NO315330B1 - Isolert DNA-molekyl, hybridvektor omfattende denne, Aspergillusstamme defisient i et A. niger asparaginproteasegen, A. niger protease og entransformert vert samt fremgangsmater for a fremstille de ulike elementene - Google Patents

Isolert DNA-molekyl, hybridvektor omfattende denne, Aspergillusstamme defisient i et A. niger asparaginproteasegen, A. niger protease og entransformert vert samt fremgangsmater for a fremstille de ulike elementene Download PDF

Info

Publication number: NO315330B1
Authority: NO; Norway
Prior art keywords: aspergillus; gene; niger; dna; asparagine
Prior art date: 1993-11-03

Application number

NO19944181A

Other languages

English (en)

Norwegian (no)

Other versions

NO944181L (no

NO944181D0 (no

Inventor

Frank Buxton

Gabor Jarai

Jacob Visser

Original Assignee

Novartis Ag

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.)

1993-11-03

Filing date

1994-11-02

Publication date

2003-08-18

1994-11-02 Application filed by Novartis Ag filed Critical Novartis Ag

1994-11-02 Publication of NO944181D0 publication Critical patent/NO944181D0/no

1995-05-04 Publication of NO944181L publication Critical patent/NO944181L/no

2003-08-18 Publication of NO315330B1 publication Critical patent/NO315330B1/no

Links

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239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 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
OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
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LCJVIYPJPCBWKS-NXPQJCNCSA-N thymosin Chemical compound SC[C@@H](N)C(=O)N[C@H](CO)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CO)C(=O)N[C@H](CO)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@H]([C@H](C)O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@H](CCC(O)=O)C(O)=O LCJVIYPJPCBWKS-NXPQJCNCSA-N 0.000 description 1
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239000011573 trace mineral Substances 0.000 description 1
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230000002103 transcriptional effect Effects 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
235000019263 trisodium citrate Nutrition 0.000 description 1
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239000011701 zinc Substances 0.000 description 1
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229910000368 zinc sulfate Inorganic materials 0.000 description 1
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 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
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/58—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from fungi
- C12N9/62—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from fungi from Aspergillus
- 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
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/58—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from fungi

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

NO19944181A 1993-11-03 1994-11-02 Isolert DNA-molekyl, hybridvektor omfattende denne, Aspergillusstamme defisient i et A. niger asparaginproteasegen, A. niger protease og entransformert vert samt fremgangsmater for a fremstille de ulike elementene NO315330B1 (no)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
EP93810764		1993-11-03

Publications (3)

Publication Number	Publication Date
NO944181D0 NO944181D0 (no)	1994-11-02
NO944181L NO944181L (no)	1995-05-04
NO315330B1 true NO315330B1 (no)	2003-08-18

Family

ID=8215057

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19944181A NO315330B1 (no)	1993-11-03	1994-11-02	Isolert DNA-molekyl, hybridvektor omfattende denne, Aspergillusstamme defisient i et A. niger asparaginproteasegen, A. niger protease og entransformert vert samt fremgangsmater for a fremstille de ulike elementene

Country Status (18)

Country	Link
US (2)	US5674728A (de)
EP (1)	EP0655497B1 (de)
JP (1)	JP3727678B2 (de)
KR (1)	KR100378507B1 (de)
AT (1)	ATE235556T1 (de)
AU (1)	AU688379B2 (de)
CA (1)	CA2134863C (de)
CY (1)	CY2471B1 (de)
DE (1)	DE69432336T2 (de)
DK (1)	DK0655497T3 (de)
ES (1)	ES2196019T3 (de)
FI (1)	FI119060B (de)
HU (1)	HU220360B (de)
IL (2)	IL168245A (de)
NO (1)	NO315330B1 (de)
NZ (1)	NZ264839A (de)
PT (1)	PT655497E (de)
ZA (1)	ZA948619B (de)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU1092297A (en) *	1995-12-07	1997-06-27	Novo Nordisk A/S	Selective inactivation of enzyme activities
AU1092897A (en) *	1995-12-15	1997-07-14	Novo Nordisk A/S	A funguns wherein the area, pepc and/or pepe genes have been inactivated
JP2000511429A (ja) *	1996-06-05	2000-09-05	ギストブロカデスベスローテンフェンノートシャップ	真菌メタロプロテアーゼ遺伝子
ATE313620T1 (de) *	1996-09-19	2006-01-15	Novozymes As	Wirtszellen und methoden für die produktion von proteinen
AU2006202723B2 (en) *	2001-02-23	2008-06-26	Dsm Ip Assets B.V.	Novel genes encoding novel proteolytic enzymes
KR100880087B1 (ko) *	2001-02-23	2009-01-23	디에스엠 아이피 어셋츠 비.브이.	신규 단백질 분해효소를 암호화하는 신규 유전자
EP1377664A2 (de) *	2001-02-23	2004-01-07	DSM IP Assets B.V.	Gene, die für proteolytische enzyme von aspargilli kodieren
US20090253173A1 (en) *	2008-04-08	2009-10-08	Danisco Us Inc., Genencor Division	Filamentous fungi with inactivated protease genes for altered protein production
FI121712B (fi) *	2009-04-30	2011-03-15	Ab Enzymes Oy	Uusi sieniperäinen proteaasi ja sen käyttö
BR112014016587A2 (pt)	2012-01-05	2020-10-27	Novartis Ag	células fúngicas filamentosas deficientes de protease e métodos de uso das mesmas
DK2852610T3 (en)	2012-05-23	2018-09-03	Glykos Finland Oy	PRODUCTION OF FUCOSYLED GLYCOPROTEIN
WO2015004241A2 (en)	2013-07-10	2015-01-15	Novartis Ag	Multiple proteases deficient filamentous fungal cells and methods of use thereof
AU2015293949B2 (en)	2014-07-21	2019-07-25	Teknologian Tutkimuskeskus Vtt Oy	Production of glycoproteins with mammalian-like N-glycans in filamentous fungi
CN106222096B (zh) *	2016-08-18	2018-02-23	滨州学院	一株塔宾曲霉菌ct1及其在盐碱地解磷方面的应用
CN121022803B (zh) *	2025-10-29	2026-01-09	内蒙古科为博生物科技有限公司	一种耐热性提高的酸性蛋白酶突变体PepA4及其应用

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB8415186D0 (en) *	1984-06-14	1984-07-18	Ciba Geigy Ag	Polypeptides
US4885249A (en) *	1984-12-05	1989-12-05	Allelix, Inc.	Aspergillus niger transformation system
GB8521496D0 (en) *	1985-08-29	1985-10-02	Ciba Geigy Ag	Repressible yeast promoters
GB8702475D0 (en) *	1987-02-04	1987-03-11	Ciba Geigy Ag	Expression system
JPH02500082A (ja) *	1987-03-12	1990-01-18	ジェネックス・コーポレーション	遺伝子操作された生物による生物粘着物質前駆体タンパク質類似体の生産
US4871824A (en) *	1987-03-13	1989-10-03	Minnesota Mining And Manufacturing Company	Variably crosslinked polymeric supports
US5252726A (en) *	1987-09-04	1993-10-12	Novo Nordisk A/S	Promoters for use in aspergillus
CA1333777C (en) *	1988-07-01	1995-01-03	Randy M. Berka	Aspartic proteinase deficient filamentous fungi
DE68913846T3 (de) *	1988-07-28	2002-10-02	Novartis Ag, Basel	Expressionssystem.
EP0421919A3 (en) *	1989-09-02	1992-04-15	Ciba-Geigy Ag	Polygalacturonase encoding fungal expression system
ZA909987B (en) *	1990-01-29	1991-09-25	Ciba Geigy	Novel fungal expression system
AU661844B2 (en) *	1991-04-01	1995-08-10	Merck Sharp & Dohme Corp.	Genes which influence (pichia) proteolytic activity, and uses therefor
DK47493D0 (da) *	1993-04-27	1993-04-27	Novo Nordisk As	Fremgangsmaade til fremstilling af ost

1994
- 1994-10-24 US US08/328,314 patent/US5674728A/en not_active Expired - Lifetime
- 1994-10-25 PT PT94810616T patent/PT655497E/pt unknown
- 1994-10-25 DK DK94810616T patent/DK0655497T3/da active
- 1994-10-25 EP EP94810616A patent/EP0655497B1/de not_active Expired - Lifetime
- 1994-10-25 ES ES94810616T patent/ES2196019T3/es not_active Expired - Lifetime
- 1994-10-25 DE DE69432336T patent/DE69432336T2/de not_active Expired - Lifetime
- 1994-10-25 AT AT94810616T patent/ATE235556T1/de active
- 1994-10-27 AU AU77514/94A patent/AU688379B2/en not_active Expired
- 1994-10-31 JP JP26757094A patent/JP3727678B2/ja not_active Expired - Lifetime
- 1994-11-01 IL IL168245A patent/IL168245A/en not_active IP Right Cessation
- 1994-11-01 IL IL11148294A patent/IL111482A/xx not_active IP Right Cessation
- 1994-11-01 CA CA002134863A patent/CA2134863C/en not_active Expired - Lifetime
- 1994-11-01 HU HU9403136A patent/HU220360B/hu unknown
- 1994-11-01 NZ NZ264839A patent/NZ264839A/en not_active IP Right Cessation
- 1994-11-02 FI FI945163A patent/FI119060B/fi not_active IP Right Cessation
- 1994-11-02 KR KR1019940028594A patent/KR100378507B1/ko not_active Expired - Lifetime
- 1994-11-02 NO NO19944181A patent/NO315330B1/no not_active IP Right Cessation
- 1994-11-02 ZA ZA948619A patent/ZA948619B/xx unknown
1996
- 1996-10-08 US US08/731,045 patent/US5756338A/en not_active Expired - Lifetime
2004
- 2004-08-10 CY CY0400062A patent/CY2471B1/xx unknown

Also Published As

Publication number	Publication date
DE69432336D1 (de)	2003-04-30
KR950014309A (ko)	1995-06-15
EP0655497A3 (de)	1997-05-07
JPH07213286A (ja)	1995-08-15
NZ264839A (en)	1996-03-26
CA2134863A1 (en)	1995-05-04
DE69432336T2 (de)	2003-12-04
HU9403136D0 (en)	1994-12-28
ATE235556T1 (de)	2003-04-15
IL111482A0 (en)	1995-01-24
FI119060B (fi)	2008-07-15
ES2196019T3 (es)	2003-12-16
ZA948619B (en)	1995-06-27
DK0655497T3 (da)	2003-07-21
CA2134863C (en)	2008-12-30
US5756338A (en)	1998-05-26
FI945163L (fi)	1995-05-04
NO944181L (no)	1995-05-04
FI945163A0 (fi)	1994-11-02
EP0655497A2 (de)	1995-05-31
IL168245A (en)	2009-12-24
AU7751494A (en)	1995-05-18
AU688379B2 (en)	1998-03-12
HUT69954A (en)	1995-09-28
CY2471B1 (en)	2005-06-03
NO944181D0 (no)	1994-11-02
IL111482A (en)	2005-08-31
EP0655497B1 (de)	2003-03-26
US5674728A (en)	1997-10-07
KR100378507B1 (ko)	2003-09-19
PT655497E (pt)	2003-07-31
HU220360B (hu)	2001-12-28
JP3727678B2 (ja)	2005-12-14

Legal Events

Date	Code	Title	Description
2014-11-10	MK1K	Patent expired

Publication	Publication Date	Title
EP1266011B1 (de)	2010-05-26	Pilz transkriptionsaktivator zur verwendung in verfahren zur herstellung von polypeptiden
JP2013121361A (ja)	2013-06-20	菌類細胞中で遺伝子を発現させるためのプロモーター
CA2134863C (en)	2008-12-30	Aspergillus niger aspartic protease
EP0574347B1 (de)	2003-10-15	Neue Schimmel-Protease
US5688663A (en)	1997-11-18	Gene encoding carboxypeptidase of Aspergillus niger
DK175569B1 (da)	2004-12-13	Rekombinant DNA-molekyle, fremgangsmåde til fremstilling deraf, transformeret vært indeholdende det rekombinante DNA-molekyle, fremgangsmåde til fremstilling af den transformerede vært samt fremgangsmåde til fremstilling af et polypeptid
EP1078080A1 (de)	2001-02-28	Verfahren zum herstellen von genetisch veränderten filamentösen pilzzellen
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