FI106965B - Nya biologiska förfarande för framställning av 7-ACA och 7-ADAC - Google Patents
Nya biologiska förfarande för framställning av 7-ACA och 7-ADAC Download PDFInfo
- Publication number
- FI106965B FI106965B FI941730A FI941730A FI106965B FI 106965 B FI106965 B FI 106965B FI 941730 A FI941730 A FI 941730A FI 941730 A FI941730 A FI 941730A FI 106965 B FI106965 B FI 106965B
- Authority
- FI
- Finland
- Prior art keywords
- adipoyl
- dna
- gene
- expandase
- strain
- Prior art date
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- 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 title claims abstract description 38
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- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 claims abstract description 16
- 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 claims abstract description 11
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- BQIMPGFMMOZASS-CLZZGJSISA-N (6r,7r)-7-amino-3-(hydroxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1CC(CO)=C(C(O)=O)N2C(=O)[C@@H](N)[C@H]21 BQIMPGFMMOZASS-CLZZGJSISA-N 0.000 claims abstract description 8
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Claims (9)
1. Biologiskt förfarande för framställning av 7-aminodeacetylkefalosporansyra (7-ADAC), kanne-5 tecknat därav, att det omfattar följande steg: 1. man upprätthäller en Penicillium chrysogenum -stam som producerar isopenicillin N i ett odlingsmedium som förmär bistä vid dess tillväxt och i odlingsmediet tillsätter adipatnäring som omfattar nägon eller flera av 10 adipinsyra, dess salter eller estrar, vilka nämnda Peni-cillium chrysogenum-stam förmär assimilera och utnyttja för produktion av adipoyl-6-aminopenicillansyra (adipoyl-
2. Biologisktförfarande för framställning av 7-5 aminokefalosporansyra (7-ACA), kännetecknat därav, att det omfattar följande steg: 1. man upprätthäller en Penicillium chrysogenum-stam som producerar isopenicillin N i ett odlingsmedium som förmär bistä vid dess tillväxt och i odlingsmediet 10 tillsätter adipatnäring som omfattar nägon eller flera av adipinsyra, dess salter eller estrar, vilka nämnda Penicillium chrysogenum-stam förmär assimilera och utnyttja för produktion av adipoyl-6-aminopenicillansyra (adipoyl-
3. Biologisktförfarande enligt patentkrav 1 eller 15 2, kännetecknat därav, att adipatnäringen är dinatriumadipat.
4. Biologisktförfarande enligt patentkrav 1 eller 2, kännetecknat därav, att DNA:t som kodar för expandas-, hydroxylas- och eventuellt acetyltransfe- 20 rasaktiviteterna härletts ur Cephalosporium acremonium.
5 DNA och vilken är PC 200, ATCC 74186, eller PC 300, ATCC 74187, vilka transformerats med den rekombinanta DNA-ex-pressionsvektorplasmiden pPEN/CEPH-1 respektive pTS-8, varvid expressionsvektorplasmiden pPEN/CEPH-1 väsentligen bestär av DNA som härletts frän Cephalosporium acremonium 10 och som kodar för expandas- och hydroxylasaktivitet, pro-motorn i IPNS-genen i Penicillium chrysogenum och DNA i en fleomycingen som selektiv marker, och varvid expressionsvektorplasmiden pTS-8 väsentligen bestär av DNA som härletts frän Cephalosporium acremonium och som kodar för 15 expandas-, hydroxylas- och acetyltransferasaktivitet, pro- motorn i IPNS-genen i Penicillium chrysogenum och DNA i en fleomycingen som selektiv marker.
5. Biologisktförfarande enligt patentkrav 4, kännetecknat därav, att ett enda bifunk- I t t ·''< tionellt expandas/hydroxylasenzym används.
6. Biologisktförfarande enligt patentkrav 1 eller , 25 2, kännetecknat därav, att adipoylamidaset . härletts ur en Pseudomonas-art.
• · · **” 7. Rekombinanta DNA-expressionsvektorer, plamiderna • · · ’·* " (1) PEN/CEPH-1 och (2) pTS-8, vilka kan integreras i kro- mosom-DNA i en rekombinant Penicillium chrysogenum-stam ****· 3 0 och vilka väsentligen bestär av DNA som kodar för expan- • · « ’,..5 dasaktivitet, hydroxylasaktivitet och eventuellt acetyl- .·. : transferasaktivitet och härletts ur Cephalosporium acre- • · · monium, en promoter som innehäller IPNS-genen ur Penicillium chrysogenum som driver expression av nämnda DNA som « « V,: 35 kodar för expandas-, hydroxylas- och eventuellt acetyl- • · · • · • · • · · 92 106965 transferasaktivitet, och DNA ur en fleomycingen som selek-tiv marker.
6-APA), varvid nämnda adipoyl-6-APA bildas, 15 2) man utför följande enzymatiska omvandlingar ge- nom in situ-expression av motsvarande gen: a) adipoyl-6-APA ringexpanderas in situ för bil-dande av adipoyl-7-aminodeacetoxikefalosporansyra (adipo-yl-7-ADCA) medelst expandasenzym, varvid nämnda P. chryso-20 genum-stam transformerats med DNA som kodar för expan-dasenzymaktivitet, vilken förmär godtaga nämnda adipoyl-6-APA som substrat, varvid som ett resultat av expression av jV. nämnda DNA det adipoyl-6-APA, vilket producerats av nämnda < c stam, även ringexpanderas in situ för bildande av adipoyl-' 25 7-ADCA, . b) 3-metylsidokedjan i adipoyl-7-ADCA hydroxyleras ·»· in situ för bildande av adipoyl-7-aminodeacetylkefalospo- • » · *·* ransyra (adipoyl-7-ADAC) medelst hydroxylasenzym, varvid nämnda P. chrysogenum- stam trans f ormerats med DNA som ko- o 3. dar för hydroxylasenzymaktivitet, vilken förmär godtaga * ! nämnda adipoyl-7-ADCA som substrat, varvid som ett resul- ,·* ; tat av expression av nämnda DNA det adipoyl-7-ADCA som • · · producerats av nämnda stam, även hydroxyleras in situ för > « "* bildande av adipoyl-7-ADAC, f · * · « • « · • · • · t • · • t · i 91 106965 c) adipoyl-7-ADAC acyleras in situ för bildande av adipoyl-7-aminokefalosporansyra (adipoyl-7-ACA) medelst acetyltransferasenzym, varvid nämnda P. chrysogenum-stam transformerats med DNA som kodar for acetyltransterasen-5 zymaktivitet, vilken förmär godtaga nämnda adipoyl-7-ADAC som substrat, varvid som ett resultat av expression av nämnda DNA det adipoyl-7-ADAC, vilket producerats av nämnda stam även acyleras in situ för bildande av adipoyl-7-ACA, och 10 3) nämnda adipoyl - 7-ACA bringas i kontakt med ett adipoylamidas, varvid adipoylsidokedjan avlägsnas och 7-ACA-produkten bildas, och sedan isoleras den nämnda pro-dukten.
6-APA), varvid nämnda adipoyl-6-APA bildas, 2. man utför följande enzymatiska omvandlingar ge-15 nom in situ-expression av motsvarande gen: a) adipoyl - 6-APA ringexpanderas in situ för bil-dande av adipoyl-7-aminodeacetoxikefalosporansyra (adipo-yl-7-ADCA) medelst expandasenzym, varvid nämnda P. chryso-genuin-stam transformerats med DNA som kodar för expan-20 dasenzymaktivitet, vilken förmär godtaga nämnda adipoyl-6-APA som substrat, varvid som ett resultat av expression av nämnda DNA det adipoyl-6-APA, vilket producerats av nämnda • at stam, även ringexpanderas in situ för bildande av adipoyl-J«t' 7-ADCA, 25 b) 3-metylsidokedjan i adipoyl-7-ADCA hydroxyleras . in situ för bildande av adipoyl-7-aminodeacetylkefalospo- • · · ···· ransyra (adipoyl-7-ADAC) medelst hydroxylasenzym, varvid • · t *.1 nämnda P. chrysogenum-stam transformerats med DNA som ko dar för hydroxylasenzymaktivitet, vilken förmär godtaga **.2; 30 nämnda adipoyl-7-ADCA som substrat, varvid som ett resul-tat av expression av nämnda DNA det adipoyl-7-ADCA som « · · . producerats av nämnda stam, även hydroxyleras in situ för bildande av adipoyl-7-ADAC, > c l C c c e * « I < · • « « • · « · « · « · 2 • · · 106965 3. nämnda adipoyl-7-ADAC bringas i kontakt med adi-poylamidas, varvid adipoylsidokedjan avlägsnas och 7-ADAC-produkten bildas, och sedan isoleras den nämnda produkten.
8. Penicillium chrysogenum-värdcell, som innehäller en expressionsvektorplasmid integrerad i sitt kromosomala
9. Förfarande för odling av en rekombinant Penicillium chrysogenum-värdcell för att inducera expression av 20 enzymer som deltar i kefalosporinsyntes, varvid värdcellen odlas under förhällanden som lämpar sig för genexpression, t'"j ktd, a värdcellen innehäller, integrerad i sitt kromosoma- ( < < IV. la DNA, antingen a) den rekombinanta DNA-expressionsvektorplasmiden 25 pPEN/CEPH-1 som väsentligen bestär av DNA som härletts . frän Cephalosporium acremonium och som kodar för expandas- • · · och hydroxylasaktivitet, en promotor innehällande IPNS- • · · *·* ' genen i Penicillium chrysogenum och DNA i en fleomycingen som selektiv marker, eller *:*” 30 b) den rekombinanta DNA-expressionsvektorplasmiden pTS-8 som väsentligen bestär av DNA som härletts frän / . Cephalosporium acremonium och som kodar för expandas-, • t* hydroxylas- och acetyltransf erasaktivitet, en promotor **··’ innehällande IPNS-genen frän Penicillium chrysogenum och : : : 35 DNA i en fleomycingen som selektiv marker. • · « « · • · « « ·
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US77783391A | 1991-10-15 | 1991-10-15 | |
| US77783391 | 1991-10-15 | ||
| US95349292A | 1992-10-06 | 1992-10-06 | |
| US95349292 | 1992-10-06 | ||
| PCT/US1992/008585 WO1993008287A1 (en) | 1991-10-15 | 1992-10-08 | Novel bioprocesses for preparing 7-aca and 7-adac |
| US9208585 | 1992-10-08 |
Publications (3)
| Publication Number | Publication Date |
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| FI941730A0 FI941730A0 (sv) | 1994-04-14 |
| FI941730L FI941730L (sv) | 1994-04-14 |
| FI106965B true FI106965B (sv) | 2001-05-15 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI941730A FI106965B (sv) | 1991-10-15 | 1994-04-14 | Nya biologiska förfarande för framställning av 7-ACA och 7-ADAC |
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-
1992
- 1992-10-08 KR KR1019940701210A patent/KR100227711B1/ko not_active Expired - Fee Related
- 1992-10-08 HU HU9401073A patent/HU219370B/hu not_active IP Right Cessation
- 1992-10-08 UA UA94005496A patent/UA47385C2/uk unknown
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- 1992-10-08 WO PCT/US1992/008585 patent/WO1993008287A1/en not_active Ceased
- 1992-10-08 SK SK431-94A patent/SK280569B6/sk unknown
- 1992-10-08 RO RO94-00603A patent/RO116648B1/ro unknown
- 1992-10-13 NZ NZ244714A patent/NZ244714A/en not_active IP Right Cessation
- 1992-10-14 CN CN92113331A patent/CN1074484A/zh active Pending
- 1992-10-14 DE DE69232581T patent/DE69232581T2/de not_active Expired - Fee Related
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- 1992-10-14 DK DK97204046T patent/DK0856516T3/da active
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- 1992-10-14 DK DK92309351T patent/DK0540210T3/da active
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- 1992-10-14 EP EP92309351A patent/EP0540210B1/en not_active Expired - Lifetime
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- 1992-10-14 DE DE69227750T patent/DE69227750T2/de not_active Expired - Fee Related
- 1992-10-15 YU YU92592A patent/YU48930B/sh unknown
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- 1992-10-22 TW TW081108424A patent/TW272233B/zh not_active IP Right Cessation
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1994
- 1994-04-13 BG BG98714A patent/BG62261B1/bg unknown
- 1994-04-14 NO NO19941345A patent/NO315802B1/no unknown
- 1994-04-14 FI FI941730A patent/FI106965B/sv not_active IP Right Cessation
- 1994-05-27 US US08/250,310 patent/US5559005A/en not_active Expired - Fee Related
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1995
- 1995-05-11 US US08/439,404 patent/US5629171A/en not_active Expired - Fee Related
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1997
- 1997-04-17 US US08/839,327 patent/US6017726A/en not_active Expired - Fee Related
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1999
- 1999-02-10 GR GR990400429T patent/GR3029343T3/el unknown
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2002
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Owner name: GIST-BROCADES B.V. |
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| MA | Patent expired |