AU2005298341B2 - Methods for heterologous expression of secondary metabolites - Google Patents
Methods for heterologous expression of secondary metabolites Download PDFInfo
- Publication number
- AU2005298341B2 AU2005298341B2 AU2005298341A AU2005298341A AU2005298341B2 AU 2005298341 B2 AU2005298341 B2 AU 2005298341B2 AU 2005298341 A AU2005298341 A AU 2005298341A AU 2005298341 A AU2005298341 A AU 2005298341A AU 2005298341 B2 AU2005298341 B2 AU 2005298341B2
- Authority
- AU
- Australia
- Prior art keywords
- host cell
- gene
- biosynthetic pathway
- genes
- vector
- 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.)
- Ceased
Links
- 229930000044 secondary metabolite Natural products 0.000 title claims abstract description 77
- 238000000034 method Methods 0.000 title claims abstract description 72
- 230000014509 gene expression Effects 0.000 title claims abstract description 46
- 230000006696 biosynthetic metabolic pathway Effects 0.000 claims abstract description 55
- 210000004027 cell Anatomy 0.000 claims description 135
- 108090000623 proteins and genes Proteins 0.000 claims description 118
- 239000013598 vector Substances 0.000 claims description 61
- 241000589516 Pseudomonas Species 0.000 claims description 47
- 230000037361 pathway Effects 0.000 claims description 47
- 241000588724 Escherichia coli Species 0.000 claims description 35
- 229930001119 polyketide Natural products 0.000 claims description 24
- 102000004190 Enzymes Human genes 0.000 claims description 23
- 108090000790 Enzymes Proteins 0.000 claims description 23
- 230000001939 inductive effect Effects 0.000 claims description 22
- 108010020764 Transposases Proteins 0.000 claims description 21
- MZFOKIKEPGUZEN-FBMOWMAESA-N methylmalonyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C(C(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 MZFOKIKEPGUZEN-FBMOWMAESA-N 0.000 claims description 19
- 150000003881 polyketide derivatives Chemical class 0.000 claims description 18
- 230000015572 biosynthetic process Effects 0.000 claims description 17
- 102000008579 Transposases Human genes 0.000 claims description 13
- 229930001118 polyketide hybrid Natural products 0.000 claims description 10
- 125000003308 polyketide hybrid group Chemical group 0.000 claims description 10
- 239000000758 substrate Substances 0.000 claims description 10
- 238000003786 synthesis reaction Methods 0.000 claims description 10
- 238000012258 culturing Methods 0.000 claims description 9
- 238000012216 screening Methods 0.000 claims description 6
- 230000001131 transforming effect Effects 0.000 claims description 5
- 241000607142 Salmonella Species 0.000 claims description 4
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 2
- 229930195729 fatty acid Natural products 0.000 claims description 2
- 239000000194 fatty acid Substances 0.000 claims description 2
- 150000004665 fatty acids Chemical class 0.000 claims description 2
- 150000003384 small molecules Chemical class 0.000 claims description 2
- 108020004414 DNA Proteins 0.000 abstract description 53
- OPTHDMYHZAOJMC-NHVZZHALSA-N myxochromide s Chemical class C\C=C\C=C\C=C\C=C\C=C\C=C\C=C\C=C\C(=O)N(C)C1C(C)OC(=O)C(CCC(N)=O)NC(=O)C(C)NC(=O)C(C)NC(=O)C(CC(C)C)NC1=O OPTHDMYHZAOJMC-NHVZZHALSA-N 0.000 abstract description 27
- 210000000349 chromosome Anatomy 0.000 abstract description 19
- 102000053602 DNA Human genes 0.000 abstract description 9
- 241000589776 Pseudomonas putida Species 0.000 description 50
- 108091008053 gene clusters Proteins 0.000 description 46
- 238000004519 manufacturing process Methods 0.000 description 36
- 239000013612 plasmid Substances 0.000 description 28
- 229930184386 Myxochromide Natural products 0.000 description 26
- 230000010354 integration Effects 0.000 description 26
- XKTFQMCPGMTBMD-FYHMSGCOSA-N myxothiazol Chemical compound NC(=O)\C=C(\OC)[C@H](C)[C@@H](OC)\C=C\C1=CSC(C=2N=C(SC=2)[C@@H](C)\C=C\C=C\C(C)C)=N1 XKTFQMCPGMTBMD-FYHMSGCOSA-N 0.000 description 26
- XKTFQMCPGMTBMD-UHFFFAOYSA-N myxothiazol A Natural products NC(=O)C=C(OC)C(C)C(OC)C=CC1=CSC(C=2N=C(SC=2)C(C)C=CC=CC(C)C)=N1 XKTFQMCPGMTBMD-UHFFFAOYSA-N 0.000 description 26
- 229930187386 myxothiazol Natural products 0.000 description 24
- 150000001875 compounds Chemical class 0.000 description 21
- ZIYVHBGGAOATLY-UHFFFAOYSA-N methylmalonic acid Chemical compound OC(=O)C(C)C(O)=O ZIYVHBGGAOATLY-UHFFFAOYSA-N 0.000 description 20
- 239000000047 product Substances 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000012634 fragment Substances 0.000 description 18
- 238000010353 genetic engineering Methods 0.000 description 18
- 238000002703 mutagenesis Methods 0.000 description 16
- 231100000350 mutagenesis Toxicity 0.000 description 16
- 238000010367 cloning Methods 0.000 description 15
- 230000021615 conjugation Effects 0.000 description 15
- 239000000284 extract Substances 0.000 description 15
- RROPNRTUMVVUED-UHFFFAOYSA-N flaviolin Chemical compound C1=C(O)C=C2C(=O)C(O)=CC(=O)C2=C1O RROPNRTUMVVUED-UHFFFAOYSA-N 0.000 description 15
- 230000009466 transformation Effects 0.000 description 15
- 238000004458 analytical method Methods 0.000 description 13
- 238000004128 high performance liquid chromatography Methods 0.000 description 13
- 238000005215 recombination Methods 0.000 description 13
- 230000017105 transposition Effects 0.000 description 13
- 230000001851 biosynthetic effect Effects 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 102000004169 proteins and genes Human genes 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 11
- 238000001514 detection method Methods 0.000 description 11
- 238000002744 homologous recombination Methods 0.000 description 11
- 230000006801 homologous recombination Effects 0.000 description 11
- 230000006798 recombination Effects 0.000 description 11
- 238000012546 transfer Methods 0.000 description 11
- 238000003780 insertion Methods 0.000 description 10
- 230000037431 insertion Effects 0.000 description 10
- 108010078791 Carrier Proteins Proteins 0.000 description 9
- 241000863434 Myxococcales Species 0.000 description 9
- 102000004357 Transferases Human genes 0.000 description 9
- 108090000992 Transferases Proteins 0.000 description 9
- 230000008901 benefit Effects 0.000 description 9
- XMQFTWRPUQYINF-UHFFFAOYSA-N bensulfuron-methyl Chemical compound COC(=O)C1=CC=CC=C1CS(=O)(=O)NC(=O)NC1=NC(OC)=CC(OC)=N1 XMQFTWRPUQYINF-UHFFFAOYSA-N 0.000 description 9
- 229930027917 kanamycin Natural products 0.000 description 9
- 229960000318 kanamycin Drugs 0.000 description 9
- 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 9
- 229930182823 kanamycin A Natural products 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- 239000002207 metabolite Substances 0.000 description 9
- 231100000331 toxic Toxicity 0.000 description 9
- 230000002588 toxic effect Effects 0.000 description 9
- 241000894006 Bacteria Species 0.000 description 8
- 102000014914 Carrier Proteins Human genes 0.000 description 8
- 230000001580 bacterial effect Effects 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 238000004520 electroporation Methods 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 210000004436 artificial bacterial chromosome Anatomy 0.000 description 6
- 230000000975 bioactive effect Effects 0.000 description 6
- 125000000830 polyketide group Chemical group 0.000 description 6
- 241000186361 Actinobacteria <class> Species 0.000 description 5
- 102000019010 Methylmalonyl-CoA Mutase Human genes 0.000 description 5
- 108010051862 Methylmalonyl-CoA mutase Proteins 0.000 description 5
- 241000478624 Sorangium cellulosum So ce56 Species 0.000 description 5
- 241000863001 Stigmatella aurantiaca Species 0.000 description 5
- 239000004098 Tetracycline Substances 0.000 description 5
- 102000005488 Thioesterase Human genes 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 230000003115 biocidal effect Effects 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 239000013613 expression plasmid Substances 0.000 description 5
- 101150066555 lacZ gene Proteins 0.000 description 5
- 101150028473 mta gene Proteins 0.000 description 5
- 108020004707 nucleic acids Proteins 0.000 description 5
- 102000039446 nucleic acids Human genes 0.000 description 5
- 150000007523 nucleic acids Chemical class 0.000 description 5
- ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluic acid Chemical compound CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 0.000 description 5
- 230000010076 replication Effects 0.000 description 5
- 241000894007 species Species 0.000 description 5
- 229930101283 tetracycline Natural products 0.000 description 5
- 229960002180 tetracycline Drugs 0.000 description 5
- 235000019364 tetracycline Nutrition 0.000 description 5
- 150000003522 tetracyclines Chemical class 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- 108020002982 thioesterase Proteins 0.000 description 5
- 101150044170 trpE gene Proteins 0.000 description 5
- ZIYVHBGGAOATLY-FIBGUPNXSA-N 2-(trideuteriomethyl)propanedioic acid Chemical compound [2H]C([2H])([2H])C(C(O)=O)C(O)=O ZIYVHBGGAOATLY-FIBGUPNXSA-N 0.000 description 4
- HCJMNOSIAGSZBM-UHFFFAOYSA-N 6-methylsalicylic acid Chemical compound CC1=CC=CC(O)=C1C(O)=O HCJMNOSIAGSZBM-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
- 101710146995 Acyl carrier protein Proteins 0.000 description 4
- 108700010070 Codon Usage Proteins 0.000 description 4
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 4
- 102000030503 Methylmalonyl-CoA epimerase Human genes 0.000 description 4
- 108700026244 Open Reading Frames Proteins 0.000 description 4
- 108010030975 Polyketide Synthases Proteins 0.000 description 4
- 241000589615 Pseudomonas syringae Species 0.000 description 4
- 101001001483 Serratia sp. (strain ATCC 39006) Probable acyl carrier protein PigG Proteins 0.000 description 4
- 108010084455 Zeocin Proteins 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 108091000124 methylmalonyl-CoA epimerase Proteins 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- CWCMIVBLVUHDHK-ZSNHEYEWSA-N phleomycin D1 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC[C@@H](N=1)C=1SC=C(N=1)C(=O)NCCCCNC(N)=N)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C CWCMIVBLVUHDHK-ZSNHEYEWSA-N 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 101000979117 Curvularia clavata Nonribosomal peptide synthetase Proteins 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 241000238631 Hexapoda Species 0.000 description 3
- 241000863422 Myxococcus xanthus Species 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- 240000007019 Oxalis corniculata Species 0.000 description 3
- 241000589614 Pseudomonas stutzeri Species 0.000 description 3
- 101150010882 S gene Proteins 0.000 description 3
- 241000187747 Streptomyces Species 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 238000000855 fermentation Methods 0.000 description 3
- 230000004151 fermentation Effects 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 238000001415 gene therapy Methods 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 239000000401 methanolic extract Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000002741 site-directed mutagenesis Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 101150055869 25 gene Proteins 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000636159 Candidatus Solibacter usitatus Ellin6076 Species 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 229920002101 Chitin Polymers 0.000 description 2
- RGJOEKWQDUBAIZ-IBOSZNHHSA-N CoASH Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS)O[C@H]1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-IBOSZNHHSA-N 0.000 description 2
- 241000206602 Eukaryota Species 0.000 description 2
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 2
- 239000006142 Luria-Bertani Agar Substances 0.000 description 2
- 102000004317 Lyases Human genes 0.000 description 2
- 108090000856 Lyases Proteins 0.000 description 2
- LTYOQGRJFJAKNA-KKIMTKSISA-N Malonyl CoA Natural products S(C(=O)CC(=O)O)CCNC(=O)CCNC(=O)[C@@H](O)C(CO[P@](=O)(O[P@](=O)(OC[C@H]1[C@@H](OP(=O)(O)O)[C@@H](O)[C@@H](n2c3ncnc(N)c3nc2)O1)O)O)(C)C LTYOQGRJFJAKNA-KKIMTKSISA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 101100408135 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) phnA gene Proteins 0.000 description 2
- 241000320117 Pseudomonas putida KT2440 Species 0.000 description 2
- 241000259045 Pseudomonas syringae pv. tomato str. DC3000 Species 0.000 description 2
- 108090001066 Racemases and epimerases Proteins 0.000 description 2
- 241000862997 Sorangium cellulosum Species 0.000 description 2
- 241000197447 Stigmatella aurantiaca DW4/3-1 Species 0.000 description 2
- 241001655322 Streptomycetales Species 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- KNGQILZSJUUYIK-VIFPVBQESA-N [(2R)-4-hydroxy-3,3-dimethyl-1-oxo-1-[[3-oxo-3-(2-sulfanylethylamino)propyl]amino]butan-2-yl] dihydrogen phosphate Chemical group OCC(C)(C)[C@@H](OP(O)(O)=O)C(=O)NCCC(=O)NCCS KNGQILZSJUUYIK-VIFPVBQESA-N 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 230000004075 alteration Effects 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
- 230000003321 amplification Effects 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 238000011088 calibration curve Methods 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 2
- 239000005516 coenzyme A Substances 0.000 description 2
- 229940093530 coenzyme a Drugs 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 231100000599 cytotoxic agent Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 239000002619 cytotoxin Substances 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 2
- 229930013356 epothilone Natural products 0.000 description 2
- 150000003883 epothilone derivatives Chemical class 0.000 description 2
- 229960003276 erythromycin Drugs 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 2
- 210000000688 human artificial chromosome Anatomy 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 238000002743 insertional mutagenesis Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- LTYOQGRJFJAKNA-DVVLENMVSA-N malonyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CC(O)=O)O[C@H]1N1C2=NC=NC(N)=C2N=C1 LTYOQGRJFJAKNA-DVVLENMVSA-N 0.000 description 2
- 230000037353 metabolic pathway Effects 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 108010000785 non-ribosomal peptide synthase Proteins 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 231100000683 possible toxicity Toxicity 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 239000013558 reference substance Substances 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 210000003705 ribosome Anatomy 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 2
- 238000001877 single-ion monitoring Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000000844 transformation Methods 0.000 description 2
- 238000002211 ultraviolet spectrum Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- JLPUXFOGCDVKGO-TUAOUCFPSA-N (-)-geosmin Chemical compound C1CCC[C@]2(O)[C@@H](C)CCC[C@]21C JLPUXFOGCDVKGO-TUAOUCFPSA-N 0.000 description 1
- UQIHHGNTYLFRNX-ALKRTJFJSA-N (2s)-5-[[(2r)-1-(carboxymethylamino)-1-oxo-3-sulfanylpropan-2-yl]amino]-2-(2-hydroxypropanoylamino)-5-oxopentanoic acid Chemical compound CC(O)C(=O)N[C@H](C(O)=O)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O UQIHHGNTYLFRNX-ALKRTJFJSA-N 0.000 description 1
- DLKUYSQUHXBYPB-NSSHGSRYSA-N (2s,4r)-4-[[2-[(1r,3r)-1-acetyloxy-4-methyl-3-[3-methylbutanoyloxymethyl-[(2s,3s)-3-methyl-2-[[(2r)-1-methylpiperidine-2-carbonyl]amino]pentanoyl]amino]pentyl]-1,3-thiazole-4-carbonyl]amino]-2-methyl-5-(4-methylphenyl)pentanoic acid Chemical compound N([C@@H]([C@@H](C)CC)C(=O)N(COC(=O)CC(C)C)[C@H](C[C@@H](OC(C)=O)C=1SC=C(N=1)C(=O)N[C@H](C[C@H](C)C(O)=O)CC=1C=CC(C)=CC=1)C(C)C)C(=O)[C@H]1CCCCN1C DLKUYSQUHXBYPB-NSSHGSRYSA-N 0.000 description 1
- HQZOLNNEQAKEHT-UHFFFAOYSA-N (3R,4S,5R,6S,7S,9R,11R,12S,13R,14R)-14-ethyl-4,6,12-trihydroxy-3,5,7,9,11,13-hexamethyloxacyclotetradecane-2,10-dione Natural products CCC1OC(=O)C(C)C(O)C(C)C(O)C(C)CC(C)C(=O)C(C)C(O)C1C HQZOLNNEQAKEHT-UHFFFAOYSA-N 0.000 description 1
- 239000001075 (4R,4aR,8aS)-4,8a-dimethyl-1,2,3,4,5,6,7,8-octahydronaphthalen-4a-ol Substances 0.000 description 1
- HNSDLXPSAYFUHK-UHFFFAOYSA-N 1,4-bis(2-ethylhexyl) sulfosuccinate Chemical compound CCCCC(CC)COC(=O)CC(S(O)(=O)=O)C(=O)OCC(CC)CCCC HNSDLXPSAYFUHK-UHFFFAOYSA-N 0.000 description 1
- 101150029062 15 gene Proteins 0.000 description 1
- GFIBMQGRHYGHAP-UHFFFAOYSA-N 2-methyl-2-morpholin-4-ylpropan-1-amine Chemical compound NCC(C)(C)N1CCOCC1 GFIBMQGRHYGHAP-UHFFFAOYSA-N 0.000 description 1
- 101150098072 20 gene Proteins 0.000 description 1
- HQZOLNNEQAKEHT-IBBGRPSASA-N 6-deoxyerythronolide B Chemical compound CC[C@H]1OC(=O)[C@H](C)[C@@H](O)[C@H](C)[C@@H](O)[C@@H](C)C[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@H]1C HQZOLNNEQAKEHT-IBBGRPSASA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 102100022089 Acyl-[acyl-carrier-protein] hydrolase Human genes 0.000 description 1
- 241000576133 Alphasatellites Species 0.000 description 1
- 108091093088 Amplicon Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 101150076489 B gene Proteins 0.000 description 1
- 101100355997 Bacillus subtilis (strain 168) recA gene Proteins 0.000 description 1
- 0 C[C@@](C*C1)C1=*=CCC=*C=C Chemical compound C[C@@](C*C1)C1=*=CCC=*C=C 0.000 description 1
- 101100494265 Caenorhabditis elegans best-15 gene Proteins 0.000 description 1
- 101100167062 Caenorhabditis elegans chch-3 gene Proteins 0.000 description 1
- 241000192731 Chloroflexus aurantiacus Species 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 101710112752 Cytotoxin Proteins 0.000 description 1
- 102000012410 DNA Ligases Human genes 0.000 description 1
- 108010061982 DNA Ligases Proteins 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 241000255598 Drosophila mauritiana Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 102000004533 Endonucleases Human genes 0.000 description 1
- 101100301301 Escherichia coli (strain K12) recE gene Proteins 0.000 description 1
- 241001302160 Escherichia coli str. K-12 substr. DH10B Species 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 108010039731 Fatty Acid Synthases Proteins 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 241001135750 Geobacter Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 241000178946 Leptospira interrogans serovar Copenhageni Species 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 101150109417 NRPS gene Proteins 0.000 description 1
- 101150036369 NRPS2 gene Proteins 0.000 description 1
- 241000244206 Nematoda Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241001495390 Nocardioides sp. Species 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 241000309202 Pseudomonas stutzeri DSM 10701 Species 0.000 description 1
- 108700005075 Regulator Genes Proteins 0.000 description 1
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 1
- 108010019477 S-adenosyl-L-methionine-dependent N-methyltransferase Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 241001219473 Sepiola aurantica Species 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 108010012306 Tn5 transposase Proteins 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000016383 Zea mays subsp huehuetenangensis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 101150092394 argK gene Proteins 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 108010083912 bleomycin N-acetyltransferase Proteins 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 239000012159 carrier gas Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- 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 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000012411 cloning technique Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000013601 cosmid vector Substances 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 1
- JLPUXFOGCDVKGO-UHFFFAOYSA-N dl-geosmin Natural products C1CCCC2(O)C(C)CCCC21C JLPUXFOGCDVKGO-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000009483 enzymatic pathway Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 108010060641 flavanone synthetase Proteins 0.000 description 1
- -1 flaviolin compound Chemical class 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000012268 genome sequencing Methods 0.000 description 1
- 229930001467 geosmin Natural products 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 230000007446 host cell death Effects 0.000 description 1
- 238000000126 in silico method Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 238000009630 liquid culture Methods 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 235000009973 maize Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 150000002763 monocarboxylic acids Chemical class 0.000 description 1
- 101150081621 mtaB gene Proteins 0.000 description 1
- 231100000219 mutagenic Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229940037201 oris Drugs 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 108700010839 phage proteins Proteins 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 108010001814 phosphopantetheinyl transferase Proteins 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000019525 primary metabolic process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- QAQREVBBADEHPA-IEXPHMLFSA-N propionyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 QAQREVBBADEHPA-IEXPHMLFSA-N 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229930004725 sesquiterpene Natural products 0.000 description 1
- 150000004354 sesquiterpene derivatives Chemical class 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- VNOYUJKHFWYWIR-ITIYDSSPSA-N succinyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CCC(O)=O)O[C@H]1N1C2=NC=NC(N)=C2N=C1 VNOYUJKHFWYWIR-ITIYDSSPSA-N 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 101150061166 tetR gene Proteins 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229930184737 tubulysin Natural products 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 101150093896 xylS gene Proteins 0.000 description 1
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
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/14—Nitrogen or oxygen as hetero atom and at least one other diverse hetero ring atom in the same ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Oncology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0423755.8A GB0423755D0 (en) | 2004-10-26 | 2004-10-26 | Methods for heterologus expression of secondary metabolites |
| GB0423755.8 | 2004-10-26 | ||
| PCT/IB2005/003650 WO2006046152A2 (en) | 2004-10-26 | 2005-10-26 | Methods for heterologous expression of secondary metabolites |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2005298341A1 AU2005298341A1 (en) | 2006-05-04 |
| AU2005298341B2 true AU2005298341B2 (en) | 2011-06-23 |
Family
ID=33485231
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2005298341A Ceased AU2005298341B2 (en) | 2004-10-26 | 2005-10-26 | Methods for heterologous expression of secondary metabolites |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US20090298117A1 (enExample) |
| EP (1) | EP1809749B1 (enExample) |
| JP (1) | JP5566577B2 (enExample) |
| AT (1) | ATE422547T1 (enExample) |
| AU (1) | AU2005298341B2 (enExample) |
| CA (1) | CA2584777A1 (enExample) |
| DE (1) | DE602005012718D1 (enExample) |
| GB (1) | GB0423755D0 (enExample) |
| WO (1) | WO2006046152A2 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BRPI0605166A (pt) * | 2006-11-03 | 2008-07-01 | Inst Fleury | método de determinação de ácido metilmalÈnico baseado na extração alquilativa associada à cromatografia lìquida acoplada à espectrometria de massas |
| GB0922108D0 (en) | 2009-12-17 | 2010-02-03 | Gene Bridges Gmbh | Heterologous hosts |
| EP3027754B1 (en) | 2013-08-02 | 2022-03-02 | enEvolv, Inc. | Processes and host cells for genome, pathway, and biomolecular engineering |
| WO2017151059A1 (en) * | 2016-02-29 | 2017-09-08 | Agency For Science, Technology And Research | Multiplexable activation of silent biosynthetic clusters in native actinomycete hosts for natural product discovery |
| EP3938518A4 (en) | 2019-03-12 | 2023-01-11 | Terra Bioworks, Inc. | EXPRESSION VECTOR |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1291420B1 (en) * | 1997-12-05 | 2009-11-25 | Europäisches Laboratorium Für Molekularbiologie (Embl) | Novel DNA cloning method relying on the E.coli RECE/RECT recombination system |
| US6355412B1 (en) * | 1999-07-09 | 2002-03-12 | The European Molecular Biology Laboratory | Methods and compositions for directed cloning and subcloning using homologous recombination |
| JP2004508810A (ja) * | 2000-04-28 | 2004-03-25 | コーサン バイオサイエンシーズ， インコーポレイテッド | ポリケチドの生成 |
| WO2003044186A2 (en) * | 2001-11-22 | 2003-05-30 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Novel gene cluster of pederin biosynthesis genes |
| US20040005672A1 (en) * | 2002-02-22 | 2004-01-08 | Santi Daniel V. | Heterologous production of polyketides |
-
2004
- 2004-10-26 GB GBGB0423755.8A patent/GB0423755D0/en not_active Ceased
-
2005
- 2005-10-26 AT AT05810933T patent/ATE422547T1/de not_active IP Right Cessation
- 2005-10-26 US US11/577,972 patent/US20090298117A1/en not_active Abandoned
- 2005-10-26 EP EP05810933A patent/EP1809749B1/en not_active Expired - Lifetime
- 2005-10-26 AU AU2005298341A patent/AU2005298341B2/en not_active Ceased
- 2005-10-26 JP JP2007538549A patent/JP5566577B2/ja not_active Expired - Fee Related
- 2005-10-26 CA CA002584777A patent/CA2584777A1/en not_active Abandoned
- 2005-10-26 WO PCT/IB2005/003650 patent/WO2006046152A2/en not_active Ceased
- 2005-10-26 DE DE602005012718T patent/DE602005012718D1/de not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| WO2006046152A2 (en) | 2006-05-04 |
| AU2005298341A1 (en) | 2006-05-04 |
| JP5566577B2 (ja) | 2014-08-06 |
| EP1809749A2 (en) | 2007-07-25 |
| EP1809749B1 (en) | 2009-02-11 |
| CA2584777A1 (en) | 2006-05-04 |
| US20090298117A1 (en) | 2009-12-03 |
| DE602005012718D1 (de) | 2009-03-26 |
| WO2006046152A3 (en) | 2006-11-16 |
| GB0423755D0 (en) | 2004-11-24 |
| JP2008517996A (ja) | 2008-05-29 |
| ATE422547T1 (de) | 2009-02-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Song et al. | Enhanced heterologous spinosad production from a 79-kb synthetic multioperon assembly | |
| Pieper et al. | Cell-free synthesis of polyketides by recombinant erythromycin polyketide synthases | |
| US9181539B2 (en) | Strains for the production of flavonoids from glucose | |
| CN102015756B (zh) | Nrps-pks基因簇及其操纵和应用 | |
| JP2674998B2 (ja) | 抗生物質産生微生物の改良 | |
| Gao et al. | Mutations in genes encoding antibiotic substances increase the synthesis of poly‐γ‐glutamic acid in Bacillus amyloliquefaciens LL3 | |
| Ren et al. | Non-modular fatty acid synthases yield distinct N-terminal acylation in ribosomal peptides | |
| CN112375725B (zh) | 一种生产维生素b6的代谢工程菌株及其构建方法与应用 | |
| Liu et al. | A seamless and iterative DNA assembly method named PS-Brick and its assisted metabolic engineering for threonine and 1-propanol production | |
| AU2005298341B2 (en) | Methods for heterologous expression of secondary metabolites | |
| Zhang et al. | Simultaneous multiplex genome loci editing of Halomonas bluephagenesis using an engineered CRISPR-guided base editor | |
| US20020045220A1 (en) | Biosynthesis of polyketide synthase substrates | |
| Perlova et al. | Novel expression hosts for complex secondary metabolite megasynthetases: Production of myxochromide in the thermopilic isolate Corallococcus macrosporus GT-2 | |
| WO2002068613A1 (en) | Biosynthesis of polyketide synthase substrates | |
| Gillane et al. | Biosynthesis of novel non-proteinogenic amino acids β-hydroxyenduracididine and β-methylphenylalanine in Escherichia coli | |
| CN101962647B (zh) | 诺卡噻唑菌素的生物合成基因簇及其应用 | |
| WO2004015088A2 (en) | Transposon-based transformation system | |
| CN110551739A (zh) | 吡唑霉素生物合成基因簇、重组菌及其应用 | |
| CA2354030A1 (en) | Micromonospora echinospora genes encoding for biosynthesis of calicheamicin and self-resistance thereto | |
| WO2025140469A1 (en) | Bioengineering of modular polyketide synthases | |
| US20020192767A1 (en) | Biosynthesis of polyketide synthase substrates | |
| Walker | Mechanisms for the Generation of Structural Diversity in Polyketide Biosynthesis | |
| CN102516374A (zh) | 用于四霉素生物合成的蛋白系统及编码其的基因簇 | |
| Liu et al. | De novo biosynthesis of daptomycin through module construction and assembly in Escherichia coli | |
| Zhang et al. | High-Level Prodigiosin Production in Pseudomonas putida Enabled by Combinatorial Metabolic Engineering |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |