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
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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
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PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
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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
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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
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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
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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
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240000007594 Oryza sativa Species 0.000 description 5
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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
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101150073818 gap gene Proteins 0.000 description 5
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KMEMIMRPZGDOMG-UHFFFAOYSA-N 2-cyanoethoxyphosphonamidous acid Chemical compound NP(O)OCCC#N KMEMIMRPZGDOMG-UHFFFAOYSA-N 0.000 description 4
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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
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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
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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
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KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
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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
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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

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Wood Science & Technology (AREA)
Zoology (AREA)
Health & Medical Sciences (AREA)
Genetics & Genomics (AREA)
Bioinformatics & Cheminformatics (AREA)
Biotechnology (AREA)
General Engineering & Computer Science (AREA)
General Health & Medical Sciences (AREA)
Biochemistry (AREA)
Microbiology (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Biomedical Technology (AREA)
Molecular Biology (AREA)
Medicinal Chemistry (AREA)
Biophysics (AREA)
Physics & Mathematics (AREA)
Plant Pathology (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)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Cephalosporin Compounds (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 (de)
EP (2)	EP0843013A3 (de)
JP (2)	JP3027847B2 (de)
KR (2)	KR940702544A (de)
CN (2)	CN1066488C (de)
AT (1)	ATE173017T1 (de)
AU (1)	AU657787B2 (de)
BG (1)	BG62177B1 (de)
CA (1)	CA2077921C (de)
CZ (1)	CZ287357B6 (de)
DE (1)	DE69227494T2 (de)
DK (1)	DK0532341T3 (de)
ES (1)	ES2126588T3 (de)
FI (1)	FI108148B (de)
HU (1)	HU217171B (de)
IL (1)	IL103076A (de)
MX (1)	MX9205175A (de)
NO (1)	NO316742B1 (de)
NZ (1)	NZ244236A (de)
RO (1)	RO115886B1 (de)
RU (1)	RU2178808C2 (de)
SK (1)	SK282387B6 (de)
TW (1)	TW270149B (de)
UA (1)	UA41292C2 (de)
WO (1)	WO1993005158A1 (de)

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DE3789880T2 (de) *	1986-01-31	1994-09-08	Beecham Group Plc	Isolierung und Expression von bei der Biosynthese von Beta-Laktamen beteiligten Genen.
SK280569B6 (sk) *	1991-10-15	2000-03-13	Gist-Brocades B.V.	Biologický spôsob výroby kyseliny7-aminodeacetylce
PT711348E (pt) *	1993-07-30	2003-08-29	Dsm Nv	Processo para a eficiente producao de 7-adca por via de 3-(carboxietiltio)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
KR100336174B1 (ko) *	1993-07-30	2002-11-01	디에스엠 기스트 베.파우.	2-(카르복시에틸티오)아세틸-7-adca및3-(카르복시메틸티오)프로피오닐-7-adca를경유하여7-adca를제조하는효율적인방법
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
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
EP0863989A2 (de) *	1995-11-27	1998-09-16	Gist-Brocades B.V.	Verbessertes verfahren zur herstellung von halb-synthetischen cephalosporinen mittels einer auf penicilin g wirkenden expandaseaktivität
WO1997038107A1 (en) *	1996-04-04	1997-10-16	Gist-Brocades B.V.	An enzyme with high adipoyl-coenzyme a synthetase activity and uses thereof
US6320069B1 (en)	1996-07-02	2001-11-20	Toray Industries, Inc.	Production of optically active ketone
AU4201897A (en)	1996-07-16	1998-02-09	Gist-Brocades B.V.	Novel process for the preparation of cephalosporins using (acremonium chrysogenum)
PL335227A1 (en) *	1997-02-20	2000-04-10	Dsm Nv	Industrial-scale production of valuable compounds by fermentation in a chemically defined medium
BR9804858A (pt) *	1997-04-22	1999-08-24	Gist Brocades Bv	M-todo de prepara-Æo de antibiÄtico b-lactam
WO1998048037A1 (en) *	1997-04-22	1998-10-29	Dsm N.V.	A METHOD FOR CONTROLLING THE SOLUBILITY OF A β-LACTAM NUCLEUS
AU7648898A (en) *	1997-04-22	1998-11-13	Gist-Brocades B.V.	Process for the fermentative production of deacylated cephalosporins
SI0915988T1 (en) *	1997-04-22	2003-06-30	Dsm N.V.	Process for the fermentative production of deacylated cephalosporins
US6319684B1 (en)	1997-04-22	2001-11-20	Dms N.V.	Process for the fermentative production of cephalosporin
AU1772099A (en) *	1997-12-24	1999-07-19	Isis Innovation Limited	Modified deacetoxycephalosporin c synthase (daocs) and x-ray structure
ES2186347T3 (es) *	1998-03-27	2003-05-01	Dsm Nv	Nuevo procedimiento de produccion por fermentacion de cefalosporina.
US6383773B2 (en) *	1998-04-23	2002-05-07	Massachusetts Institute Of Technology	Penicillin conversion
PL344863A1 (en) *	1998-05-19	2001-11-19	Dsm Nv	Improved in vivo
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)
BRPI0110774B8 (pt)	2000-05-13	2021-05-25	Smithkline Beecham Plc	processo para purificação de um sal de ácido clavulânico
BRPI0621278A2 (pt)	2005-12-28	2011-12-06	Dsm Ip Assests Bv	acilases mutantes
ES2423454T3 (es) *	2006-02-23	2013-09-20	Dsm Sinochem Pharmaceuticals Netherlands B.V.	Producción mejorada de cefalosporina
EP2123772A1 (de)	2008-04-29	2009-11-25	DSM IP Assets B.V.	Beta-Lactamantibiotikum produzierende Stämme
CN102119213A (zh) *	2008-08-05	2011-07-06	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
CN102131921A (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
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
WO2010115838A1 (en)	2009-04-03	2010-10-14	Dsm Ip Assets B.V.	Fermentation process
HUE035540T2 (en)	2010-06-22	2018-05-02	Dsm Sinochem Pharm Nl Bv	Air bubble fermentation process
EP2614066B1 (de)	2010-09-07	2017-11-29	DSM Sinochem Pharmaceuticals Netherlands B.V.	Verfahren zur herstellung von cephalosporinen
EA023822B1 (ru)	2011-03-03	2016-07-29	Дсм Синокем Фармасьютикалз Нидерландз Б.В.	Разложение соединений пенициллина
WO2015091455A1 (en)	2013-12-17	2015-06-25	Dpx Holdings B.V.	Bioreactor
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

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DE3789880T2 (de) *	1986-01-31	1994-09-08	Beecham Group Plc	Isolierung und Expression von bei der Biosynthese von Beta-Laktamen beteiligten Genen.
HUT43644A (en) *	1986-11-17	1987-11-30	Univ Oxford	Process for producing 3-substituted-cephalosporines
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KR0171897B1 (ko) *	1989-12-27	1999-02-01	후지사와 도모끼찌로	7-아미노세펨 화합물 또는 그 염류의 제조 방법
SK280569B6 (sk) *	1991-10-15	2000-03-13	Gist-Brocades B.V.	Biologický spôsob výroby kyseliny7-aminodeacetylce

1992
- 1992-08-28 US US07/933,469 patent/US5318896A/en not_active Expired - Lifetime
- 1992-09-07 IL IL10307692A patent/IL103076A/en not_active IP Right Cessation
- 1992-09-07 NZ NZ244236A patent/NZ244236A/en not_active IP Right Cessation
- 1992-09-10 CA CA002077921A patent/CA2077921C/en not_active Expired - Fee Related
- 1992-09-10 MX MX9205175A patent/MX9205175A/es unknown
- 1992-09-10 CN CN92112278A patent/CN1066488C/zh not_active Expired - Lifetime
- 1992-09-11 DK DK92308286T patent/DK0532341T3/da active
- 1992-09-11 RU RU94017674/13A patent/RU2178808C2/ru not_active IP Right Cessation
- 1992-09-11 CZ CZ1994532A patent/CZ287357B6/cs not_active IP Right Cessation
- 1992-09-11 UA UA94005434A patent/UA41292C2/uk unknown
- 1992-09-11 RO RO94-00380A patent/RO115886B1/ro unknown
- 1992-09-11 KR KR1019940700777A patent/KR940702544A/ko active Granted
- 1992-09-11 ES ES92308286T patent/ES2126588T3/es not_active Expired - Lifetime
- 1992-09-11 EP EP97203374A patent/EP0843013A3/de not_active Withdrawn
- 1992-09-11 HU HU9400715A patent/HU217171B/hu not_active IP Right Cessation
- 1992-09-11 WO PCT/US1992/007711 patent/WO1993005158A1/en not_active Ceased
- 1992-09-11 AU AU23542/92A patent/AU657787B2/en not_active Ceased
- 1992-09-11 AT AT92308286T patent/ATE173017T1/de not_active IP Right Cessation
- 1992-09-11 DE DE69227494T patent/DE69227494T2/de not_active Expired - Fee Related
- 1992-09-11 KR KR1019940700777A patent/KR0132440B1/ko not_active Expired - Fee Related
- 1992-09-11 SK SK288-94A patent/SK282387B6/sk unknown
- 1992-09-11 JP JP5505516A patent/JP3027847B2/ja not_active Expired - Fee Related
- 1992-09-11 EP EP92308286A patent/EP0532341B1/de not_active Expired - Lifetime
- 1992-09-19 TW TW081107399A patent/TW270149B/zh active
1994
- 1994-03-09 BG BG98643A patent/BG62177B1/bg unknown
- 1994-03-10 NO NO19940848A patent/NO316742B1/no unknown
- 1994-03-10 FI FI941135A patent/FI108148B/fi active
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
CA2077921C (en)	1998-11-24
BG62177B1 (bg)	1999-04-30
JPH07501931A (ja)	1995-03-02
FI941135L (fi)	1994-03-10
NO940848L (no)	1994-03-10
JP3072101B2 (ja)	2000-07-31
ATE173017T1 (de)	1998-11-15
CA2077921A1 (en)	1993-03-12
DE69227494D1 (de)	1998-12-10
NZ244236A (en)	1994-03-25
KR0132440B1 (ko)	1998-04-14
HUT69801A (en)	1995-09-28
WO1993005158A1 (en)	1993-03-18
SK282387B6 (sk)	2002-01-07
MX9205175A (es)	1994-02-28
ES2126588T3 (es)	1999-04-01
EP0532341B1 (de)	1998-11-04
FI108148B (fi)	2001-11-30
BG98643A (bg)	1995-03-31
CN1332247A (zh)	2002-01-23
KR940702544A (ko)	1994-08-20
HU9400715D0 (en)	1994-06-28
NO316742B1 (no)	2004-04-26
DE69227494T2 (de)	1999-04-08
CZ287357B6 (cs)	2000-11-15
US5318896A (en)	1994-06-07
FI941135A0 (fi)	1994-03-10
EP0843013A2 (de)	1998-05-20
JP2000060582A (ja)	2000-02-29
AU657787B2 (en)	1995-03-23
IL103076A0 (en)	1993-02-21
NO940848D0 (no)	1994-03-10
CN1075336A (zh)	1993-08-18
HU217171B (hu)	1999-12-28
CN1066488C (zh)	2001-05-30
EP0532341A1 (de)	1993-03-17
DK0532341T3 (da)	1999-07-19
AU2354292A (en)	1993-03-18
RO115886B1 (ro)	2000-07-28
SK28894A3 (en)	1994-09-07
JP3027847B2 (ja)	2000-04-04
EP0843013A3 (de)	1998-06-17
UA41292C2 (uk)	2001-09-17
CZ53294A3 (en)	1994-08-17
TW270149B (de)	1996-02-11
RU2178808C2 (ru)	2002-01-27

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