IL103076A - Bioprocess for preparing 7-aminodesacetoxy cephalosporanic acid - Google Patents

Bioprocess for preparing 7-aminodesacetoxy cephalosporanic acid

Info

Publication number: IL103076A
Authority: IL; Israel
Prior art keywords: adipoyl; adca; strain; apa; expandase
Prior art date: 1991-09-11

Application number

IL10307692A

Other languages

English (en)

Other versions

IL103076A0 (en

Original Assignee

Gist Brocades Bv

Priority date (The priority date 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 date listed.)

1991-09-11

Filing date

1992-09-07

Publication date

1996-10-31

1992-09-07 Application filed by Gist Brocades Bv filed Critical Gist Brocades Bv

1993-02-21 Publication of IL103076A0 publication Critical patent/IL103076A0/xx

1996-10-31 Publication of IL103076A publication Critical patent/IL103076A/en

Links

NVIAYEIXYQCDAN-CLZZGJSISA-N 7beta-aminodeacetoxycephalosporanic acid Chemical compound S1CC(C)=C(C(O)=O)N2C(=O)[C@@H](N)[C@@H]12 NVIAYEIXYQCDAN-CLZZGJSISA-N 0.000 title claims description 39
102000004190 Enzymes Human genes 0.000 claims abstract description 98
108090000790 Enzymes Proteins 0.000 claims abstract description 97
101710104123 Deacetoxycephalosporin C synthase Proteins 0.000 claims abstract description 93
241000228150 Penicillium chrysogenum Species 0.000 claims abstract description 57
108020004414 DNA Proteins 0.000 claims abstract description 55
230000000694 effects Effects 0.000 claims abstract description 41
125000003651 hexanedioyl group Chemical group C(CCCCC(=O)*)(=O)* 0.000 claims abstract description 39
108090000623 proteins and genes Proteins 0.000 claims abstract description 29
WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 claims abstract description 24
230000014509 gene expression Effects 0.000 claims abstract description 24
239000000758 substrate Substances 0.000 claims abstract description 22
239000001963 growth medium Substances 0.000 claims abstract description 20
238000004519 manufacturing process Methods 0.000 claims abstract description 18
MIFYHUACUWQUKT-UHFFFAOYSA-N Isopenicillin N Natural products OC(=O)C1C(C)(C)SC2C(NC(=O)CCCC(N)C(O)=O)C(=O)N21 MIFYHUACUWQUKT-UHFFFAOYSA-N 0.000 claims abstract description 17
230000012010 growth Effects 0.000 claims abstract description 16
150000003839 salts Chemical class 0.000 claims abstract description 16
WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 claims abstract description 14
239000001361 adipic acid Substances 0.000 claims abstract description 12
235000011037 adipic acid Nutrition 0.000 claims abstract description 12
239000013604 expression vector Substances 0.000 claims abstract description 12
238000011065 in-situ storage Methods 0.000 claims abstract description 12
150000002148 esters Chemical class 0.000 claims abstract description 11
108020004511 Recombinant DNA Proteins 0.000 claims abstract description 9
MIFYHUACUWQUKT-QSKNDCFUSA-N isopenicillin n Chemical compound OC(=O)[C@@H]1C(C)(C)S[C@H]2[C@H](NC(=O)CCC[C@H](N)C(O)=O)C(=O)N21 MIFYHUACUWQUKT-QSKNDCFUSA-N 0.000 claims abstract 4
238000000034 method Methods 0.000 claims description 48
239000013598 vector Substances 0.000 claims description 39
239000002609 medium Substances 0.000 claims description 21
239000013612 plasmid Substances 0.000 claims description 12
241000424942 Streptomyces clavuligerus ATCC 27064 Species 0.000 claims description 8
108091028043 Nucleic acid sequence Proteins 0.000 claims description 7
241000589516 Pseudomonas Species 0.000 claims description 7
101000981089 Streptomyces clavuligerus Deacetoxycephalosporin C synthase Proteins 0.000 claims description 4
238000012258 culturing Methods 0.000 claims description 4
KYKFCSHPTAVNJD-UHFFFAOYSA-L sodium adipate Chemical group [Na+].[Na+].[O-]C(=O)CCCCC([O-])=O KYKFCSHPTAVNJD-UHFFFAOYSA-L 0.000 claims description 4
235000011049 sodium adipate Nutrition 0.000 claims description 4
102000004169 proteins and genes Human genes 0.000 claims description 3
101000852577 Penicillium chrysogenum Isopenicillin N synthase Proteins 0.000 claims description 2
238000001727 in vivo Methods 0.000 claims 5
241000187433 Streptomyces clavuligerus Species 0.000 abstract description 13
239000002253 acid Substances 0.000 abstract description 6
101710095468 Cyclase Proteins 0.000 abstract description 2
229940088598 enzyme Drugs 0.000 description 92
238000000855 fermentation Methods 0.000 description 33
230000004151 fermentation Effects 0.000 description 33
239000012634 fragment Substances 0.000 description 25
239000000047 product Substances 0.000 description 25
230000009466 transformation Effects 0.000 description 24
241000228143 Penicillium Species 0.000 description 23
108700023418 Amidases Proteins 0.000 description 21
102000005922 amidase Human genes 0.000 description 21
229940124587 cephalosporin Drugs 0.000 description 21
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
239000000203 mixture Substances 0.000 description 20
229930186147 Cephalosporin Natural products 0.000 description 19
238000010276 construction Methods 0.000 description 18
150000001780 cephalosporins Chemical class 0.000 description 17
108010012172 isopenicillin N synthetase Proteins 0.000 description 17
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
210000004027 cell Anatomy 0.000 description 15
238000003776 cleavage reaction Methods 0.000 description 13
244000005700 microbiome Species 0.000 description 13
-1 penicillin compound Chemical class 0.000 description 13
230000007017 scission Effects 0.000 description 13
229920001817 Agar Polymers 0.000 description 12
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
239000008272 agar Substances 0.000 description 12
238000002955 isolation Methods 0.000 description 11
238000002703 mutagenesis Methods 0.000 description 11
231100000350 mutagenesis Toxicity 0.000 description 11
108091081024 Start codon Proteins 0.000 description 10
230000008569 process Effects 0.000 description 10
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
229930182555 Penicillin Natural products 0.000 description 9
238000006243 chemical reaction Methods 0.000 description 9
230000002255 enzymatic effect Effects 0.000 description 9
102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 9
108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 9
238000011534 incubation Methods 0.000 description 9
238000006049 ring expansion reaction Methods 0.000 description 9
QRBLKGHRWFGINE-UGWAGOLRSA-N 2-[2-[2-[[2-[[4-[[2-[[6-amino-2-[3-amino-1-[(2,3-diamino-3-oxopropyl)amino]-3-oxopropyl]-5-methylpyrimidine-4-carbonyl]amino]-3-[(2r,3s,4s,5s,6s)-3-[(2s,3r,4r,5s)-4-carbamoyl-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4,5-dihydroxy-6-(hydroxymethyl)- Chemical compound N=1C(C=2SC=C(N=2)C(N)=O)CSC=1CCNC(=O)C(C(C)=O)NC(=O)C(C)C(O)C(C)NC(=O)C(C(O[C@H]1[C@@]([C@@H](O)[C@H](O)[C@H](CO)O1)(C)O[C@H]1[C@@H]([C@](O)([C@@H](O)C(CO)O1)C(N)=O)O)C=1NC=NC=1)NC(=O)C1=NC(C(CC(N)=O)NCC(N)C(N)=O)=NC(N)=C1C QRBLKGHRWFGINE-UGWAGOLRSA-N 0.000 description 8
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 8
LTQCLFMNABRKSH-UHFFFAOYSA-N Phleomycin Natural products N=1C(C=2SC=C(N=2)C(N)=O)CSC=1CCNC(=O)C(C(O)C)NC(=O)C(C)C(O)C(C)NC(=O)C(C(OC1C(C(O)C(O)C(CO)O1)OC1C(C(OC(N)=O)C(O)C(CO)O1)O)C=1NC=NC=1)NC(=O)C1=NC(C(CC(N)=O)NCC(N)C(N)=O)=NC(N)=C1C LTQCLFMNABRKSH-UHFFFAOYSA-N 0.000 description 8
108010035235 Phleomycins Proteins 0.000 description 8
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 8
241000187747 Streptomyces Species 0.000 description 8
150000001413 amino acids Chemical class 0.000 description 8
238000005119 centrifugation Methods 0.000 description 8
239000008103 glucose Substances 0.000 description 8
LXJXRIRHZLFYRP-UHFFFAOYSA-N glyceraldehyde 3-phosphate Chemical compound O=CC(O)COP(O)(O)=O LXJXRIRHZLFYRP-UHFFFAOYSA-N 0.000 description 8
108091008146 restriction endonucleases Proteins 0.000 description 8
235000019333 sodium laurylsulphate Nutrition 0.000 description 8
239000000725 suspension Substances 0.000 description 8
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 7
108091034117 Oligonucleotide Proteins 0.000 description 7
241000228417 Sarocladium strictum Species 0.000 description 7
239000007983 Tris buffer Substances 0.000 description 7
229950008644 adicillin Drugs 0.000 description 7
238000003556 assay Methods 0.000 description 7
239000000872 buffer Substances 0.000 description 7
239000012153 distilled water Substances 0.000 description 7
238000011081 inoculation Methods 0.000 description 7
MIFYHUACUWQUKT-GPUHXXMPSA-N penicillin N Chemical group OC(=O)[C@H]1C(C)(C)S[C@@H]2[C@H](NC(=O)CCC[C@@H](N)C(O)=O)C(=O)N21 MIFYHUACUWQUKT-GPUHXXMPSA-N 0.000 description 7
239000000243 solution Substances 0.000 description 7
239000000126 substance Substances 0.000 description 7
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
XWCFYHBHOFBVIV-UHFFFAOYSA-N Deacetylcephalosporin C Natural products S1CC(CO)=C(C(O)=O)N2C(=O)C(NC(=O)CCCC(N)C(O)=O)C21 XWCFYHBHOFBVIV-UHFFFAOYSA-N 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 6
239000007984 Tris EDTA buffer Substances 0.000 description 6
229940024606 amino acid Drugs 0.000 description 6
XWCFYHBHOFBVIV-JWKOBGCHSA-N deacetylcephalosporin C Chemical compound S1CC(CO)=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CCC[C@@H](N)C(O)=O)[C@H]21 XWCFYHBHOFBVIV-JWKOBGCHSA-N 0.000 description 6
238000009585 enzyme analysis Methods 0.000 description 6
239000000543 intermediate Substances 0.000 description 6
MIFYHUACUWQUKT-GTQWGBSQSA-N isopenicillin N Chemical compound OC(=O)[C@H]1C(C)(C)S[C@@H]2[C@H](NC(=O)CCC[C@H](N)C(O)=O)C(=O)N21 MIFYHUACUWQUKT-GTQWGBSQSA-N 0.000 description 6
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 6
229940049954 penicillin Drugs 0.000 description 6
239000012071 phase Substances 0.000 description 6
150000002989 phenols Chemical class 0.000 description 6
238000003752 polymerase chain reaction Methods 0.000 description 6
239000000523 sample Substances 0.000 description 6
239000011780 sodium chloride Substances 0.000 description 6
NGHVIOIJCVXTGV-ALEPSDHESA-N 6-aminopenicillanic acid Chemical compound [O-]C(=O)[C@H]1C(C)(C)S[C@@H]2[C@H]([NH3+])C(=O)N21 NGHVIOIJCVXTGV-ALEPSDHESA-N 0.000 description 5
NGHVIOIJCVXTGV-UHFFFAOYSA-N 6beta-amino-penicillanic acid Natural products OC(=O)C1C(C)(C)SC2C(N)C(=O)N21 NGHVIOIJCVXTGV-UHFFFAOYSA-N 0.000 description 5
108010074633 Mixed Function Oxygenases Proteins 0.000 description 5
102000008109 Mixed Function Oxygenases Human genes 0.000 description 5
240000007594 Oryza sativa Species 0.000 description 5
235000007164 Oryza sativa Nutrition 0.000 description 5
108010087702 Penicillinase Proteins 0.000 description 5
239000011543 agarose gel Substances 0.000 description 5
AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 5
108010031946 deacetoxycephalosporin C hydroxylase Proteins 0.000 description 5
238000001962 electrophoresis Methods 0.000 description 5
101150073818 gap gene Proteins 0.000 description 5
238000004128 high performance liquid chromatography Methods 0.000 description 5
238000000338 in vitro Methods 0.000 description 5
229910000402 monopotassium phosphate Inorganic materials 0.000 description 5
239000008188 pellet Substances 0.000 description 5
229950009506 penicillinase Drugs 0.000 description 5
238000002360 preparation method Methods 0.000 description 5
235000009566 rice Nutrition 0.000 description 5
241000894007 species Species 0.000 description 5
238000011282 treatment Methods 0.000 description 5
108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
KMEMIMRPZGDOMG-UHFFFAOYSA-N 2-cyanoethoxyphosphonamidous acid Chemical compound NP(O)OCCC#N KMEMIMRPZGDOMG-UHFFFAOYSA-N 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
HOKIDJSKDBPKTQ-GLXFQSAKSA-N Cephalosporin C Natural products S1CC(COC(=O)C)=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CCC[C@@H](N)C(O)=O)[C@@H]12 HOKIDJSKDBPKTQ-GLXFQSAKSA-N 0.000 description 4
230000005526 G1 to G0 transition Effects 0.000 description 4
108010093096 Immobilized Enzymes Proteins 0.000 description 4
229930195708 Penicillin V Natural products 0.000 description 4
239000001888 Peptone Substances 0.000 description 4
108010080698 Peptones Proteins 0.000 description 4
102000004243 Tubulin Human genes 0.000 description 4
108090000704 Tubulin Proteins 0.000 description 4
238000004458 analytical method Methods 0.000 description 4
208000036815 beta tubulin Diseases 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
239000006227 byproduct Substances 0.000 description 4
229940041514 candida albicans extract Drugs 0.000 description 4
HOKIDJSKDBPKTQ-GLXFQSAKSA-M cephalosporin C(1-) Chemical compound S1CC(COC(=O)C)=C(C([O-])=O)N2C(=O)[C@@H](NC(=O)CCC[C@@H]([NH3+])C([O-])=O)[C@@H]12 HOKIDJSKDBPKTQ-GLXFQSAKSA-M 0.000 description 4
239000007795 chemical reaction product Substances 0.000 description 4
238000010828 elution Methods 0.000 description 4
238000005516 engineering process Methods 0.000 description 4
239000000284 extract Substances 0.000 description 4
238000000605 extraction Methods 0.000 description 4
238000001914 filtration Methods 0.000 description 4
PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 4
229910052757 nitrogen Inorganic materials 0.000 description 4
229940056367 penicillin v Drugs 0.000 description 4
235000019319 peptone Nutrition 0.000 description 4
BPLBGHOLXOTWMN-MBNYWOFBSA-N phenoxymethylpenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)COC1=CC=CC=C1 BPLBGHOLXOTWMN-MBNYWOFBSA-N 0.000 description 4
229920001223 polyethylene glycol Polymers 0.000 description 4
239000000376 reactant Substances 0.000 description 4
238000000926 separation method Methods 0.000 description 4
239000002904 solvent Substances 0.000 description 4
239000003643 water by type Substances 0.000 description 4
239000012138 yeast extract Substances 0.000 description 4
241000193830 Bacillus <bacterium> Species 0.000 description 3
102100031780 Endonuclease Human genes 0.000 description 3
108010042407 Endonucleases Proteins 0.000 description 3
241000588724 Escherichia coli Species 0.000 description 3
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
239000006137 Luria-Bertani broth Substances 0.000 description 3
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
240000008042 Zea mays Species 0.000 description 3
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 3
235000002017 Zea mays subsp mays Nutrition 0.000 description 3
238000002835 absorbance Methods 0.000 description 3
238000010564 aerobic fermentation Methods 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
230000000295 complement effect Effects 0.000 description 3
235000005822 corn Nutrition 0.000 description 3
NNQIJOYQWYKBOW-JWKOBGCHSA-N deacetoxycephalosporin C Chemical compound S1CC(C)=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CCC[C@@H](N)C(O)=O)[C@@H]12 NNQIJOYQWYKBOW-JWKOBGCHSA-N 0.000 description 3
238000011161 development Methods 0.000 description 3
230000018109 developmental process Effects 0.000 description 3
238000010790 dilution Methods 0.000 description 3
239000012895 dilution Substances 0.000 description 3
ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 3
229960005542 ethidium bromide Drugs 0.000 description 3
108010034416 glutarylamidocephalosporanic acid acylase Proteins 0.000 description 3
238000009396 hybridization Methods 0.000 description 3
239000004615 ingredient Substances 0.000 description 3
239000002054 inoculum Substances 0.000 description 3
230000003834 intracellular effect Effects 0.000 description 3
239000008101 lactose Substances 0.000 description 3
239000003550 marker Substances 0.000 description 3
230000037353 metabolic pathway Effects 0.000 description 3
238000012986 modification Methods 0.000 description 3
230000004048 modification Effects 0.000 description 3
229940056360 penicillin g Drugs 0.000 description 3
150000002960 penicillins Chemical class 0.000 description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
210000001938 protoplast Anatomy 0.000 description 3
238000000746 purification Methods 0.000 description 3
230000008929 regeneration Effects 0.000 description 3
238000011069 regeneration method Methods 0.000 description 3
238000012163 sequencing technique Methods 0.000 description 3
238000002741 site-directed mutagenesis Methods 0.000 description 3
239000006228 supernatant Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
238000011144 upstream manufacturing Methods 0.000 description 3
FZEVMBJWXHDLDB-ZCFIWIBFSA-N (6r)-5-thia-1-azabicyclo[4.2.0]oct-2-en-8-one Chemical group S1CC=CN2C(=O)C[C@H]21 FZEVMBJWXHDLDB-ZCFIWIBFSA-N 0.000 description 2
JPSKCQCQZUGWNM-UHFFFAOYSA-N 2,7-Oxepanedione Chemical compound O=C1CCCCC(=O)O1 JPSKCQCQZUGWNM-UHFFFAOYSA-N 0.000 description 2
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
TYMLOMAKGOJONV-UHFFFAOYSA-N 4-nitroaniline Chemical compound NC1=CC=C([N+]([O-])=O)C=C1 TYMLOMAKGOJONV-UHFFFAOYSA-N 0.000 description 2
FTMQFOCEVZLEJU-LURJTMIESA-N 6-[[(1S)-1-carboxy-2-hydroxyethyl]amino]-6-oxohexanoic acid Chemical compound C(CCCCC(=O)O)(=O)N[C@@H](CO)C(=O)O FTMQFOCEVZLEJU-LURJTMIESA-N 0.000 description 2
HSHGZXNAXBPPDL-HZGVNTEJSA-N 7beta-aminocephalosporanic acid Chemical compound S1CC(COC(=O)C)=C(C([O-])=O)N2C(=O)[C@@H]([NH3+])[C@@H]12 HSHGZXNAXBPPDL-HZGVNTEJSA-N 0.000 description 2
ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 2
ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
241000228245 Aspergillus niger Species 0.000 description 2
244000063299 Bacillus subtilis Species 0.000 description 2
241000589539 Brevundimonas diminuta Species 0.000 description 2
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
241001619326 Cephalosporium Species 0.000 description 2
108091026890 Coding region Proteins 0.000 description 2
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
239000003298 DNA probe Substances 0.000 description 2
CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
108700039691 Genetic Promoter Regions Proteins 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
238000010268 HPLC based assay Methods 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
229930195725 Mannitol Natural products 0.000 description 2
102000016943 Muramidase Human genes 0.000 description 2
108010014251 Muramidase Proteins 0.000 description 2
108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
241000589774 Pseudomonas sp. Species 0.000 description 2
240000004808 Saccharomyces cerevisiae Species 0.000 description 2
235000019764 Soybean Meal Nutrition 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
125000002252 acyl group Chemical group 0.000 description 2
229910052921 ammonium sulfate Inorganic materials 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
238000013459 approach Methods 0.000 description 2
239000011324 bead Substances 0.000 description 2
125000003460 beta-lactamyl group Chemical group 0.000 description 2
230000001588 bifunctional effect Effects 0.000 description 2
230000003115 biocidal effect Effects 0.000 description 2
239000001110 calcium chloride Substances 0.000 description 2
235000011148 calcium chloride Nutrition 0.000 description 2
229910001628 calcium chloride Inorganic materials 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
238000010367 cloning Methods 0.000 description 2
150000001875 compounds Chemical class 0.000 description 2
235000012343 cottonseed oil Nutrition 0.000 description 2
239000002385 cottonseed oil Substances 0.000 description 2
108010093176 deacetoxycephalosporin C synthetase Proteins 0.000 description 2
238000004520 electroporation Methods 0.000 description 2
230000002068 genetic effect Effects 0.000 description 2
238000010353 genetic engineering Methods 0.000 description 2
239000011521 glass Substances 0.000 description 2
239000012535 impurity Substances 0.000 description 2
230000010354 integration Effects 0.000 description 2
239000013067 intermediate product Substances 0.000 description 2
239000007788 liquid Substances 0.000 description 2
238000009630 liquid culture Methods 0.000 description 2
239000004325 lysozyme Substances 0.000 description 2
229960000274 lysozyme Drugs 0.000 description 2
235000010335 lysozyme Nutrition 0.000 description 2
230000002879 macerating effect Effects 0.000 description 2
230000014759 maintenance of location Effects 0.000 description 2
239000000594 mannitol Substances 0.000 description 2
235000010355 mannitol Nutrition 0.000 description 2
239000012528 membrane Substances 0.000 description 2
239000002207 metabolite Substances 0.000 description 2
239000002773 nucleotide Substances 0.000 description 2
125000003729 nucleotide group Chemical group 0.000 description 2
239000011591 potassium Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
238000011084 recovery Methods 0.000 description 2
238000011160 research Methods 0.000 description 2
238000012216 screening Methods 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000001601 sodium adipate Substances 0.000 description 2
239000001509 sodium citrate Substances 0.000 description 2
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
239000004455 soybean meal Substances 0.000 description 2
239000007858 starting material Substances 0.000 description 2
239000008223 sterile water Substances 0.000 description 2
238000003860 storage Methods 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
238000012360 testing method Methods 0.000 description 2
239000011573 trace mineral Substances 0.000 description 2
235000013619 trace mineral Nutrition 0.000 description 2
238000000844 transformation Methods 0.000 description 2
230000009105 vegetative growth Effects 0.000 description 2
238000003260 vortexing Methods 0.000 description 2
150000003952 β-lactams Chemical class 0.000 description 2
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
NKBWMBRPILTCRD-UHFFFAOYSA-N 2-Methylheptanoic acid Chemical compound CCCCCC(C)C(O)=O NKBWMBRPILTCRD-UHFFFAOYSA-N 0.000 description 1
MLONYBFKXHEPCD-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol Chemical compound OCC(N)(CO)CO.OCC(N)(CO)CO MLONYBFKXHEPCD-UHFFFAOYSA-N 0.000 description 1
FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
OPIFSICVWOWJMJ-AEOCFKNESA-N 5-bromo-4-chloro-3-indolyl beta-D-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CNC2=CC=C(Br)C(Cl)=C12 OPIFSICVWOWJMJ-AEOCFKNESA-N 0.000 description 1
241000228431 Acremonium chrysogenum Species 0.000 description 1
241000588986 Alcaligenes Species 0.000 description 1
241001558165 Alternaria sp. Species 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
241000187390 Amycolatopsis lactamdurans Species 0.000 description 1
235000017060 Arachis glabrata Nutrition 0.000 description 1
244000105624 Arachis hypogaea Species 0.000 description 1
235000010777 Arachis hypogaea Nutrition 0.000 description 1
235000018262 Arachis monticola Nutrition 0.000 description 1
241000186063 Arthrobacter Species 0.000 description 1
101000765308 Aspergillus niger N-(5'-phosphoribosyl)anthranilate isomerase Proteins 0.000 description 1
241000228257 Aspergillus sp. Species 0.000 description 1
241000894006 Bacteria Species 0.000 description 1
241000193417 Brevibacillus laterosporus Species 0.000 description 1
241000186146 Brevibacterium Species 0.000 description 1
241000721584 Brevundimonas bullata Species 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
101100136727 Caenorhabditis elegans psd-1 gene Proteins 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
241000135254 Cephalosporium sp. Species 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
108020004705 Codon Proteins 0.000 description 1
102000018832 Cytochromes Human genes 0.000 description 1
108010052832 Cytochromes Proteins 0.000 description 1
108090000204 Dipeptidase 1 Proteins 0.000 description 1
QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
101150013191 E gene Proteins 0.000 description 1
241000190562 Emericellopsis Species 0.000 description 1
108010067770 Endopeptidase K Proteins 0.000 description 1
229920001917 Ficoll Polymers 0.000 description 1
241000589565 Flavobacterium Species 0.000 description 1
241000589564 Flavobacterium sp. Species 0.000 description 1
108020004206 Gamma-glutamyltransferase Proteins 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
OYIFNHCXNCRBQI-BYPYZUCNSA-N L-2-aminoadipic acid Chemical compound OC(=O)[C@@H](N)CCCC(O)=O OYIFNHCXNCRBQI-BYPYZUCNSA-N 0.000 description 1
239000004201 L-cysteine Substances 0.000 description 1
235000013878 L-cysteine Nutrition 0.000 description 1
108090000364 Ligases Proteins 0.000 description 1
102000003960 Ligases Human genes 0.000 description 1
239000006142 Luria-Bertani Agar Substances 0.000 description 1
241001531966 Lysobacter lactamgenus Species 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
238000005481 NMR spectroscopy Methods 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
239000000020 Nitrocellulose Substances 0.000 description 1
108700026244 Open Reading Frames Proteins 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
108010073038 Penicillin Amidase Proteins 0.000 description 1
101000847770 Penicillium chrysogenum N-(5'-phosphoribosyl)anthranilate isomerase Proteins 0.000 description 1
102000007079 Peptide Fragments Human genes 0.000 description 1
108010033276 Peptide Fragments Proteins 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
241000588777 Providencia rettgeri Species 0.000 description 1
241000015473 Schizothorax griseus Species 0.000 description 1
241000122799 Scopulariopsis Species 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
241000203644 Streptoalloteichus hindustanus Species 0.000 description 1
241001147855 Streptomyces cattleya Species 0.000 description 1
241000936757 Streptomyces filipinensis Species 0.000 description 1
241000913723 Streptomyces heteromorphus Species 0.000 description 1
241000913724 Streptomyces panayensis Species 0.000 description 1
241001248020 Streptomyces wadayamensis Species 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
239000004098 Tetracycline Substances 0.000 description 1
JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
230000003213 activating effect Effects 0.000 description 1
150000001278 adipic acid derivatives Chemical class 0.000 description 1
230000002411 adverse Effects 0.000 description 1
238000000246 agarose gel electrophoresis Methods 0.000 description 1
108010049411 alpha-aminoadipyl-cysteinyl-valine synthetase Proteins 0.000 description 1
125000000539 amino acid group Chemical group 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
229960004050 aminobenzoic acid Drugs 0.000 description 1
BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
235000011130 ammonium sulphate Nutrition 0.000 description 1
229940072049 amyl acetate Drugs 0.000 description 1
PGMYKACGEOXYJE-UHFFFAOYSA-N anhydrous amyl acetate Natural products CCCCCOC(C)=O PGMYKACGEOXYJE-UHFFFAOYSA-N 0.000 description 1
JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
229940072107 ascorbate Drugs 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
230000001580 bacterial effect Effects 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
108010005774 beta-Galactosidase Proteins 0.000 description 1
102000006635 beta-lactamase Human genes 0.000 description 1
108091008324 binding proteins Proteins 0.000 description 1
238000004166 bioassay Methods 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
239000004327 boric acid Substances 0.000 description 1
239000006172 buffering agent Substances 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
244000309466 calf Species 0.000 description 1
101150091913 cefE gene Proteins 0.000 description 1
239000006285 cell suspension Substances 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 description 1
229940106164 cephalexin Drugs 0.000 description 1
150000001782 cephems Chemical group 0.000 description 1
235000013339 cereals Nutrition 0.000 description 1
238000012512 characterization method Methods 0.000 description 1
238000001311 chemical methods and process Methods 0.000 description 1
238000004737 colorimetric analysis Methods 0.000 description 1
238000012790 confirmation Methods 0.000 description 1
239000000356 contaminant Substances 0.000 description 1
229910000366 copper(II) sulfate Inorganic materials 0.000 description 1
RGWHQCVHVJXOKC-SHYZEUOFSA-J dCTP(4-) Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)C1 RGWHQCVHVJXOKC-SHYZEUOFSA-J 0.000 description 1
238000009795 derivation Methods 0.000 description 1
NNQIJOYQWYKBOW-UHFFFAOYSA-N desacetoxycephalosphorin G Natural products S1CC(C)=C(C(O)=O)N2C(=O)C(NC(=O)CCCC(N)C(O)=O)C12 NNQIJOYQWYKBOW-UHFFFAOYSA-N 0.000 description 1
238000000502 dialysis Methods 0.000 description 1
150000008049 diazo compounds Chemical class 0.000 description 1
FFYPMLJYZAEMQB-UHFFFAOYSA-N diethyl pyrocarbonate Chemical compound CCOC(=O)OC(=O)OCC FFYPMLJYZAEMQB-UHFFFAOYSA-N 0.000 description 1
238000009792 diffusion process Methods 0.000 description 1
AIUDWMLXCFRVDR-UHFFFAOYSA-N dimethyl 2-(3-ethyl-3-methylpentyl)propanedioate Chemical class CCC(C)(CC)CCC(C(=O)OC)C(=O)OC AIUDWMLXCFRVDR-UHFFFAOYSA-N 0.000 description 1
235000021186 dishes Nutrition 0.000 description 1
239000003814 drug Substances 0.000 description 1
230000007071 enzymatic hydrolysis Effects 0.000 description 1
238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
238000006911 enzymatic reaction Methods 0.000 description 1
238000001952 enzyme assay Methods 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000012467 final product Substances 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
230000002538 fungal effect Effects 0.000 description 1
230000004927 fusion Effects 0.000 description 1
102000006640 gamma-Glutamyltransferase Human genes 0.000 description 1
239000011491 glass wool Substances 0.000 description 1
125000001475 halogen functional group Chemical group 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
229960002897 heparin Drugs 0.000 description 1
229920000669 heparin Polymers 0.000 description 1
MNWFXJYAOYHMED-UHFFFAOYSA-M heptanoate Chemical compound CCCCCCC([O-])=O MNWFXJYAOYHMED-UHFFFAOYSA-M 0.000 description 1
230000006872 improvement Effects 0.000 description 1
230000002779 inactivation Effects 0.000 description 1
238000011835 investigation Methods 0.000 description 1
238000004255 ion exchange chromatography Methods 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
238000002372 labelling Methods 0.000 description 1
239000010699 lard oil Substances 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
238000013507 mapping Methods 0.000 description 1
235000012054 meals Nutrition 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
230000000813 microbial effect Effects 0.000 description 1
230000002906 microbiologic effect Effects 0.000 description 1
235000013379 molasses Nutrition 0.000 description 1
125000000896 monocarboxylic acid group Chemical group 0.000 description 1
235000019796 monopotassium phosphate Nutrition 0.000 description 1
LPUQAYUQRXPFSQ-DFWYDOINSA-M monosodium L-glutamate Chemical compound [Na+].[O-]C(=O)[C@@H](N)CCC(O)=O LPUQAYUQRXPFSQ-DFWYDOINSA-M 0.000 description 1
235000013923 monosodium glutamate Nutrition 0.000 description 1
239000004223 monosodium glutamate Substances 0.000 description 1
239000004570 mortar (masonry) Substances 0.000 description 1
239000006225 natural substrate Substances 0.000 description 1
229920001220 nitrocellulos Polymers 0.000 description 1
235000015097 nutrients Nutrition 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
235000020232 peanut Nutrition 0.000 description 1
229940066779 peptones Drugs 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
238000013492 plasmid preparation Methods 0.000 description 1
239000013600 plasmid vector Substances 0.000 description 1
235000011056 potassium acetate Nutrition 0.000 description 1
GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
LWIHDJKSTIGBAC-UHFFFAOYSA-K potassium phosphate Substances [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
238000010188 recombinant method Methods 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
239000011369 resultant mixture Substances 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
239000004576 sand Substances 0.000 description 1
235000020183 skimmed milk Nutrition 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
229940083575 sodium dodecyl sulfate Drugs 0.000 description 1
QPILZZVXGUNELN-UHFFFAOYSA-M sodium;4-amino-5-hydroxynaphthalene-2,7-disulfonate;hydron Chemical class [Na+].OS(=O)(=O)C1=CC(O)=C2C(N)=CC(S([O-])(=O)=O)=CC2=C1 QPILZZVXGUNELN-UHFFFAOYSA-M 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
230000002194 synthesizing effect Effects 0.000 description 1
229960002180 tetracycline Drugs 0.000 description 1
229930101283 tetracycline Natural products 0.000 description 1
235000019364 tetracycline Nutrition 0.000 description 1
150000003522 tetracyclines Chemical class 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
210000001541 thymus gland Anatomy 0.000 description 1
230000001131 transforming effect Effects 0.000 description 1
238000013519 translation Methods 0.000 description 1
239000012137 tryptone Substances 0.000 description 1
238000002211 ultraviolet spectrum Methods 0.000 description 1
229960004295 valine Drugs 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/52—Genes encoding for enzymes or proenzymes
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/0004—Oxidoreductases (1.)
- C12N9/0071—Oxidoreductases (1.) acting on paired donors with incorporation of molecular oxygen (1.14)
- 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
- C12P35/00—Preparation of compounds having a 5-thia-1-azabicyclo [4.2.0] octane ring system, e.g. cephalosporin
- 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
- C12P35/00—Preparation of compounds having a 5-thia-1-azabicyclo [4.2.0] octane ring system, e.g. cephalosporin
- C12P35/02—Preparation of compounds having a 5-thia-1-azabicyclo [4.2.0] octane ring system, e.g. cephalosporin by desacylation of the substituent in the 7 position
- 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
- C12P37/00—Preparation of compounds having a 4-thia-1-azabicyclo [3.2.0] heptane ring system, e.g. penicillin
- C12P37/04—Preparation of compounds having a 4-thia-1-azabicyclo [3.2.0] heptane ring system, e.g. penicillin by acylation of the substituent in the 6 position
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/8215—Microorganisms
- Y10S435/911—Microorganisms using fungi
- Y10S435/933—Penicillium
- Y10S435/935—Penicillium chrysogenum

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Health & Medical Sciences (AREA)
Zoology (AREA)
Wood Science & Technology (AREA)
Genetics & Genomics (AREA)
Bioinformatics & Cheminformatics (AREA)
Biotechnology (AREA)
General Engineering & Computer Science (AREA)
Microbiology (AREA)
General Health & Medical Sciences (AREA)
Biochemistry (AREA)
Biomedical Technology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Molecular Biology (AREA)
Medicinal Chemistry (AREA)
Plant Pathology (AREA)
Biophysics (AREA)
Physics & Mathematics (AREA)
Micro-Organisms Or Cultivation Processes Thereof (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Enzymes And Modification Thereof (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Cephalosporin Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Saccharide Compounds (AREA)

IL10307692A 1991-09-11 1992-09-07 Bioprocess for preparing 7-aminodesacetoxy cephalosporanic acid IL103076A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US75787991A	1991-09-11	1991-09-11
US07/933,469 US5318896A (en)	1991-09-11	1992-08-28	Recombinant expandase bioprocess for preparing 7-aminodesacetoxy cephalosporanic acid (7-ADCA)

Publications (2)

Publication Number	Publication Date
IL103076A0 IL103076A0 (en)	1993-02-21
IL103076A true IL103076A (en)	1996-10-31

Family

ID=27116462

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL10307692A IL103076A (en)	1991-09-11	1992-09-07	Bioprocess for preparing 7-aminodesacetoxy cephalosporanic acid

Country Status (25)

Country	Link
US (1)	US5318896A (fr)
EP (2)	EP0532341B1 (fr)
JP (2)	JP3027847B2 (fr)
KR (2)	KR940702544A (fr)
CN (2)	CN1066488C (fr)
AT (1)	ATE173017T1 (fr)
AU (1)	AU657787B2 (fr)
BG (1)	BG62177B1 (fr)
CA (1)	CA2077921C (fr)
CZ (1)	CZ287357B6 (fr)
DE (1)	DE69227494T2 (fr)
DK (1)	DK0532341T3 (fr)
ES (1)	ES2126588T3 (fr)
FI (1)	FI108148B (fr)
HU (1)	HU217171B (fr)
IL (1)	IL103076A (fr)
MX (1)	MX9205175A (fr)
NO (1)	NO316742B1 (fr)
NZ (1)	NZ244236A (fr)
RO (1)	RO115886B1 (fr)
RU (1)	RU2178808C2 (fr)
SK (1)	SK282387B6 (fr)
TW (1)	TW270149B (fr)
UA (1)	UA41292C2 (fr)
WO (1)	WO1993005158A1 (fr)

Families Citing this family (36)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3789880T2 (de) *	1986-01-31	1994-09-08	Beecham Group Plc	Isolierung und Expression von bei der Biosynthese von Beta-Laktamen beteiligten Genen.
US6709859B1 (en)	1986-01-31	2004-03-23	Beecham Group P.L.C.	Chromosomal DNA Fragments Encoding Enzymes for Encoding B-Lactam Biosynthesis Enzymes, and Vector and Transformants for Their Expression
KR100227711B1 (ko) *	1991-10-15	1999-12-01	한스 발터 라벤	7-아미노세팔로스포란산 및 7-아미노데아세틸세팔로스포란산 제조를 위한 신규한 생물학적 공정
ES2194873T3 (es) *	1993-07-30	2003-12-01	Dsm Ip Assets Bv	Procedimiento para la produccion eficaz de 7-adca a traves de 3-(carboxietil)propionil-7-adca.
RU2139350C1 (ru) *	1993-07-30	1999-10-10	Гист-Брокейдс Б.В.	Способ эффективного производства 7-адцк через 3-(карбоксиэтилтио)пропионил-7-адцк
RU2139349C1 (ru) *	1993-07-30	1999-10-10	Гист-Брокейдс Б.В.	Способ эффективного производства 7-адцк через 2-(карбоксиэтилтио) ацетил-7-адцк и 3-(карбоксиметилтио)пропионил-7-адцк
BR9407108A (pt) *	1993-07-30	1996-08-27	Gist Brocades Nv	Processo para a preparação e recuperação de ácido 7-amino desacetoxi cefalosporânico (7-adca) vetor de ADN recombinante e célula hospedeira transformada com um vetor definido
US5731165A (en) *	1995-06-02	1998-03-24	Gist-Brocades, B.V.	Process for the production of 7-ADCA via expandase activity on penicillin G
GB2323361A (en) *	1995-11-27	1998-09-23	Gist Brocades Bv	Improved process for the production of semi-synthetic cephalosporins via expandase activity on penicillin G
WO1997038107A1 (fr) *	1996-04-04	1997-10-16	Gist-Brocades B.V.	Enzyme possedant une forte activite d'adipoyl-coenzyme a synthetase et utilisations de celle-ci
WO1998000382A1 (fr)	1996-07-02	1998-01-08	Toray Industries, Inc.	Procedes de preparation de cetones optiquement actives
EP0914463A2 (fr)	1996-07-16	1999-05-12	Gist-Brocades B.V.	NOUVEAU PROCEDE DE PRODUCTION DE CEPHALOSPORINES A L'AIDE D'$i(ACREMONIUM CHRYSOGENUM)
CZ299290B6 (cs) *	1997-02-20	2008-06-11	Dsm Ip Assets B.V.	Zpusob výroby beta-laktamové slouceniny, zpusob prípravy a/nebo zlepšení vláknitého mikrobiálního kmene a použití chemicky definovaného fermentacníhomédia
PL330760A1 (en) *	1997-04-22	1999-05-24	Gist Brocades Bv	Method of obatining decylated cephalosporins by fermentation process
KR20000022108A (ko) *	1997-04-22	2000-04-25	한스 발터 라벤	탈아실화된 세팔로스포린의 발효제조방법
US6319684B1 (en)	1997-04-22	2001-11-20	Dms N.V.	Process for the fermentative production of cephalosporin
WO1998048037A1 (fr) *	1997-04-22	1998-10-29	Dsm N.V.	Procede de regulation de la solubilite d'une betalactamine
EP0918879A1 (fr) *	1997-04-22	1999-06-02	Gist-Brocades B.V.	Procede de preparation d'une betalactamine
WO1999033994A1 (fr) *	1997-12-24	1999-07-08	Isis Innovation Limited	Desacetoxycephalosporine c synthase (daocs) modifies et structure aux rayons x
ATE226954T1 (de) *	1998-03-27	2002-11-15	Dsm Nv	Verfahren zur fermentativen herstellung von cephalosporin
US6383773B2 (en)	1998-04-23	2002-05-07	Massachusetts Institute Of Technology	Penicillin conversion
CN100390285C (zh) *	1998-05-19	2008-05-28	Dsm公司	体内生产头孢菌素的改良
ES2165276B1 (es) *	1999-06-18	2003-03-01	Antibioticos Sau	Procedimiento biotecnologico para la produccion de acido 7-aminocefal osporanico (7-adca) y compuestos de sintesis intermedios particularmente penicilina n y desacetoxicefalosporina c (daoc)
IL152643A0 (en)	2000-05-13	2003-06-24	Smithkline Beecham Plc	Process for the purification of a salt of clavulanic acid
EP1974029A2 (fr)	2005-12-28	2008-10-01	DSMIP Assets B.V.	Acylases mutantes
CN101389635B (zh) *	2006-02-23	2013-03-06	中化帝斯曼制药有限公司荷兰公司	改进的头孢菌素生产
EP2123772A1 (fr)	2008-04-29	2009-11-25	DSM IP Assets B.V.	Souches produisant des antibiotiques bêta-lactamines
CN102131917A (zh) *	2008-08-05	2011-07-20	帝斯曼知识产权资产管理有限公司	生产己二酰基-7-adca的菌株
EP2310488B1 (fr) *	2008-08-05	2012-09-19	DSM Sinochem Pharmaceuticals Netherlands B.V.	Souches produisant de l'adipoyl-7-adca
EP2310487A2 (fr)	2008-08-05	2011-04-20	DSM IP Assets B.V.	Souches productrices d'adipoyl-7-adca
CN102369290A (zh)	2009-04-03	2012-03-07	帝斯曼知识产权资产管理有限公司	发酵工艺
WO2011161004A1 (fr)	2010-06-22	2011-12-29	Dsm Ip Assets B.V.	Procédé de fermentation à bulles d'air
EP2614066B1 (fr)	2010-09-07	2017-11-29	DSM Sinochem Pharmaceuticals Netherlands B.V.	Procédé de production de céphalosporines
WO2012117038A1 (fr)	2011-03-03	2012-09-07	Dsm Sinochem Pharmaceuticals Netherlands B.V.	Dégradation de composés de pénicilline
WO2015091455A1 (fr)	2013-12-17	2015-06-25	Dpx Holdings B.V.	Bioréacteur
CN113699209B (zh) *	2021-08-30	2023-05-02	浙江昂利康制药股份有限公司	一种7-adca回收方法

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR1270852A (fr) *	1960-09-20	1961-09-01	Bayer Ag	Procédé d'acylation enzymatique d'acide 6-aminopénicillanique
DE3789880T2 (de) *	1986-01-31	1994-09-08	Beecham Group Plc	Isolierung und Expression von bei der Biosynthese von Beta-Laktamen beteiligten Genen.
IL81555A0 (en) *	1986-11-17	1987-09-16	Baldwin Jack Edward	Enzymatic process for 3-substituted cephalosporins
ATE90382T1 (de) *	1987-01-17	1993-06-15	Hoechst Ag	Verwendung von gamma-glutamyl-transpeptidase.
US5070020A (en) *	1988-05-09	1991-12-03	Eli Lilly And Company	Recombinant dna expression vectors and dna compounds that encode deacetoxycephalosporin c synthetase
US5108918A (en) *	1988-08-11	1992-04-28	Gist-Brocades	Method for identifying and using biosynthetic genes for enhanced production of secondary metabolites
IL95766A (en) *	1989-09-27	1996-12-05	Lilly Co Eli	Recombinant DNA expression vectors And DNA compounds. Which encode Aspergillus acyltransferase activity
KR0171897B1 (ko) *	1989-12-27	1999-02-01	후지사와 도모끼찌로	7-아미노세펨 화합물 또는 그 염류의 제조 방법
KR100227711B1 (ko) *	1991-10-15	1999-12-01	한스 발터 라벤	7-아미노세팔로스포란산 및 7-아미노데아세틸세팔로스포란산 제조를 위한 신규한 생물학적 공정

1992
- 1992-08-28 US US07/933,469 patent/US5318896A/en not_active Expired - Lifetime
- 1992-09-07 NZ NZ244236A patent/NZ244236A/en not_active IP Right Cessation
- 1992-09-07 IL IL10307692A patent/IL103076A/en not_active IP Right Cessation
- 1992-09-10 MX MX9205175A patent/MX9205175A/es unknown
- 1992-09-10 CA CA002077921A patent/CA2077921C/fr not_active Expired - Fee Related
- 1992-09-10 CN CN92112278A patent/CN1066488C/zh not_active Expired - Lifetime
- 1992-09-11 RU RU94017674/13A patent/RU2178808C2/ru not_active IP Right Cessation
- 1992-09-11 AT AT92308286T patent/ATE173017T1/de not_active IP Right Cessation
- 1992-09-11 UA UA94005434A patent/UA41292C2/uk unknown
- 1992-09-11 AU AU23542/92A patent/AU657787B2/en not_active Ceased
- 1992-09-11 KR KR1019940700777A patent/KR940702544A/ko active Granted
- 1992-09-11 EP EP92308286A patent/EP0532341B1/fr not_active Expired - Lifetime
- 1992-09-11 JP JP5505516A patent/JP3027847B2/ja not_active Expired - Fee Related
- 1992-09-11 WO PCT/US1992/007711 patent/WO1993005158A1/fr not_active Ceased
- 1992-09-11 ES ES92308286T patent/ES2126588T3/es not_active Expired - Lifetime
- 1992-09-11 DE DE69227494T patent/DE69227494T2/de not_active Expired - Fee Related
- 1992-09-11 SK SK288-94A patent/SK282387B6/sk unknown
- 1992-09-11 CZ CZ1994532A patent/CZ287357B6/cs not_active IP Right Cessation
- 1992-09-11 DK DK92308286T patent/DK0532341T3/da active
- 1992-09-11 EP EP97203374A patent/EP0843013A3/fr not_active Withdrawn
- 1992-09-11 KR KR1019940700777A patent/KR0132440B1/ko not_active Expired - Fee Related
- 1992-09-11 HU HU9400715A patent/HU217171B/hu not_active IP Right Cessation
- 1992-09-11 RO RO94-00380A patent/RO115886B1/ro unknown
- 1992-09-19 TW TW081107399A patent/TW270149B/zh active
1994
- 1994-03-09 BG BG98643A patent/BG62177B1/bg unknown
- 1994-03-10 FI FI941135A patent/FI108148B/fi active
- 1994-03-10 NO NO19940848A patent/NO316742B1/no unknown
1999
- 1999-08-26 JP JP11239731A patent/JP3072101B2/ja not_active Expired - Fee Related
2000
- 2000-08-31 CN CN00126889A patent/CN1332247A/zh active Pending

Also Published As

Publication number	Publication date
HU9400715D0 (en)	1994-06-28
CN1066488C (zh)	2001-05-30
JP3072101B2 (ja)	2000-07-31
MX9205175A (es)	1994-02-28
KR0132440B1 (ko)	1998-04-14
US5318896A (en)	1994-06-07
SK282387B6 (sk)	2002-01-07
EP0843013A2 (fr)	1998-05-20
BG98643A (bg)	1995-03-31
BG62177B1 (bg)	1999-04-30
WO1993005158A1 (fr)	1993-03-18
CA2077921C (fr)	1998-11-24
CN1075336A (zh)	1993-08-18
RO115886B1 (ro)	2000-07-28
EP0532341A1 (fr)	1993-03-17
ES2126588T3 (es)	1999-04-01
IL103076A0 (en)	1993-02-21
TW270149B (fr)	1996-02-11
KR940702544A (ko)	1994-08-20
DK0532341T3 (da)	1999-07-19
NO940848L (no)	1994-03-10
CZ287357B6 (cs)	2000-11-15
EP0843013A3 (fr)	1998-06-17
NO940848D0 (no)	1994-03-10
AU2354292A (en)	1993-03-18
EP0532341B1 (fr)	1998-11-04
FI941135A0 (fi)	1994-03-10
NO316742B1 (no)	2004-04-26
HU217171B (hu)	1999-12-28
SK28894A3 (en)	1994-09-07
AU657787B2 (en)	1995-03-23
FI941135L (fi)	1994-03-10
NZ244236A (en)	1994-03-25
CN1332247A (zh)	2002-01-23
ATE173017T1 (de)	1998-11-15
FI108148B (fi)	2001-11-30
JP3027847B2 (ja)	2000-04-04
DE69227494D1 (de)	1998-12-10
JP2000060582A (ja)	2000-02-29
JPH07501931A (ja)	1995-03-02
RU2178808C2 (ru)	2002-01-27
CA2077921A1 (fr)	1993-03-12
CZ53294A3 (en)	1994-08-17
DE69227494T2 (de)	1999-04-08
UA41292C2 (uk)	2001-09-17
HUT69801A (en)	1995-09-28

Legal Events

Date	Code	Title
1997-03-18	FF	Patent granted
1997-07-13	KB	Patent renewed
1999-01-26	KB	Patent renewed
2000-06-01	HP	Change in proprietorship
2006-10-30	KB	Patent renewed
2011-04-28	MM9K	Patent not in force due to non-payment of renewal fees

Publication	Publication Date	Title
AU657787B2 (en)	1995-03-23	Novel bioprocess for preparing 7-ADCA
US5559005A (en)	1996-09-24	Bioprocess for preparing 7-ACA and 7-ADAC
RU2202616C2 (ru)	2003-04-20	Способ получения 7-аминоцефалоспорановой кислоты, вектор экспрессии, рекомбинантный штамм
PL174984B1 (pl)	1998-10-30	Nowy proces biologiczny wytwarzania kwasu 7-aminodezacetoksycefalosporanowego (kwasu 7-ADC)
PL172155B1 (pl)	1997-08-29	Sposób biotechnologiczny wytwarzania pochodnych kwasu cefalosporanowego