GUBZILKMSA-N Lys-Ser-Glu Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O JMNRXRPBHFGXQX-GUBZILKMSA-N 0.000 description 1
- MDDUIRLQCYVRDO-NHCYSSNCSA-N Lys-Val-Asn Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCCCN MDDUIRLQCYVRDO-NHCYSSNCSA-N 0.000 description 1
- QLFAPXUXEBAWEK-NHCYSSNCSA-N Lys-Val-Asp Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O QLFAPXUXEBAWEK-NHCYSSNCSA-N 0.000 description 1
- JQECLVNLAZGHRQ-CIUDSAMLSA-N Met-Asp-Gln Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCC(N)=O JQECLVNLAZGHRQ-CIUDSAMLSA-N 0.000 description 1
- LQMHZERGCQJKAH-STQMWFEESA-N Met-Gly-Phe Chemical compound CSCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 LQMHZERGCQJKAH-STQMWFEESA-N 0.000 description 1
- MVBZBRKNZVJEKK-DTWKUNHWSA-N Met-Gly-Pro Chemical compound CSCC[C@@H](C(=O)NCC(=O)N1CCC[C@@H]1C(=O)O)N MVBZBRKNZVJEKK-DTWKUNHWSA-N 0.000 description 1
- SXWQMBGNFXAGAT-FJXKBIBVSA-N Met-Gly-Thr Chemical compound CSCC[C@H](N)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(O)=O SXWQMBGNFXAGAT-FJXKBIBVSA-N 0.000 description 1
- HAQLBBVZAGMESV-IHRRRGAJSA-N Met-Lys-Lys Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(O)=O HAQLBBVZAGMESV-IHRRRGAJSA-N 0.000 description 1
- LUYURUYVNYGKGM-RCWTZXSCSA-N Met-Pro-Thr Chemical compound CSCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O LUYURUYVNYGKGM-RCWTZXSCSA-N 0.000 description 1
- FXBKQTOGURNXSL-HJGDQZAQSA-N Met-Thr-Glu Chemical compound CSCC[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CCC(O)=O FXBKQTOGURNXSL-HJGDQZAQSA-N 0.000 description 1
- WUGMRIBZSVSJNP-UHFFFAOYSA-N N-L-alanyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)C(N)C)C(O)=O)=CNC2=C1 WUGMRIBZSVSJNP-UHFFFAOYSA-N 0.000 description 1
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 1
- AJHCSUXXECOXOY-UHFFFAOYSA-N N-glycyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)CN)C(O)=O)=CNC2=C1 AJHCSUXXECOXOY-UHFFFAOYSA-N 0.000 description 1
- ACFIXJIJDZMPPO-NNYOXOHSSA-N NADPH Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](OP(O)(O)=O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 ACFIXJIJDZMPPO-NNYOXOHSSA-N 0.000 description 1
- BQVUABVGYYSDCJ-UHFFFAOYSA-N Nalpha-L-Leucyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)C(N)CC(C)C)C(O)=O)=CNC2=C1 BQVUABVGYYSDCJ-UHFFFAOYSA-N 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- ULECEJGNDHWSKD-QEJZJMRPSA-N Phe-Ala-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=CC=C1 ULECEJGNDHWSKD-QEJZJMRPSA-N 0.000 description 1
- ZWJKVFAYPLPCQB-UNQGMJICSA-N Phe-Arg-Thr Chemical compound C[C@@H](O)[C@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)Cc1ccccc1)C(O)=O ZWJKVFAYPLPCQB-UNQGMJICSA-N 0.000 description 1
- LJUUGSWZPQOJKD-JYJNAYRXSA-N Phe-Arg-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](N)Cc1ccccc1)C(O)=O LJUUGSWZPQOJKD-JYJNAYRXSA-N 0.000 description 1
- IILUKIJNFMUBNF-IHRRRGAJSA-N Phe-Gln-Gln Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O IILUKIJNFMUBNF-IHRRRGAJSA-N 0.000 description 1
- KAGCQPSEVAETCA-JYJNAYRXSA-N Phe-Gln-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC1=CC=CC=C1)N KAGCQPSEVAETCA-JYJNAYRXSA-N 0.000 description 1
- BEEVXUYVEHXWRQ-YESZJQIVSA-N Phe-His-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CC3=CC=CC=C3)N)C(=O)O BEEVXUYVEHXWRQ-YESZJQIVSA-N 0.000 description 1
- KBVJZCVLQWCJQN-KKUMJFAQSA-N Phe-Leu-Asn Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O KBVJZCVLQWCJQN-KKUMJFAQSA-N 0.000 description 1
- WWPAHTZOWURIMR-ULQDDVLXSA-N Phe-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CC1=CC=CC=C1 WWPAHTZOWURIMR-ULQDDVLXSA-N 0.000 description 1
- MCIXMYKSPQUMJG-SRVKXCTJSA-N Phe-Ser-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O MCIXMYKSPQUMJG-SRVKXCTJSA-N 0.000 description 1
- XNQMZHLAYFWSGJ-HTUGSXCWSA-N Phe-Thr-Glu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O XNQMZHLAYFWSGJ-HTUGSXCWSA-N 0.000 description 1
- VGTJSEYTVMAASM-RPTUDFQQSA-N Phe-Thr-Tyr Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O VGTJSEYTVMAASM-RPTUDFQQSA-N 0.000 description 1
- BQMFWUKNOCJDNV-HJWJTTGWSA-N Phe-Val-Ile Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O BQMFWUKNOCJDNV-HJWJTTGWSA-N 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 101100392454 Picrophilus torridus (strain ATCC 700027 / DSM 9790 / JCM 10055 / NBRC 100828) gdh2 gene Proteins 0.000 description 1
- HAEGAELAYWSUNC-WPRPVWTQSA-N Pro-Gly-Val Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O HAEGAELAYWSUNC-WPRPVWTQSA-N 0.000 description 1
- STASJMBVVHNWCG-IHRRRGAJSA-N Pro-His-Leu Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C([O-])=O)NC(=O)[C@H]1[NH2+]CCC1)C1=CN=CN1 STASJMBVVHNWCG-IHRRRGAJSA-N 0.000 description 1
- HFNPOYOKIPGAEI-SRVKXCTJSA-N Pro-Leu-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1 HFNPOYOKIPGAEI-SRVKXCTJSA-N 0.000 description 1
- ABSSTGUCBCDKMU-UWVGGRQHSA-N Pro-Lys-Gly Chemical compound NCCCC[C@@H](C(=O)NCC(O)=O)NC(=O)[C@@H]1CCCN1 ABSSTGUCBCDKMU-UWVGGRQHSA-N 0.000 description 1
- ZJXXCGZFYQQETF-CYDGBPFRSA-N Pro-Met-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@@H]1CCCN1 ZJXXCGZFYQQETF-CYDGBPFRSA-N 0.000 description 1
- GFHXZNVJIKMAGO-IHRRRGAJSA-N Pro-Phe-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O GFHXZNVJIKMAGO-IHRRRGAJSA-N 0.000 description 1
- RCYUBVHMVUHEBM-RCWTZXSCSA-N Pro-Pro-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O RCYUBVHMVUHEBM-RCWTZXSCSA-N 0.000 description 1
- GMJDSFYVTAMIBF-FXQIFTODSA-N Pro-Ser-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O GMJDSFYVTAMIBF-FXQIFTODSA-N 0.000 description 1
- KWMZPPWYBVZIER-XGEHTFHBSA-N Pro-Ser-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KWMZPPWYBVZIER-XGEHTFHBSA-N 0.000 description 1
- UIUWGMRJTWHIJZ-ULQDDVLXSA-N Pro-Tyr-Lys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)N[C@@H](CCCCN)C(=O)O UIUWGMRJTWHIJZ-ULQDDVLXSA-N 0.000 description 1
- OOZJHTXCLJUODH-QXEWZRGKSA-N Pro-Val-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]1CCCN1 OOZJHTXCLJUODH-QXEWZRGKSA-N 0.000 description 1
- 101100116769 Saccharolobus solfataricus (strain ATCC 35092 / DSM 1617 / JCM 11322 / P2) gdhA-2 gene Proteins 0.000 description 1
- SRTCFKGBYBZRHA-ACZMJKKPSA-N Ser-Ala-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O SRTCFKGBYBZRHA-ACZMJKKPSA-N 0.000 description 1
- HQTKVSCNCDLXSX-BQBZGAKWSA-N Ser-Arg-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O HQTKVSCNCDLXSX-BQBZGAKWSA-N 0.000 description 1
- HBOABDXGTMMDSE-GUBZILKMSA-N Ser-Arg-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(O)=O HBOABDXGTMMDSE-GUBZILKMSA-N 0.000 description 1
- OJPHFSOMBZKQKQ-GUBZILKMSA-N Ser-Gln-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CO OJPHFSOMBZKQKQ-GUBZILKMSA-N 0.000 description 1
- MIJWOJAXARLEHA-WDSKDSINSA-N Ser-Gly-Glu Chemical compound OC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(O)=O MIJWOJAXARLEHA-WDSKDSINSA-N 0.000 description 1
- YMTLKLXDFCSCNX-BYPYZUCNSA-N Ser-Gly-Gly Chemical compound OC[C@H](N)C(=O)NCC(=O)NCC(O)=O YMTLKLXDFCSCNX-BYPYZUCNSA-N 0.000 description 1
- UIGMAMGZOJVTDN-WHFBIAKZSA-N Ser-Gly-Ser Chemical compound OC[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O UIGMAMGZOJVTDN-WHFBIAKZSA-N 0.000 description 1
- CXBFHZLODKPIJY-AAEUAGOBSA-N Ser-Gly-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CO)N CXBFHZLODKPIJY-AAEUAGOBSA-N 0.000 description 1
- YUJLIIRMIAGMCQ-CIUDSAMLSA-N Ser-Leu-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YUJLIIRMIAGMCQ-CIUDSAMLSA-N 0.000 description 1
- SRSPTFBENMJHMR-WHFBIAKZSA-N Ser-Ser-Gly Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O SRSPTFBENMJHMR-WHFBIAKZSA-N 0.000 description 1
- XQJCEKXQUJQNNK-ZLUOBGJFSA-N Ser-Ser-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O XQJCEKXQUJQNNK-ZLUOBGJFSA-N 0.000 description 1
- XJDMUQCLVSCRSJ-VZFHVOOUSA-N Ser-Thr-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O XJDMUQCLVSCRSJ-VZFHVOOUSA-N 0.000 description 1
- VLMIUSLQONKLDV-HEIBUPTGSA-N Ser-Thr-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O VLMIUSLQONKLDV-HEIBUPTGSA-N 0.000 description 1
- PCMZJFMUYWIERL-ZKWXMUAHSA-N Ser-Val-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O PCMZJFMUYWIERL-ZKWXMUAHSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- MQBTXMPQNCGSSZ-OSUNSFLBSA-N Thr-Arg-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)[C@@H](C)O)CCCN=C(N)N MQBTXMPQNCGSSZ-OSUNSFLBSA-N 0.000 description 1
- JVTHIXKSVYEWNI-JRQIVUDYSA-N Thr-Asn-Tyr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O JVTHIXKSVYEWNI-JRQIVUDYSA-N 0.000 description 1
- FHDLKMFZKRUQCE-HJGDQZAQSA-N Thr-Glu-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O FHDLKMFZKRUQCE-HJGDQZAQSA-N 0.000 description 1
- LHEZGZQRLDBSRR-WDCWCFNPSA-N Thr-Glu-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O LHEZGZQRLDBSRR-WDCWCFNPSA-N 0.000 description 1
- KBLYJPQSNGTDIU-LOKLDPHHSA-N Thr-Glu-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N)O KBLYJPQSNGTDIU-LOKLDPHHSA-N 0.000 description 1
- XFTYVCHLARBHBQ-FOHZUACHSA-N Thr-Gly-Asn Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O XFTYVCHLARBHBQ-FOHZUACHSA-N 0.000 description 1
- WBCCCPZIJIJTSD-TUBUOCAGSA-N Thr-His-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H]([C@@H](C)O)N WBCCCPZIJIJTSD-TUBUOCAGSA-N 0.000 description 1
- AYCQVUUPIJHJTA-IXOXFDKPSA-N Thr-His-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(O)=O AYCQVUUPIJHJTA-IXOXFDKPSA-N 0.000 description 1
- DDDLIMCZFKOERC-SVSWQMSJSA-N Thr-Ile-Cys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H]([C@@H](C)O)N DDDLIMCZFKOERC-SVSWQMSJSA-N 0.000 description 1
- VRUFCJZQDACGLH-UVOCVTCTSA-N Thr-Leu-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O VRUFCJZQDACGLH-UVOCVTCTSA-N 0.000 description 1
- KKPOGALELPLJTL-MEYUZBJRSA-N Thr-Lys-Tyr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 KKPOGALELPLJTL-MEYUZBJRSA-N 0.000 description 1
- MROIJTGJGIDEEJ-RCWTZXSCSA-N Thr-Pro-Pro Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 MROIJTGJGIDEEJ-RCWTZXSCSA-N 0.000 description 1
- BBPCSGKKPJUYRB-UVOCVTCTSA-N Thr-Thr-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O BBPCSGKKPJUYRB-UVOCVTCTSA-N 0.000 description 1
- VYVBSMCZNHOZGD-RCWTZXSCSA-N Thr-Val-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(O)=O VYVBSMCZNHOZGD-RCWTZXSCSA-N 0.000 description 1
- KVMZNMYZCKORIG-UBHSHLNASA-N Trp-Cys-Asp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)O)C(=O)O)N KVMZNMYZCKORIG-UBHSHLNASA-N 0.000 description 1
- NLWCSMOXNKBRLC-WDSOQIARSA-N Trp-Lys-Val Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O NLWCSMOXNKBRLC-WDSOQIARSA-N 0.000 description 1
- WMIUTJPFHMMUGY-ZFWWWQNUSA-N Trp-Pro-Gly Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CC2=CNC3=CC=CC=C32)N)C(=O)NCC(=O)O WMIUTJPFHMMUGY-ZFWWWQNUSA-N 0.000 description 1
- GFUOTIPYXKAPAH-BVSLBCMMSA-N Trp-Pro-Phe Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O GFUOTIPYXKAPAH-BVSLBCMMSA-N 0.000 description 1
- BOBZBMOTRORUPT-XIRDDKMYSA-N Trp-Ser-Leu Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O)=CNC2=C1 BOBZBMOTRORUPT-XIRDDKMYSA-N 0.000 description 1
- HKIUVWMZYFBIHG-KKUMJFAQSA-N Tyr-Arg-Gln Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N)O HKIUVWMZYFBIHG-KKUMJFAQSA-N 0.000 description 1
- AKXBNSZMYAOGLS-STQMWFEESA-N Tyr-Arg-Gly Chemical compound NC(N)=NCCC[C@@H](C(=O)NCC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 AKXBNSZMYAOGLS-STQMWFEESA-N 0.000 description 1
- YMUQBRQQCPQEQN-CXTHYWKRSA-N Tyr-Ile-Tyr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)N YMUQBRQQCPQEQN-CXTHYWKRSA-N 0.000 description 1
- UEOOXDLMQZBPFR-ZKWXMUAHSA-N Val-Ala-Asn Chemical compound C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](C(C)C)N UEOOXDLMQZBPFR-ZKWXMUAHSA-N 0.000 description 1
- FZSPNKUFROZBSG-ZKWXMUAHSA-N Val-Ala-Asp Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC(O)=O FZSPNKUFROZBSG-ZKWXMUAHSA-N 0.000 description 1
- ZLFHAAGHGQBQQN-GUBZILKMSA-N Val-Ala-Pro Natural products CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O ZLFHAAGHGQBQQN-GUBZILKMSA-N 0.000 description 1
- KKHRWGYHBZORMQ-NHCYSSNCSA-N Val-Arg-Glu Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N KKHRWGYHBZORMQ-NHCYSSNCSA-N 0.000 description 1
- DNOOLPROHJWCSQ-RCWTZXSCSA-N Val-Arg-Thr Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O DNOOLPROHJWCSQ-RCWTZXSCSA-N 0.000 description 1
- CGGVNFJRZJUVAE-BYULHYEWSA-N Val-Asp-Asn Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N CGGVNFJRZJUVAE-BYULHYEWSA-N 0.000 description 1
- HZYOWMGWKKRMBZ-BYULHYEWSA-N Val-Asp-Asp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)O)N HZYOWMGWKKRMBZ-BYULHYEWSA-N 0.000 description 1
- FRUYSSRPJXNRRB-GUBZILKMSA-N Val-Cys-Arg Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N FRUYSSRPJXNRRB-GUBZILKMSA-N 0.000 description 1
- FBVUOEYVGNMRMD-NAKRPEOUSA-N Val-Cys-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](C(C)C)N FBVUOEYVGNMRMD-NAKRPEOUSA-N 0.000 description 1
- QHFQQRKNGCXTHL-AUTRQRHGSA-N Val-Gln-Glu Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O QHFQQRKNGCXTHL-AUTRQRHGSA-N 0.000 description 1
- XEYUMGGWQCIWAR-XVKPBYJWSA-N Val-Gln-Gly Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)NCC(=O)O)N XEYUMGGWQCIWAR-XVKPBYJWSA-N 0.000 description 1
- MHAHQDBEIDPFQS-NHCYSSNCSA-N Val-Glu-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)C(C)C MHAHQDBEIDPFQS-NHCYSSNCSA-N 0.000 description 1
- DJEVQCWNMQOABE-RCOVLWMOSA-N Val-Gly-Asp Chemical compound CC(C)[C@@H](C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)O)N DJEVQCWNMQOABE-RCOVLWMOSA-N 0.000 description 1
- KDKLLPMFFGYQJD-CYDGBPFRSA-N Val-Ile-Arg Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](C(C)C)N KDKLLPMFFGYQJD-CYDGBPFRSA-N 0.000 description 1
- APQIVBCUIUDSMB-OSUNSFLBSA-N Val-Ile-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)O)NC(=O)[C@H](C(C)C)N APQIVBCUIUDSMB-OSUNSFLBSA-N 0.000 description 1
- DJQIUOKSNRBTSV-CYDGBPFRSA-N Val-Ile-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)O)NC(=O)[C@H](C(C)C)N DJQIUOKSNRBTSV-CYDGBPFRSA-N 0.000 description 1
- AGXGCFSECFQMKB-NHCYSSNCSA-N Val-Leu-Asp Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](C(C)C)N AGXGCFSECFQMKB-NHCYSSNCSA-N 0.000 description 1
- XTDDIVQWDXMRJL-IHRRRGAJSA-N Val-Leu-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](C(C)C)N XTDDIVQWDXMRJL-IHRRRGAJSA-N 0.000 description 1
- AEMPCGRFEZTWIF-IHRRRGAJSA-N Val-Leu-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(O)=O AEMPCGRFEZTWIF-IHRRRGAJSA-N 0.000 description 1
- RWOGENDAOGMHLX-DCAQKATOSA-N Val-Lys-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C(C)C)N RWOGENDAOGMHLX-DCAQKATOSA-N 0.000 description 1
- RSGHLMMKXJGCMK-JYJNAYRXSA-N Val-Met-Phe Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)N RSGHLMMKXJGCMK-JYJNAYRXSA-N 0.000 description 1
- WSUWDIVCPOJFCX-TUAOUCFPSA-N Val-Met-Pro Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)N1CCC[C@@H]1C(=O)O)N WSUWDIVCPOJFCX-TUAOUCFPSA-N 0.000 description 1
- YKNOJPJWNVHORX-UNQGMJICSA-N Val-Phe-Thr Chemical compound CC(C)[C@H](N)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)O)C(O)=O)CC1=CC=CC=C1 YKNOJPJWNVHORX-UNQGMJICSA-N 0.000 description 1
- XBJKAZATRJBDCU-GUBZILKMSA-N Val-Pro-Ala Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O XBJKAZATRJBDCU-GUBZILKMSA-N 0.000 description 1
- YTNGABPUXFEOGU-SRVKXCTJSA-N Val-Pro-Arg Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(O)=O YTNGABPUXFEOGU-SRVKXCTJSA-N 0.000 description 1
- UGFMVXRXULGLNO-XPUUQOCRSA-N Val-Ser-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O UGFMVXRXULGLNO-XPUUQOCRSA-N 0.000 description 1
- TVGWMCTYUFBXAP-QTKMDUPCSA-N Val-Thr-His Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](C(C)C)N)O TVGWMCTYUFBXAP-QTKMDUPCSA-N 0.000 description 1
- WHNSHJJNWNSTSU-BZSNNMDCSA-N Val-Val-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)C(C)C)C(O)=O)=CNC2=C1 WHNSHJJNWNSTSU-BZSNNMDCSA-N 0.000 description 1
- FZNCGRZWXLXZSZ-CIQUZCHMSA-N Voglibose Chemical compound OCC(CO)N[C@H]1C[C@](O)(CO)[C@@H](O)[C@H](O)[C@H]1O FZNCGRZWXLXZSZ-CIQUZCHMSA-N 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 229960003767 alanine Drugs 0.000 description 1
- 108010076324 alanyl-glycyl-glycine Proteins 0.000 description 1
- 108010024078 alanyl-glycyl-serine Proteins 0.000 description 1
- 108010086434 alanyl-seryl-glycine Proteins 0.000 description 1
- 108010005233 alanylglutamic acid Proteins 0.000 description 1
- 108010011559 alanylphenylalanine Proteins 0.000 description 1
- 108010087924 alanylproline Proteins 0.000 description 1
- QDJFZWFIWGSPEC-UHFFFAOYSA-N alumane;rhodium Chemical compound [AlH3].[Rh] QDJFZWFIWGSPEC-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 108010013835 arginine glutamate Proteins 0.000 description 1
- 108010009111 arginyl-glycyl-glutamic acid Proteins 0.000 description 1
- 108010043240 arginyl-leucyl-glycine Proteins 0.000 description 1
- 108010062796 arginyllysine Proteins 0.000 description 1
- 108010060035 arginylproline Proteins 0.000 description 1
- 108010010430 asparagine-proline-alanine Proteins 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 108010093581 aspartyl-proline Proteins 0.000 description 1
- 108010047857 aspartylglycine Proteins 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000013064 chemical raw material Substances 0.000 description 1
- 231100000481 chemical toxicant Toxicity 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 108010054813 diprotin B Proteins 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- KKGQTZUTZRNORY-UHFFFAOYSA-N fingolimod Chemical compound CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1 KKGQTZUTZRNORY-UHFFFAOYSA-N 0.000 description 1
- 229960000556 fingolimod Drugs 0.000 description 1
- 229940049906 glutamate Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 108010049041 glutamylalanine Proteins 0.000 description 1
- 108010079547 glutamylmethionine Proteins 0.000 description 1
- 108010062266 glycyl-glycyl-argininal Proteins 0.000 description 1
- 108010051307 glycyl-glycyl-proline Proteins 0.000 description 1
- 108010074027 glycyl-seryl-phenylalanine Proteins 0.000 description 1
- 108010089804 glycyl-threonine Proteins 0.000 description 1
- 108010010147 glycylglutamine Proteins 0.000 description 1
- 108010081551 glycylphenylalanine Proteins 0.000 description 1
- 108010077515 glycylproline Proteins 0.000 description 1
- 108010036413 histidylglycine Proteins 0.000 description 1
- 108010028295 histidylhistidine Proteins 0.000 description 1
- 108010025306 histidylleucine Proteins 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 108010051673 leucyl-glycyl-phenylalanine Proteins 0.000 description 1
- 108010012058 leucyltyrosine Proteins 0.000 description 1
- 108010025153 lysyl-alanyl-alanine Proteins 0.000 description 1
- 108010072591 lysyl-leucyl-alanyl-arginine Proteins 0.000 description 1
- 238000012269 metabolic engineering Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 108010063431 methionyl-aspartyl-glycine Proteins 0.000 description 1
- 108010056582 methionylglutamic acid Proteins 0.000 description 1
- 108010085203 methionylmethionine Proteins 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 108010074082 phenylalanyl-alanyl-lysine Proteins 0.000 description 1
- 108010012581 phenylalanylglutamate Proteins 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 108010031719 prolyl-serine Proteins 0.000 description 1
- 108010004914 prolylarginine Proteins 0.000 description 1
- 108010070643 prolylglutamic acid Proteins 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 108010026333 seryl-proline Proteins 0.000 description 1
- 108010071207 serylmethionine Proteins 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 108010031491 threonyl-lysyl-glutamic acid Proteins 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 108700004896 tripeptide FEG Proteins 0.000 description 1
- 108010038745 tryptophylglycine Proteins 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 108010051110 tyrosyl-lysine Proteins 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 229960001729 voglibose Drugs 0.000 description 1
Images
Classifications
-
- 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
- C12P13/00—Preparation of nitrogen-containing organic compounds
- C12P13/001—Amines; Imines
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/10—Transferases (2.)
- C12N9/1096—Transferases (2.) transferring nitrogenous groups (2.6)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y206/00—Transferases transferring nitrogenous groups (2.6)
- C12Y206/01—Transaminases (2.6.1)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
本发明提供了一种高效制备2‑氨基‑1,3‑丙二醇的微生物发酵法。具体地,本发明设计和构建了2‑氨基‑1,3‑丙二醇的人工生物合成途径,并成功构建了生物合成2‑氨基‑1,3‑丙二醇的重组基因工程菌株。本发明利用蛋白质工程技术首次获得具有磷酸二羟基丙酮氨基转移酶单一活性的融合工程蛋白。经代谢途径系统优化,首次获得了生物合成途径明确且运行高效稳定的人工生物合成途径,建立了利用简单碳源一步发酵高效稳定合成2‑氨基‑1,3‑丙二醇的重组工程菌株和发酵工艺过程,为大规模生物发酵法高效制备2‑氨基‑1,3‑丙二醇奠定了催化元件、合成途径和菌株系统等的基础。
Description
技术领域
本发明涉及生物技术工程领域,具体地,涉及一种构建重组工程菌株LYC-5的方法及其应用于化合物2-氨基-1,3-丙二醇的生物制造。
背景技术
2-氨基-1,3-丙二醇是一种重要的化工原料。在医药化工领域中,2-氨基-1,3-丙二醇是化学合成新一代非离子型造影剂碘帕醇(iopamidol)、二型糖尿病治疗药物伏格列波糖、多发性硬化治疗药物芬戈莫德以及抗生素氯霉素等药物的重要前体。
目前,2-氨基-1,3-丙二醇的生产主要依赖化学合成反应工艺。迄今为止,在化学法合成2-氨基-1,3-丙二醇的研究领域已取得一些进展。例如,美国专利(4448999)利用2-硝基-1,3-丙二醇钠盐作为原料,在甲醇溶液中进行催化氢化反应合成丝氨醇;美国专利(5922917)公开了以1,3-二羟丙酮肟作为原料,以铑铝催化剂进行催化氢化合成2-氨基-1,3-丙二醇;美国专利(4978793)公开了以硝基甲烷作为原料,转化为中间体5-硝基-1,3-二氧六环,再进一步反应生成产物2-氨基-1,3-丙二醇;中国专利CN1948272A公开了以钯/碳作为催化剂,利用水合肼将原料2-硝基-1,3-丙二醇钠盐在常压下还原制备2-氨基-1,3-丙二醇;中国专利CN103508905A公布了以硝基甲烷和多聚甲醛为原料,氢气为还原剂,钯/碳为催化剂制备丝氨醇的合成路线;中国专利CN102731324A公布了以5-硝基-2,2-二甲基-1,3-二氧六烷为原料,水合肼为还原剂还原底物,再经酸水解去掉保护基团而获得最终产物2-氨基-1,3-丙二醇。
前述系列化学合成工艺虽然已经广泛应用于2-氨基-1,3-丙二醇的生产,但是存在如下缺点。上述2-氨基-1,3-丙二醇的化学合成方法所用的底物大多数都是来源于化石原料,而且具有爆炸性,故合成反应过程具有一定的危险性;化学合成反应需要用到昂贵的金属催化剂,反应体系中的钠盐易覆盖在催化剂表面进而使催化剂失活,最终导致2-氨基-1,3-丙二醇的收率低和副产物的产生,产品纯度不理想。
化石原料是不可再生资源,为了减少对化石原料的依赖和对环境的污染和压力,迫切需要改变现有的生产方式。近年来随着合成生物学的发展,构建微生物细胞工厂利用可再生资源作为原料实现高附加值化合物的微生物制造是一个有效的替代途径,以减少化学品制造业发展对环境和资源的依赖。
然而,迄今为止,利用生物法制备重要化学中间体2-氨基-1,3-丙二醇的报道较少。鉴于上述存在的诸多问题,目前2-氨基-1,3-丙二醇的生物法制备仍然面对巨大的挑战,极大地限制了其工业化应用。
因此,本领域迫切需要开发一种稳定环保高效的2-氨基-1,3-丙二醇生物制备法。
发明内容
本发明的目的就是提供一种稳定高产2-氨基-1,3-丙二醇的生物制法,即设计构建2-氨基-1,3-丙二醇的人工生物合成途径,综合利用合成生物学和代谢工程技术构建高效合成2-氨基-1,3-丙二醇的重组微生物细胞工厂,实现利用简单碳源稳定高效合成和制备2-氨基-1,3-丙二醇。
在本发明的第一方面,提供了一种生产2-氨基-1,3-丙二醇的方法,包括步骤:
(a)在适合发酵的条件下,培养工程菌,从而产生2-氨基-1,3-丙二醇;
(b)任选地从发酵产物中分离2-氨基-1,3-丙二醇;
所述工程菌具有以下特征:
(i)表达外源的磷酸二羟基丙酮氨基转移酶;和
(ii)任选地具有增强活性的谷氨酸脱氢酶;
(iii)任选地具有增强活性的磷酸丝氨酸磷酸酶;
并且,所述发酵条件中,无甘油。
在另一优选例中,所述工程菌为经改造的受体菌株,所述受体菌株选自下组:原核生物或真核生物。
在另一优选例中,所述受体菌株选自下组:大肠杆菌属(Escherichia coli)、蓝细菌、酵母菌等,或其组合。
在另一优选例中,所述受体菌株为大肠杆菌HMS174(DE3)。
在另一优选例中,所述受体菌株的载体质粒中包括抗性基因元件。
在另一优选例中,所述抗性包括:抗氨苄青霉素、抗卡那霉素、抗氯霉素,抗链霉素,或其组合。
在另一优选例中,所述外源的磷酸二羟基丙酮氨基转移酶为一融合蛋白,所述融合蛋白的氨基酸序列从N端到C端的构成如式I所示:
A-B 式I
其中,
组件A是一种蛋白功能增强分子部分的序列;
组件B是野生型磷酸二羟基丙酮氨基转移酶/二羟根瘤毒素合酶及其N端的片段序列。
在另一优选例中,所述组件A的氨基酸序列如SEQ ID NO:2所示。
在另一优选例中,所述组件B中,所述野生型磷酸二羟基丙酮氨基转移酶/二羟根瘤毒素合酶的来源包括:埃氏慢生根瘤菌、大豆根瘤菌、花生根瘤菌、中华根瘤菌,或其组合。
在另一优选例中,所述野生型磷酸二羟基丙酮氨基转移酶/二羟根瘤毒素合酶的序列包括:天然序列、人工合成序列,或其组合。
在另一优选例中,所述野生型磷酸二羟基丙酮氨基转移酶/二羟根瘤毒素合酶具有催化磷酸二羟基丙酮转氨生成2-氨基-1,3-丙二醇磷酸的活性。
在另一优选例中,所述野生型磷酸二羟基丙酮氨基转移酶/二羟根瘤毒素合酶还包括将其氨基酸序列中的一个或多个氨基酸残基进行取代、C-端序列的缺失或添加而形成,且具有催化磷酸二羟基丙酮转氨生成2-氨基-1,3-丙二醇磷酸的活性的蛋白。
在另一优选例中,所述野生型磷酸二羟基丙酮氨基转移酶/二羟根瘤毒素合酶的来源还包括与磷酸二羟基丙酮氨基转移酶具备同种功能的酶。
在另一优选例中,所述同种功能的酶具备催化磷酸二羟基丙酮以L-谷氨酸、L-天冬氨酸或者L-丙氨酸等提供氨基供体发生转氨反应生成2-氨基-1,3-丙二醇磷酸的功能。
在另一优选例中,所述同种功能的酶的来源包括:埃氏慢生根瘤菌、大豆根瘤菌、花生根瘤菌、中华根瘤菌,或其组合。
在另一优选例中,所述野生型磷酸二羟基丙酮氨基转移酶/二羟根瘤毒素合酶的氨基酸序列如SEQ ID NO:1所示。
在另一优选例中,所述组件B为所述野生型磷酸二羟基丙酮氨基转移酶/二羟根瘤毒素合酶(SEQ ID NO:1)的N端氨基酸序列的第1-250位到1-801位,较佳地为1-250位至1-500位,更佳地为第1-320位至1-380位,最佳地为1-345位。
在另一优选例中,所述融合蛋白的氨基酸序列如SEQ ID NO:3所示。
在另一优选例中,所述谷氨酸脱氢酶是内源的或外源的。
在另一优选例中,所述是具有催化α-酮戊二酸在NADPH或NADH和铵根离子存在条件下生成L-谷氨酸的酶。
在另一优选例中,所述谷氨酸脱氢酶的来源选自下组:原核生物、真核生物、动物,或其组合。
在另一优选例中,所述原核生物选自下组:大肠杆菌、枯草芽孢杆菌、链霉菌、假单胞菌等,或其组合。
在另一优选例中,所述真核生物选自下组:酵母菌、拟南芥等。
在另一优选例中,所述谷氨酸脱氢酶的氨基酸序列如SEQ ID NO:4所示。
在另一优选例中,所述磷酸丝氨酸磷酸酶是内源的或外源的。
在另一优选例中,所述磷酸丝氨酸磷酸酶是具有催化2-氨基-1,3-丙二醇磷酸进行去磷酸反应生成2-氨基-1,3-丙二醇的酶。
在另一优选例中,所述磷酸丝氨酸磷酸酶的来源选自下组:原核生物、真核生物、动物,或其组合。
在另一优选例中,所述原核生物选自下组:大肠杆菌、枯草芽孢杆菌、链霉菌、假单胞菌等,或其组合。
在另一优选例中,所述真核生物选自下组:酵母菌、拟南芥等。
在另一优选例中,所述磷酸丝氨酸磷酸酶的氨基酸序列如SEQ ID NO:5所示。
在另一优选例中,所述增强活性可通过以下方法之一或组合来实现:表达该酶的同源或异源的编码基因,和/或增加所述编码基因的拷贝数,和/或改造所述编码基因的启动子以增强转录启动速度,和/或修改携带有所述编码基因的信使RNA的翻译调控区以增强翻译强度。
在另一优选例中,所述增强活性可通过以下方法实现:构建编码有对应融合蛋白或酶的序列的重组质粒,将所述重组质粒转化至受体菌株,得到工程菌株。
在另一优选例中,所述发酵条件中,氮源包括铵离子化合物,如(NH4)2SO4、(NH4)3PO4、NH4NO3等。
在本发明的第二方面,提供了一种融合蛋白,所述融合蛋白的氨基酸序列从N端到C端的构成如式I所示:
A-B 式I
其中,
组件A是一种蛋白功能增强分子部分的序列;
组件B是野生型磷酸二羟基丙酮氨基转移酶/二羟根瘤毒素合酶及其N端的片段序列。
在另一优选例中,所述组件B为所述野生型磷酸二羟基丙酮氨基转移酶/二羟根瘤毒素合酶(SEQ ID NO:1)的N端氨基酸序列的第1-250位到1-801位,较佳地为1-250位至1-500位,更佳地为第1-320位至1-380位,最佳地为1-345位。
在另一优选例中,所述融合蛋白的氨基酸序列如SEQ ID NO:3所示。
在本发明的第三方面,提供了一种稳定高产2-氨基-1,3-丙二醇的工程菌株的构建方法,所述方法包括:
(a)增强如本发明第二方面所述的融合蛋白的活性;
(b)任选地,增强谷氨酸脱氢酶的活性;和/或
(c)增强磷酸丝氨酸磷酸酶的活性。
在另一优选例中,所述菌株包括:大肠杆菌属(Escherichia coli)、蓝细菌、酵母菌等,或其组合。
在另一优选例中,所述菌株为大肠杆菌HMS174(DE3)。
在另一优选例中,所述载体质粒中包括抗性基因元件。
在另一优选例中,所述抗性包括:抗氨苄青霉素、抗卡那霉素、抗氯霉素,抗链霉素,或其组合。
在另一优选例中,所述构建方法包括步骤:
(i)构建编码有如本发明第二方面所述的融合蛋白序列的重组质粒I;和
(ii)将所述重组质粒I转化至受体菌株,得到第一工程菌株。
在另一优选例中,所述构建方法还包括步骤:
(iii)构建编码有谷氨酸脱氢酶序列的重组质粒II;和
(iv)将重组质粒II转化至第一工程菌株,得到第二工程菌株;
在另一优选例中,所述构建方法还包括步骤:
(v)将编码磷酸丝氨酸磷酸酶序列的核苷酸序列整合到重组质粒II中,得到重组质粒III;和
(vi)将重组质粒III转化至第一工程菌株,得到第三工程菌株。
在另一优选例中,所述构建方法还包括步骤:
(vii)筛选出能够稳定地使所整合的目的酶表达量较高的载体质粒;和/或
(viii)筛选出能够稳定高产2-氨基-1,3-丙二醇的受体菌株。
在另一优选例中,所述方法还包括步骤:
(ix)检测得到的第一工程菌株、第二工程菌株和/或第三工程菌株的2-氨基-1,3-丙二醇的发酵产量。
在另一优选例中,所述重组质粒I、II或III所用的载体质粒选自下组:pACYCDuet-1、pCDFDuet-1、pETDuet-1、pRSFDuet-1,或其组合。
在本发明的第四方面,提供了一种稳定高产2-氨基-1,3-丙二醇的工程菌株,所述菌株表达如本发明第二方面所述的融合蛋白。
在另一优选例中,所述菌株中谷氨酸脱氢酶的活性增强;和/或磷酸丝氨酸磷酸酶的活性增强。
在另一优选例中,所述工程菌株包括:大肠杆菌属(Escherichia coli)、蓝细菌、酵母菌等,或其组合。
在本发明的第五方面,提供了一种本发明第四方面所述的工程菌株的用途,所述工程菌株被用作发酵生产2-氨基-1,3-丙二醇及其衍生物的工程菌。
在另一优选例中,所述发酵生产过程中,所述工程菌株所利用的碳源包括:葡萄糖、甘油等简单碳源,或其组合。
在另一优选例中,以葡萄糖为作为原料直接发酵生产2-氨基-1,3-丙二醇。
应理解,在本发明范围内中,本发明的上述各技术特征和在下文(如实施例)中具体描述的各技术特征之间都可以互相组合,从而构成新的或优选的技术方案。限于篇幅,在此不再一一累述。
附图说明
图1显示了2-氨基-1,3-丙二醇的人工生物合成途径。
图2显示了不同磷酸二羟基丙酮氨基转移酶突变体融合蛋白对产物2-氨基-1,3-丙二醇合成的影响。
具体实施方式
本发明人经过广泛而深入地研究,进行大量的设计、筛选和分析,首次实现,在受体菌株中整合表达磷酸二羟基丙酮氨基转移酶或其突变体、高效表达谷氨酸脱氢酶和磷酸丝氨酸磷酸酶获得重组基因工程菌株,该菌株具有高效合成2-氨基-1,3-丙二醇的能力。在无甘油的发酵条件下,利用本发明构建的重组大肠杆菌系统在6L发酵罐水平,通过补料发酵工艺2-氨基-1,3-丙二醇产量达到15-20g/L。在此基础上完成了本发明。
术语
受体菌株
如本文所用,术语“受体菌株”、“本发明受体菌株”或“本发明出发菌株”可互换使用,都是指大肠杆菌Escherichia coli(较佳地,大肠杆菌HMS174(DE3))。
应理解,受体菌株不仅包括本发明实施例1中所用的大肠杆菌HMS174(DE3),还包括其衍生菌株以及其他类型的大肠杆菌菌株。
本发明生产方法
在本发明中,所述2-氨基-1,3-丙二醇的生物合成途径如图1所示。
本发明中的生物合成途径以糖酵解中间代谢产物磷酸二羟基丙酮为底物通过转氨生成2-氨基-1,3-丙二醇磷酸,再将中间代谢产物2-氨基-1,3-丙二醇磷酸的磷酸基团去除最终合成产物2-氨基-1,3-丙二醇。
所述的第一步转氨反应是2-氨基-1,3-丙二醇的人工生物合成途径的关键步骤,为了实现该人工设计的转氨反应和提高该反应的效率,本发明利用蛋白质工程手段获得了一个优化的转氨反应催化元件并对细胞的氨基供体内源供应能力进行了提升:
1)在目的菌株中表达能够特异性催化磷酸二羟基丙酮进行转氨反应的转氨酶基因。
2)在目的菌株中过表达来自大肠杆菌的谷氨酸脱氢酶,以优化工程菌株细胞内氨基供体L-谷氨酸的内源供应。
所述磷酸二羟基丙酮氨基转移酶和谷氨酸脱氢酶基因的引入,能够使得重组大肠杆菌过表达经蛋白质工程改性的异源磷酸二羟基丙酮氨基转移酶和内源的谷氨酸脱氢酶,从而独立并且高效地完成以L-谷氨酸作为氨基供体的磷酸二羟基丙酮的转氨反应,重组菌株能够高效地合成2-氨基-1,3-丙二醇。
在本发明中,所述磷酸二羟基丙酮氨基转移酶的氨基酸序列为SEQ ID No:1和包括由SEQ ID No:1序列N端不同长度的突变体,以及在上述磷酸二羟基丙酮氨基转移酶的突变体的N端上游融合蛋白功能增强分子部分(氨基酸序列见SEQ ID No:2)形成的融合突变体;所述谷氨酸脱氢酶的氨基酸序列为SEQ ID No:4。本发明仅以上述埃氏慢生根瘤菌来源的磷酸二羟基丙酮氨基转移酶及突变体和大肠杆菌来源的谷氨酸脱氢酶为例说明本发明的技术方案。
进一步优选,在上述重组大肠杆菌中过表达磷酸丝氨酸磷酸酶基因。使得重组大肠杆菌通过过表达上述基因,目的在于构建2-氨基-1,3-丙二醇的完整人工生物合成途径,提高将中间代谢产物2-氨基-1,3-丙二醇磷酸脱去磷酸基团的效率,进一步提高重组菌株合成2-氨基-1,3-丙二醇的效率。
在本发明中,所述磷酸丝氨酸磷酸酶可以来源于不用物种,本处仅以大肠杆菌内源的丝氨酸磷酸酶进行说明,其氨基酸序列见SEQ ID No:5。
本发明还进一步提供了前述任意一项所述的重组大肠杆菌在发酵法生产2-氨基-1,3-丙二醇方面的应用。
具体地说,所述应用为上述任意一项所述的重组大肠杆菌利用简单碳源直接发酵生产2-氨基-1,3-丙二醇。下面仅以葡萄糖进行说明。
作为优选,通过优化培养基及发酵条件可以进一步提高2-氨基-1,3-丙二醇的产量。
发酵培养基(g/L):葡萄糖10-100,KH2PO4 5-20,(NH4)2PO4 2-10,(NH4)2SO40-20,Citrate·2H2O 1-5,MgSO4·7H2O 0.5-5,yeast extract 0-10,适量的微量元素。培养基如果没有特别说明均以去离子水配置。
作为优选,发酵罐培养温度为30℃-37℃,通气量为1-3vvm,通过调整转速使得发酵罐内溶氧控制在10%及以上。
工程菌株构建
本发明提供了一种稳定高产2-氨基-1,3-丙二醇的基因工程菌株的构建方法,包括(但不限于)以下步骤:
(a)增强如本发明第二方面所述序列特征和活性特征的融合蛋白的活性;
(b)任选地,增强谷氨酸脱氢酶的活性;和/或
(c)增强磷酸丝氨酸磷酸酶的活性。
在另一优选例中,所述增强活性可通过以下方法之一或组合来实现:表达该酶的同源或异源的编码基因,和/或增加所述编码基因的拷贝数,和/或改造所述编码基因的启动子以增强转录启动速度,和/或修改携带有所述编码基因的信使RNA的翻译调控区以增强翻译强度。
在另一优选例中,所述增强活性可通过以下方法实现:构建编码有对应融合蛋白或酶的序列的重组质粒,将所述重组质粒转化至受体菌株,得到工程菌株。
在一优选实施方式中,所述构建方法包括步骤:
(i)构建编码有如本发明第二方面所述的融合蛋白序列的重组质粒I;和
(ii)将所述重组质粒I转化至受体菌株,得到第一工程菌株。
在另一优选例中,所述构建方法还包括步骤:
(iii)构建插入能编码有谷氨酸脱氢酶序列的重组质粒II;和
(iv)将重组质粒II转化至第一工程菌株,得到第二工程菌株;
在另一优选例中,所述构建方法还包括步骤:
(v)将编码磷酸丝氨酸磷酸酶序列的核苷酸序列整合到重组质粒II中,得到重组质粒III;和
(vi)将重组质粒III转化至第一工程菌株,得到第三工程菌株。
在另一优选例中,所述构建方法还包括步骤:
(vii)筛选出能够稳定地表达所选目的酶催化元件并能够促进较高水平合成产物2-氨基-1,3-丙二醇的质粒组合方式;和/或
(viii)筛选出能够稳定高产2-氨基-1,3-丙二醇的基因工程菌株。
在另一优选例中,所述方法还包括步骤:
(ix)检测得到的第一工程菌株、第二工程菌株和/或第三工程菌株的2-氨基-1,3-丙二醇的发酵产量。
因此,在本发明中,有第一、第二和第三共三种工程菌株,通过测试三种工程菌株的2-氨基-1,3-丙二醇的产量可知,此三种工程菌株相对于未经改造的受体菌株,均可显著提高2-氨基-1,3-丙二醇的产量。其中,同时过表达磷酸二羟基丙酮氨基转移酶突变体、谷氨酸脱氢酶和磷酸丝氨酸磷酸酶的工程菌株的产量的提高尤为显著。
本发明的主要优点包括:
1)本发明通过在野生大肠杆菌的基础上引入外源基因和代谢途径,成功拓展了糖酵解途径,实现了将糖酵解途径中间代谢产物磷酸二羟基丙酮转化为异源非天然代谢产物2-氨基-1,3-丙二醇,此外通过提高细胞内L-谷氨酸的自我循环供应和磷酸丝氨酸磷酸酶的过表达,提升了人工生物合成途径的效率,成功构建了2-氨基-1,3-丙二醇高效合成的重组大肠杆菌。上述重组大肠杆菌能够利用简单碳源直接发酵生成2-氨基-1,3-丙二醇,而且不需要借助其他任何外源酶,合成反应不需要涉及任何有毒化学试剂和化学催化剂,生产过程不需要高温高压和使用压力反应容器。
2)本发明弥补了现有2-氨基-1,3-丙二醇化学合成路线的诸多缺陷,首次获得了生物合成途径明确且运行高效稳定的人工生物合成途径,为建立大规模生物发酵法高效制备2-氨基-1,3-丙二醇奠定了催化元件、合成途径和菌株系统等的基础。利用本发明构建的重组大肠杆菌系统在6L发酵罐水平,通过补料发酵工艺2-氨基-1,3-丙二醇产量达到15-20g/L,填补了目前该领域的空白,具有重要的工业应用价值和前景。
下面结合具体实施例,进一步阐述本发明。应理解,这些实施例仅用于说明本发明而不用于限制本发明的范围。下列实施例中未注明具体条件的实验方法,通常按照常规条件如Sambrook等人,分子克隆:实验室手册(New York:Cold Spring Harbor LaboratoryPress,1989)中所述的条件,或按照《微生物:实验手册》(James Cappuccino和NatalieSherman编,Pearson Education出版社)中所述的条件,或按照制造厂商所建议的条件。
如无特别说明,实施例所用的材料和试剂均为市售产品。
材料
1.所用分子生物学酶试剂购自Thermo Fisher SCIENTIFIC公司,细菌基因组提取试剂盒和质粒提取试剂盒购自上海捷瑞生物工程,实验操作步骤参照相应说明书。
2.培养基:
摇瓶种子培养基(g/L):蛋白胨10,酵母粉5,NaCl 10,121℃,灭菌20min。
摇瓶发酵培养基(g/L):葡萄糖10-100,KH2PO4 5-20,(NH4)2PO4 2-10,(NH4)2SO4 0-20,Citrate·2H2O 1-5,MgSO4·7H2O 0.5-5,yeast extract 0-10,适量的微量元素。培养基如果没有特别说明均以去离子水配置。
在培养过程中,根据实际情况向培养基中加入适量的抗生素,例如,卡那霉素50mg/L和氯霉素35mg/L。
实施例1:磷酸二羟基丙酮氨基转移酶突变体的筛选
选择E.coli HMS174(DE3)作为验证所需的底盘细胞,考察不同突变体功能在体内的功能。
分别构建不同突变体重组表达质粒pET-30a-rtxA-D6,pET-30a-rtxA-D7,pET-30a-rtxA-D8,pET-30a-rtxA-D9和pET-30a-rtxA-D10分别转化至底盘细胞E.coli HMS174(DE3)获得重组菌株。
其中,融合突变体RtxA-D6为组件A蛋白功能增强分子部分融合组件B的N端801个残基,RtxA-D7为组件A蛋白功能增强分子部分融合组件B的N端499个残基,RtxA-D8为组件A蛋白功能增强分子部分融合组件B的N端383个残基,RtxA-D9为组件A蛋白功能增强分子部分融合组件B的N端345个残基,和RtxA-D10为组件A蛋白功能增强分子部分融合组件B的N端323个残基。
重组工程菌株发酵48h,测定细胞生物量和发酵液中产物2-氨基-1,3-丙二醇的含量。
测定结果如图2所示,其中,融合突变体RtxA-D9的细胞数及2-氨基-1,3-丙二醇产量均为最高。
实施例2:在大肠杆菌中过表达磷酸二羟基丙酮氨基转移酶及其突变体
该实施实例仅以磷酸二羟基丙酮氨基转移酶/二羟根瘤毒素合酶(氨基酸序列为SEQ ID No.1)的突变体之一进行阐明,即是由该序列N端345个氨基酸残基组成的序列,并将蛋白功能增强分子标签(SEQ ID No.2)融合在上述磷酸二羟基丙酮氨基转移酶核心序列的N端上游,该突变体命名为磷酸二羟基丙酮氨基转移酶(Dihydroxyacetone phosphateaminotransferase,DHAP-AT)DHAP-AT-D9,即为实施例1中的融合突变体RtxA-D9,其氨基酸序列见SEQ ID No.3。
经密码子优化的DHAP-AT-D9核苷酸序列由上海捷瑞生物工程公司进行人工合成,酶切位点为NdeⅠ和XhoⅠ。但是本发明不只是仅限于该突变体。将人工合成的DHAP-AT345序列利用NdeⅠ和XhoⅠ进行双酶切,将酶切片段回收后插入至用NdeⅠ和XhoⅠ双酶切处理的质粒pACYCDuet-1、pCDFDuet-1、pETDuet-1和pRSFDuet-1中,成功构建了重组质粒,pACYCDuet-dhap-AT-D9、pCDFDuet-dhap-AT-D9、pETDuet-dhap-AT-D9和pRSFDuet-dhap-AT-D9,并将上述4个质粒分别转化至大肠杆菌HMS174(DE3),成功构建了如下命名的重组大肠杆菌,E.coli pACYCDuet-dhap-AT-D95、E.coli pCDFDuet-dhap-AT-D9、E.coli pETDuet-dhap-AT-D9和E.coli pRSFDuet-dhap-AT-D9。
将上述五株重组大肠杆菌在250mL摇瓶中进行发酵,培养基为前述摇瓶发酵培养基其总体积为50mL,转速为220rpm,以0.1mM IPTG进行诱导异源蛋白的表达,发酵温度为30℃,发酵48h。
发酵48h后,利用高效液相色谱检测产物2-氨基-1,3-丙二醇的合成和计算其含量,重组菌株E.coli pACYCDuet-dhap-AT-D9、E.coli pCDFDuet-dhap-AT-D9、E.colipETDuet-dhap-AT-D9和E.coli pRSFDuet-dhap-AT-D9的产量分别为:0.18g/L,0.24g/L,0.27g/L和0.28g/L,野生型大肠杆菌没有合成2-氨基-1,3-丙二醇的能力。结果表明所选择的磷酸二羟基丙酮氨基转移酶突变体DHAP-AT-D9能够有效催化目标转氨反应,进而转化为目的产物2-氨基-1,3-丙二醇。作为优选将重组大肠杆菌E.coli pRSFDuet-dhap-AT-D9(LYC-1)作为后续研究的菌株。
实施例3:在重组大肠杆菌E.coli pRSFDuet-dhap-AT-D9(LYC-1)过表达谷氨酸脱氢酶。
所述谷氨酸脱氢酶是指不同来源的谷氨酸脱氢酶,本发明仅以来自大肠杆菌的谷氨酸脱氢(氨基酸序列为SEQ ID No.4)进行说明。以大肠杆菌HMS174(DE3)的基因组为模板,利用正向引物gdhAeco-F:5’-GAACATATGGATCAGACATATTCTCTGGAGTC-3’(酶切位点为NdeⅠ,SEQ ID NO.:6)和反向引物gdhAeco-B:5’-TTTAGATCTTAAATCACACCCTGCGCCAG-3’(酶切位点为BglⅡ,SEQ ID NO:7)扩增谷氨酸脱氢酶编码基因gdhA的核苷酸序列,并将该核苷酸序列用NdeⅠ和BglⅡ进行双酶切,酶切产物插入至用NdeⅠ和BglⅡ处理过的质粒pACYCDuet-1中,成功构建了重组质粒pACYCDuet-gdhAeco,将该重组质粒转化至前述构建的合成2-氨基-1,3-丙二醇的重组大肠杆菌E.coli pRSFDuet-dhap-AT-D9(LYC-1)中,成功构建了重组工程菌株LYC-4(E.coli pRSFDuet-dhap-AT-D9:pACYCDuet-gdhAeco)。
将上述构建的重组大肠杆菌LYC-4在250mL摇瓶中进行发酵,培养基为前述摇瓶发酵培养基其总体积为50mL,转速为220rpm,以0.1mM IPTG进行诱导异源蛋白的表达,发酵温度为30℃,发酵48h。发酵48h后,利用高效液相色谱检测产物2-氨基-1,3-丙二醇的合成和计算其含量,重组菌株LYC-4的2-氨基-1,3-丙二醇的产量为2.0g/L。结果表明过表达所述谷氨酸脱氢酶促进了产物2-氨基-1,3-丙二醇的生物合成效率。作为优选将重组大肠杆菌LYC-4作为2-氨基-1,3-丙二醇生物合成的菌株之一,并作为后续进一步研究的菌株。
实施例4:在重组大肠杆菌LYC-4中过表达磷酸丝氨酸磷酸酶。
所述磷酸丝氨酸磷酸酶是指不同来源的磷酸丝氨酸磷酸酶,本发明仅以来自大肠杆菌的磷酸丝氨酸磷酸酶(氨基酸序列为SEQ ID No.5)进行说明。以大肠杆菌HMS174(DE3)的基因组为模板,利用正向引物serBeco-F:5’-AATCCATGGGTCCTAACATTACCTGGTGC-3’(酶切位点为NcoⅠ,SEQ ID NO:8)和反向引物serBeco-B:5’-GAGAGGATCCTTACTTCTGATTCAGGCTG-3’(酶切位点为BamHⅠ,SEQ ID NO:9)扩增磷酸丝氨酸磷酸酶编码基因serB的核苷酸序列,并将该核苷酸序列用NcoⅠ和BamHⅠ进行双酶切,酶切产物插入至用NcoⅠ和BamHⅠ处理过的前述重组质粒pACYCDuet-gdhAeco中,成功构建了重组质粒pACYCDuet-serBeco-gdhAeco,将该重组质粒转化中前述构建的2-氨基-1,3-丙二醇合成重组大肠杆菌E.coli pRSFDuet-dhap-AT-D9(LYC-1)中,成功构建了重组工程菌株LYC-5(E.coli pRSFDuet-dhap-AT-D9:pACYCDuet-serBeco::gdhAeco)。
将上述构建的重组大肠杆菌LYC-5在250mL摇瓶中进行发酵,培养基为前述摇瓶发酵培养基其总体积为50mL,转速为220rpm,以0.1mM IPTG进行诱导异源蛋白的表达,发酵温度为30℃,发酵48h。发酵48h后,利用高效液相色谱检测产物2-氨基-1,3-丙二醇的合成和计算其含量,重组菌株LYC-5的2-氨基-1,3-丙二醇的产量为3.0g/L~5.0g/L。结果表明过表达所述磷酸丝氨酸磷酸酶能够显著促进产物2-氨基-1,3-丙二醇的生物合成效率。作为优选将重组大肠杆菌LYC-5作为2-氨基-1,3-丙二醇生物合成的菌株之一,并作为后续进一步研究的菌株。
实施例5:重组大肠杆菌LYC-5在6L发酵罐水平合成2-氨基-1,3-丙二醇的发酵工艺优化和应用
将上述构建的重组大肠杆菌LYC-5在6L发酵罐中进行工艺放大,并对发酵工艺参数进行优化。利用发酵培养基(g/L):葡萄糖10-100,KH2PO4 5-20,(NH4)2PO4 2-10,(NH4)2SO40-20,Citrate·2H2O 1-5,MgSO4·7H2O 0.5-5,yeast extract 0-10,适量的微量元素。培养基如果没有特别说明均以去离子水配置。在6L发酵罐中的发酵液初始体积为3L,转速为250rpm~1 200rpm之间,通气量为1~3vvm,溶氧控制10%以上,通过补料发酵工艺,重组大肠杆菌LYC-5发酵120h,产物2-氨基-1,3-丙二醇的产量达到15~20g/L,具有较高的2-氨基-1,3-丙二醇合成效率和重要的工业应用价值。
在本发明提及的所有文献都在本申请中引用作为参考,就如同每一篇文献被单独引用作为参考那样。此外应理解,在阅读了本发明的上述讲授内容之后,本领域技术人员可以对本发明作各种改动或修改,这些等价形式同样落于本申请所附权利要求书所限定的范围。
序列表
<110> 上海交通大学
<120> 微生物发酵法高效制备2-氨基-1,3-丙二醇
<130> P2018-0791
<160> 9
<170> PatentIn version 3.5
<210> 1
<211> 803
<212> PRT
<213> 埃氏慢生根瘤菌(Bradyrhizobium elkanii)
<400> 1
Met Leu Leu Asp Leu Ala Ser Arg Asp Gly Glu Phe Lys Glu Val Thr
1 5 10 15
Ala Arg Met Arg Arg Leu Met Leu Asn Leu Leu Gly Gly Ala Lys Asp
20 25 30
Tyr Ser Val Val Pro Ile Gln Gly Gly Gly Ser Phe Ala Met Glu Ala
35 40 45
Ala Leu Ser Ser Phe Val Ser Arg Asn Asp Lys Pro Leu Val Cys Ile
50 55 60
Asn Gly Ile Tyr Gly Glu Arg Ile Phe Lys Ile Leu Arg Leu Trp Gly
65 70 75 80
Val Glu Ala Leu Lys Leu Val Lys Arg Ala Thr Glu Pro Leu Glu Pro
85 90 95
Gln Glu Val Ala Glu Gln Leu Ser Arg Asn Pro Gly Val Thr His Leu
100 105 110
Cys Leu Val His Cys Glu Thr Thr Thr Gly Ile Val Asn Pro Val Asp
115 120 125
Ala Ile Ile Glu Glu Ala Arg Arg Arg Gly Val Lys Thr Ile Val Asp
130 135 140
Gly Met Ser Ser Phe Gly Ala Ile Asp Ile Asp Leu Ser Arg Gly Gly
145 150 155 160
Pro Asp Val Leu Val Thr Ser Ser Asn Lys Cys Ile Glu Gly Pro Pro
165 170 175
Gly Val Ala Phe Val Ile Ala Ser Arg Glu Leu Leu Glu Lys Ala Val
180 185 190
Gln Glu Pro Arg Ser Phe Val Leu Asp Val Arg Asp Gln Trp Leu Ser
195 200 205
Leu Glu Arg Thr Gly Glu Trp Arg Ser Thr Pro Pro Thr His Ile Val
210 215 220
Gln Ala Thr Thr Lys Ala Leu Glu Ile Leu Glu Gly Glu Gly Ile Asp
225 230 235 240
Ala Arg Arg Arg Arg Tyr Glu Lys Val Arg Asp Asp Leu Val Gln Glu
245 250 255
Leu Glu Gly Val Val Ser Pro Leu Leu Ser Ala Glu Leu Gln Ser Pro
260 265 270
Val Cys Val Ala Phe Arg Ala Pro Ser Gly Ile Ala Asp Gln Ala Gly
275 280 285
Phe Asp Gly Leu Tyr Arg His Leu Ala Ala His Asn Leu Tyr Ile Tyr
290 295 300
Ser Lys Leu His Leu Ala Thr Arg Ser Phe Arg Val Gly Cys Ile Gly
305 310 315 320
Glu Ile Gln Pro Ser Trp Ile Glu Gln Leu Gly Cys Ala Phe Arg Thr
325 330 335
Tyr Phe Arg Ser Gly Pro Ala Ser Ser Met Gly Thr Pro Ser Thr Arg
340 345 350
Gln Ala Cys Glu Arg Gly Val Glu Met Ser Ser Ser Phe Ala Lys Asp
355 360 365
Ser Gln Leu Pro Phe Ser Ala Glu Thr Ala Val Leu His Ala Gly Tyr
370 375 380
Arg Arg Asp Pro Val Thr Lys Ala Val Ala Val Pro Ile Tyr Gln Asn
385 390 395 400
Thr Ala Tyr Glu Leu Asp Gly Asp Leu Asn His Ile Ala Asp Val Tyr
405 410 415
Asn Val Lys Ala Asp Gly Phe Thr Tyr Thr Arg Ile Ile Asn Pro Thr
420 425 430
Thr Arg Ala Leu Glu Lys Arg Tyr Ala Ala Val Asp Met Gly Ser Asp
435 440 445
Ser Leu Ala Val Ala Ser Gly Gln Ala Ala Thr Phe Leu Ala Ile Val
450 455 460
Asn Leu Ser Ser Gly Glu Val Gly Asp Asn Ile Val Ala Ser Pro Tyr
465 470 475 480
Leu Tyr Gly Asn Thr Trp Asn Leu Leu His Asn Thr Leu Lys Arg Leu
485 490 495
Gly Ile Ser Val Arg Thr Ala Asp Pro Arg Arg Pro Glu Thr Phe Glu
500 505 510
Arg Ala Ile Asp Asp Arg Thr Ile Cys Leu Phe Gly Glu Val Ile Ser
515 520 525
Asn Pro Cys Leu Ile Pro Leu Pro Val Lys Gln Leu Ala Glu Ile Gly
530 535 540
Arg Lys His Gly Val Pro Leu Val Val Asp Asn Thr Thr Thr Pro Leu
545 550 555 560
Val Cys Arg Pro Ser Asp Leu Gly Ala Ala Ile Thr Thr Tyr Ser Ala
565 570 575
Thr Lys Tyr Ile Cys Gly His Gly Thr Thr Leu Gly Gly Leu Ile Val
580 585 590
Asp Asn Gly Lys Phe Ser Tyr Arg Gly Ala Ser Arg Phe Pro Leu Phe
595 600 605
Asn Ser Pro Asp Glu Ala His Gly Gly Ile Ile Trp Arg Asn Ala Leu
610 615 620
Gln Asp Val Asp Asp Leu Gly Lys Ser Glu Val Leu Leu Lys Ala Arg
625 630 635 640
Met Thr Trp Leu Arg Asp Thr Gly Ala Ala Ile Ala Pro Phe Ala Ser
645 650 655
Phe Gln Leu Ile Gln Gly Leu Glu Thr Leu Pro Leu Arg Met Lys Gln
660 665 670
His Cys Ala Asn Ala Arg Ile Val Ala Asp Val Leu Lys Glu His Pro
675 680 685
Lys Val Arg Arg Val Phe Tyr Pro Gly Leu Phe Glu Gly Ala Asp Arg
690 695 700
Glu Thr Val Asp Gln Thr Leu Asn Pro Ala Tyr Gly His Gly Ala Met
705 710 715 720
Val Met Phe Glu Val Glu Asp Glu Gln Ala Gly Arg Lys Phe Ile Gln
725 730 735
Asn Val Asp Leu Met Tyr His Val Ser Asn Val Gly Asp Ala Arg Thr
740 745 750
Leu Val Thr His Pro Val Ser Thr Thr His Thr Thr Val Pro Arg Glu
755 760 765
Lys Arg Glu Ala Ala Gly Ile Phe Gly Gly Ser Ile Arg Leu Cys Val
770 775 780
Gly Ile Glu Asp Val Asp Asp Ile Val Arg Asp Leu Asp Arg Ala Leu
785 790 795 800
Ser Ala Ile
<210> 2
<211> 22
<212> PRT
<213> 人工序列(artificial sequence)
<400> 2
Met Thr Arg Gln Arg Ser Leu Leu Thr Pro Gly Pro Leu Ser Leu Ser
1 5 10 15
Leu Ala Val Arg Ser Gln
20
<210> 3
<211> 367
<212> PRT
<213> 人工序列(artificial sequence)
<400> 3
Met Thr Arg Gln Arg Ser Leu Leu Thr Pro Gly Pro Leu Ser Leu Ser
1 5 10 15
Leu Ala Val Arg Ser Gln Met Leu Leu Asp Leu Ala Ser Arg Asp Gly
20 25 30
Glu Phe Lys Glu Val Thr Ala Arg Met Arg Arg Leu Met Leu Asn Leu
35 40 45
Leu Gly Gly Ala Lys Asp Tyr Ser Val Val Pro Ile Gln Gly Gly Gly
50 55 60
Ser Phe Ala Met Glu Ala Ala Leu Ser Ser Phe Val Ser Arg Asn Asp
65 70 75 80
Lys Pro Leu Val Cys Ile Asn Gly Ile Tyr Gly Glu Arg Ile Phe Lys
85 90 95
Ile Leu Arg Leu Trp Gly Val Glu Ala Leu Lys Leu Val Lys Arg Ala
100 105 110
Thr Glu Pro Leu Glu Pro Gln Glu Val Ala Glu Gln Leu Ser Arg Asn
115 120 125
Pro Gly Val Thr His Leu Cys Leu Val His Cys Glu Thr Thr Thr Gly
130 135 140
Ile Val Asn Pro Val Asp Ala Ile Ile Glu Glu Ala Arg Arg Arg Gly
145 150 155 160
Val Lys Thr Ile Val Asp Gly Met Ser Ser Phe Gly Ala Ile Asp Ile
165 170 175
Asp Leu Ser Arg Gly Gly Pro Asp Val Leu Val Thr Ser Ser Asn Lys
180 185 190
Cys Ile Glu Gly Pro Pro Gly Val Ala Phe Val Ile Ala Ser Arg Glu
195 200 205
Leu Leu Glu Lys Ala Val Gln Glu Pro Arg Ser Phe Val Leu Asp Val
210 215 220
Arg Asp Gln Trp Leu Ser Leu Glu Arg Thr Gly Glu Trp Arg Ser Thr
225 230 235 240
Pro Pro Thr His Ile Val Gln Ala Thr Thr Lys Ala Leu Glu Ile Leu
245 250 255
Glu Gly Glu Gly Ile Asp Ala Arg Arg Arg Arg Tyr Glu Lys Val Arg
260 265 270
Asp Asp Leu Val Gln Glu Leu Glu Gly Val Val Ser Pro Leu Leu Ser
275 280 285
Ala Glu Leu Gln Ser Pro Val Cys Val Ala Phe Arg Ala Pro Ser Gly
290 295 300
Ile Ala Asp Gln Ala Gly Phe Asp Gly Leu Tyr Arg His Leu Ala Ala
305 310 315 320
His Asn Leu Tyr Ile Tyr Ser Lys Leu His Leu Ala Thr Arg Ser Phe
325 330 335
Arg Val Gly Cys Ile Gly Glu Ile Gln Pro Ser Trp Ile Glu Gln Leu
340 345 350
Gly Cys Ala Phe Arg Thr Tyr Phe Arg Ser Gly Pro Ala Ser Ser
355 360 365
<210> 4
<211> 447
<212> PRT
<213> 大肠杆菌(Escherichia coli)
<400> 4
Met Asp Gln Thr Tyr Ser Leu Glu Ser Phe Leu Asn His Val Gln Lys
1 5 10 15
Arg Asp Pro Asn Gln Thr Glu Phe Ala Gln Ala Val Arg Glu Val Met
20 25 30
Thr Thr Leu Trp Pro Phe Leu Glu Gln Asn Pro Lys Tyr Arg Gln Met
35 40 45
Ser Leu Leu Glu Arg Leu Val Glu Pro Glu Arg Val Ile Gln Phe Arg
50 55 60
Val Val Trp Val Asp Asp Arg Asn Gln Ile Gln Val Asn Arg Ala Trp
65 70 75 80
Arg Val Gln Phe Ser Ser Ala Ile Gly Pro Tyr Lys Gly Gly Met Arg
85 90 95
Phe His Pro Ser Val Asn Leu Ser Ile Leu Lys Phe Leu Gly Phe Glu
100 105 110
Gln Thr Phe Lys Asn Ala Leu Thr Thr Leu Pro Met Gly Gly Gly Lys
115 120 125
Gly Gly Ser Asp Phe Asp Pro Lys Gly Lys Ser Glu Gly Glu Val Met
130 135 140
Arg Phe Cys Gln Ala Leu Met Thr Glu Leu Tyr Arg His Leu Gly Ala
145 150 155 160
Asp Thr Asp Val Pro Ala Gly Asp Ile Gly Val Gly Gly Arg Glu Val
165 170 175
Gly Phe Met Ala Gly Met Met Lys Lys Leu Ser Asn Asn Thr Ala Cys
180 185 190
Val Phe Thr Gly Lys Gly Leu Ser Phe Gly Gly Ser Leu Ile Arg Pro
195 200 205
Glu Ala Thr Gly Tyr Gly Leu Val Tyr Phe Thr Glu Ala Met Leu Lys
210 215 220
Arg His Gly Met Gly Phe Glu Gly Met Arg Val Ser Val Ser Gly Ser
225 230 235 240
Gly Asn Val Ala Gln Tyr Ala Ile Glu Lys Ala Met Glu Phe Gly Ala
245 250 255
Arg Val Ile Thr Ala Ser Asp Ser Ser Gly Thr Val Val Asp Glu Ser
260 265 270
Gly Phe Thr Lys Glu Lys Leu Ala Arg Leu Ile Glu Ile Lys Ala Ser
275 280 285
Arg Asp Gly Arg Val Ala Asp Tyr Ala Lys Glu Phe Gly Leu Val Tyr
290 295 300
Leu Glu Gly Gln Gln Pro Trp Ser Leu Pro Val Asp Ile Ala Leu Pro
305 310 315 320
Cys Ala Thr Gln Asn Glu Leu Asp Val Asp Ala Ala His Gln Leu Ile
325 330 335
Ala Asn Gly Val Lys Ala Val Ala Glu Gly Ala Asn Met Pro Thr Thr
340 345 350
Ile Glu Ala Thr Glu Leu Phe Gln Gln Ala Gly Val Leu Phe Ala Pro
355 360 365
Gly Lys Ala Ala Asn Ala Gly Gly Val Ala Thr Ser Gly Leu Glu Met
370 375 380
Ala Gln Asn Ala Ala Arg Leu Gly Trp Lys Ala Glu Lys Val Asp Ala
385 390 395 400
Arg Leu His His Ile Met Leu Asp Ile His His Ala Cys Val Glu His
405 410 415
Gly Gly Glu Gly Glu Gln Thr Asn Tyr Val Gln Gly Ala Asn Ile Ala
420 425 430
Gly Phe Val Lys Val Ala Asp Ala Met Leu Ala Gln Gly Val Ile
435 440 445
<210> 5
<211> 323
<212> PRT
<213> 大肠杆菌(Escherichia coli)
<400> 5
Met Gly Pro Asn Ile Thr Trp Cys Asp Leu Pro Glu Asp Val Ser Leu
1 5 10 15
Trp Pro Gly Leu Pro Leu Ser Leu Ser Gly Asp Glu Val Met Pro Leu
20 25 30
Asp Tyr His Ala Gly Arg Ser Gly Trp Leu Leu Tyr Gly Arg Gly Leu
35 40 45
Asp Lys Gln Arg Leu Thr Gln Tyr Gln Ser Lys Leu Gly Ala Ala Met
50 55 60
Val Ile Val Ala Ala Trp Cys Val Glu Asp Tyr Gln Val Ile Arg Leu
65 70 75 80
Ala Gly Ser Leu Thr Ala Arg Ala Thr Arg Leu Ala His Glu Ala Gln
85 90 95
Leu Asp Val Ala Pro Leu Gly Lys Ile Pro His Leu Arg Thr Pro Gly
100 105 110
Leu Leu Val Met Asp Met Asp Ser Thr Ala Ile Gln Ile Glu Cys Ile
115 120 125
Asp Glu Ile Ala Lys Leu Ala Gly Thr Gly Glu Met Val Ala Glu Val
130 135 140
Thr Glu Arg Ala Met Arg Gly Glu Leu Asp Phe Thr Ala Ser Leu Arg
145 150 155 160
Ser Arg Val Ala Thr Leu Lys Gly Ala Asp Ala Asn Ile Leu Gln Gln
165 170 175
Val Arg Glu Asn Leu Pro Leu Met Pro Gly Leu Thr Gln Leu Val Leu
180 185 190
Lys Leu Glu Thr Leu Gly Trp Lys Val Ala Ile Ala Ser Gly Gly Phe
195 200 205
Thr Phe Phe Ala Glu Tyr Leu Arg Asp Lys Leu Arg Leu Thr Ala Val
210 215 220
Val Ala Asn Glu Leu Glu Ile Met Asp Gly Lys Phe Thr Gly Asn Val
225 230 235 240
Ile Gly Asp Ile Val Asp Ala Gln Tyr Lys Ala Lys Thr Leu Thr Arg
245 250 255
Leu Ala Gln Glu Tyr Glu Ile Pro Leu Ala Gln Thr Val Ala Ile Gly
260 265 270
Asp Gly Ala Asn Asp Leu Pro Met Ile Lys Ala Ala Gly Leu Gly Ile
275 280 285
Ala Tyr His Ala Lys Pro Lys Val Asn Glu Lys Ala Glu Val Thr Ile
290 295 300
Arg His Ala Asp Leu Met Gly Val Phe Cys Ile Leu Ser Gly Ser Leu
305 310 315 320
Asn Gln Lys
<210> 6
<211> 32
<212> DNA
<213> 人工序列(artificial sequence)
<400> 6
gaacatatgg atcagacata ttctctggag tc 32
<210> 7
<211> 29
<212> DNA
<213> 人工序列(artificial sequence)
<400> 7
tttagatctt aaatcacacc ctgcgccag 29
<210> 8
<211> 29
<212> DNA
<213> 人工序列(artificial sequence)
<400> 8
aatccatggg tcctaacatt acctggtgc 29
<210> 9
<211> 29
<212> DNA
<213> 人工序列(artificial sequence)
<400> 9
gagaggatcc ttacttctga ttcaggctg 29
Claims (18)
1.一种生产2-氨基-1,3-丙二醇的方法,其特征在于,包括步骤:
(a)在适合发酵的条件下,培养工程菌,从而产生2-氨基-1,3-丙二醇;
(b)任选地从发酵产物中分离2-氨基-1,3-丙二醇;
所述工程菌具有以下特征:
(i)表达外源的磷酸二羟基丙酮氨基转移酶,并且所述磷酸二羟基丙酮氨基转移酶的氨基酸序列从N端到C端的构成如式I所示:
A-B 式I
其中,
组件A是一种蛋白功能增强分子,其氨基酸序列如SEQ ID NO: 2所示;
组件B是野生型磷酸二羟基丙酮氨基转移酶或其N端氨基酸序列的第1-345位、第1-383位、第1-499位或第1-801位,所述野生型磷酸二羟基丙酮氨基转移酶的序列如SEQ ID NO:1所示;和
(ii)任选地具有增强活性的谷氨酸脱氢酶;
(iii)具有增强活性的磷酸丝氨酸磷酸酶,所述磷酸丝氨酸磷酸酶是具有催化2-氨基-1,3-丙二醇磷酸进行去磷酸反应生成2-氨基-1,3-丙二醇的酶;
并且,所述发酵条件中,无甘油。
2.如权利要求1所述的方法,其特征在于,所述工程菌为经改造的受体菌株,所述受体菌株选自下组:原核生物或真核生物。
3.如权利要求2所述的方法,其特征在于,所述受体菌株为大肠杆菌HMS174(DE3)。
4.如权利要求1所述的方法,其特征在于,所述谷氨酸脱氢酶的氨基酸序列如SEQ IDNO: 4所示。
5.如权利要求1所述的方法,其特征在于,所述磷酸丝氨酸磷酸酶的氨基酸序列如SEQID NO: 5所示。
6.如权利要求1所述的方法,其特征在于,所述发酵条件中,氮源包括铵离子化合物。
7.如权利要求6所述的方法,其特征在于,所述铵离子化合物为(NH4)2SO4、(NH4)3PO4或NH4NO3。
8.一种融合蛋白,其特征在于,所述融合蛋白的氨基酸序列从N端到C端的构成如式I所示:
A-B 式I
其中,
组件A是一种蛋白功能增强分子,其氨基酸序列如SEQ ID NO: 2所示;
组件B是野生型磷酸二羟基丙酮氨基转移酶或其N端氨基酸序列的第1-345位、第1-383位、第1-499位或第1-801位,所述野生型磷酸二羟基丙酮氨基转移酶的序列如SEQ ID NO:1所示。
9.如权利要求8所述的融合蛋白,其特征在于,所述组件B为所述野生型磷酸二羟基丙酮氨基转移酶的N端氨基酸序列的第1-499位,所述野生型磷酸二羟基丙酮氨基转移酶的序列如SEQ ID NO: 1所示。
10.如权利要求8所述的融合蛋白,其特征在于,所述组件B为所述野生型磷酸二羟基丙酮氨基转移酶的N端氨基酸序列的第1-383位,所述野生型磷酸二羟基丙酮氨基转移酶的序列如SEQ ID NO: 1所示。
11.如权利要求8所述的融合蛋白,其特征在于,所述组件B为所述野生型磷酸二羟基丙酮氨基转移酶的N端氨基酸序列的第1-345位,所述野生型磷酸二羟基丙酮氨基转移酶的序列如SEQ ID NO: 1所示。
12.如权利要求8所述的融合蛋白,其特征在于,所述融合蛋白的氨基酸序列如SEQ IDNO: 3所示。
13.一种稳定高产2-氨基-1,3-丙二醇的工程菌株的构建方法,其特征在于,所述方法包括:使所述菌株表达如权利要求8至12中任一项所述的融合蛋白和磷酸丝氨酸磷酸酶,和任选地过表达谷氨酸脱氢酶,从而增强谷氨酸脱氢酶的活性;其中,所述磷酸丝氨酸磷酸酶是具有催化2-氨基-1,3-丙二醇磷酸进行去磷酸反应生成2-氨基-1,3-丙二醇的酶。
14.一种稳定高产2-氨基-1,3-丙二醇的工程菌株,其特征在于,所述菌株表达如权利要求8至12中任一项所述的融合蛋白和磷酸丝氨酸磷酸酶,和任选地过表达谷氨酸脱氢酶,从而增强谷氨酸脱氢酶的活性;
其中,所述磷酸丝氨酸磷酸酶是具有催化2-氨基-1,3-丙二醇磷酸进行去磷酸反应生成2-氨基-1,3-丙二醇的酶。
15.如权利要求14所述的工程菌株,其特征在于,所述菌株中谷氨酸脱氢酶的活性增强;和磷酸丝氨酸磷酸酶的活性增强。
16.一种权利要求14或15所述的工程菌株的用途,其特征在于,所述工程菌株被用作发酵生产2-氨基-1,3-丙二醇及其衍生物的工程菌。
17.如权利要求16所述的用途,其特征在于,所述发酵生产过程中,所述工程菌株所利用的碳源包括简单碳源,其中所述简单碳源选自:葡萄糖、甘油,或其组合。
18.如权利要求16所述的用途,其特征在于,所述工程菌株以葡萄糖为作为原料直接发酵生产2-氨基-1,3-丙二醇。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201811296012.8A CN109321610B (zh) | 2018-11-01 | 2018-11-01 | 微生物发酵法高效制备2-氨基-1,3-丙二醇 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201811296012.8A CN109321610B (zh) | 2018-11-01 | 2018-11-01 | 微生物发酵法高效制备2-氨基-1,3-丙二醇 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN109321610A CN109321610A (zh) | 2019-02-12 |
CN109321610B true CN109321610B (zh) | 2022-11-04 |
Family
ID=65260246
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201811296012.8A Active CN109321610B (zh) | 2018-11-01 | 2018-11-01 | 微生物发酵法高效制备2-氨基-1,3-丙二醇 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN109321610B (zh) |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998024755A1 (en) * | 1996-12-04 | 1998-06-11 | Dibra S.P.A. | Process for the purification of an aminoalcohol |
CN1379818A (zh) * | 1999-08-18 | 2002-11-13 | 纳幕尔杜邦公司 | 用于生产高效价1,3-丙二醇的生物学方法 |
CN1860221A (zh) * | 2002-10-04 | 2006-11-08 | 纳幕尔杜邦公司 | 高产量生物生产1,3-丙二醇的方法 |
CN106906248A (zh) * | 2017-03-28 | 2017-06-30 | 清华大学 | 一种利用重组微生物发酵生产1,3‑丙二醇的方法 |
-
2018
- 2018-11-01 CN CN201811296012.8A patent/CN109321610B/zh active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998024755A1 (en) * | 1996-12-04 | 1998-06-11 | Dibra S.P.A. | Process for the purification of an aminoalcohol |
CN1379818A (zh) * | 1999-08-18 | 2002-11-13 | 纳幕尔杜邦公司 | 用于生产高效价1,3-丙二醇的生物学方法 |
CN1860221A (zh) * | 2002-10-04 | 2006-11-08 | 纳幕尔杜邦公司 | 高产量生物生产1,3-丙二醇的方法 |
CN106906248A (zh) * | 2017-03-28 | 2017-06-30 | 清华大学 | 一种利用重组微生物发酵生产1,3‑丙二醇的方法 |
Non-Patent Citations (1)
Title |
---|
《RtxA [Bradyrhizobium elkanii]》;NCBI;《GenBank》;20180929;BAB55900.1 * |
Also Published As
Publication number | Publication date |
---|---|
CN109321610A (zh) | 2019-02-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP3564366B1 (en) | A novel isopropylmalate synthase variant and a method of producing l-leucine using the same | |
WO2018114762A1 (en) | Improved glycerol free ethanol production | |
KR20150045447A (ko) | 재조합 미생물 및 이에 대한 용도 | |
KR101359844B1 (ko) | 퀴놀린산을 생산하는 재조합 미생물 및 이를 이용한 퀴놀린산의 생산 방법 | |
JP2016524919A (ja) | 新規な変異オルニチンデカルボキシラーゼタンパク質及びその用途 | |
US20140134690A1 (en) | Microbes and methods for producing 1-propanol | |
CN109321610B (zh) | 微生物发酵法高效制备2-氨基-1,3-丙二醇 | |
CN109628476B (zh) | 一种利用全细胞转化生产4-羟基异亮氨酸的方法 | |
CN118339281A (zh) | 工程化酶及制备和使用方法 | |
CN112852774A (zh) | 磷酸果糖氨基转移酶编码基因及酶的制备与应用 | |
CN108410875B (zh) | 一种提高重组大肠杆菌中1,2,4-丁三醇产量的方法 | |
CN103589756A (zh) | 利用l-乳酸生物合成s-1,2-丙二醇的方法 | |
CN113913399A (zh) | 来源于Candida maltosa Xu316的酮基泛解酸内酯还原酶 | |
CN116096869A (zh) | 工程化酶及其制备和使用方法 | |
CN113122563A (zh) | 构建r-3-氨基丁酸生产菌的方法 | |
EP3489361B1 (en) | Microorganism having activity of acyltransferase and use thereof | |
CN114127102A (zh) | 工程化乙酸激酶变体酶 | |
CN111032874A (zh) | 表达活性d-脯氨酸还原酶的微生物以及生产活性d-脯氨酸还原酶的方法 | |
EP4389874A1 (en) | Genetically modified microorganisms for the manufacture of compounds derived from dihydroxyacetone phosphate | |
CN114276970B (zh) | 一种产1,3-丙二醇的基因工程菌 | |
KR101251620B1 (ko) | 아데노신 디아미네이즈의 효소 활성 증가 방법, 상기활성이 증가된 아데노신 디아미네이즈 변이체, 및 상기변이체를 이용한 디옥시구아노신의 생산방법 | |
EP4431609A1 (en) | Method for improving 2, 4 dihydroxybutyric acid production and yield | |
Guo et al. | Enhanced Biosynthesis of d-Allulose from a d-Xylose–Methanol Mixture and Its Self-Inductive Detoxification by Using Antisense RNAs in Escherichia coli | |
CN113528366A (zh) | 一种产beta-丙氨酸酵母菌及其构建方法 | |
CN118147245A (zh) | 水杨胺的生物合成方法及体系 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |