WO2000077220A3 - Verfahren zur veränderung von peptidsynthetasen in der weise, dass sie ihre substrataminosäuren n-methylieren können - Google Patents

Verfahren zur veränderung von peptidsynthetasen in der weise, dass sie ihre substrataminosäuren n-methylieren können Download PDF

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Publication number
WO2000077220A3
WO2000077220A3 PCT/DE2000/001950 DE0001950W WO0077220A3 WO 2000077220 A3 WO2000077220 A3 WO 2000077220A3 DE 0001950 W DE0001950 W DE 0001950W WO 0077220 A3 WO0077220 A3 WO 0077220A3
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WO
WIPO (PCT)
Prior art keywords
amino acids
substrate amino
methylate
pps
activation domains
Prior art date
Application number
PCT/DE2000/001950
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English (en)
French (fr)
Other versions
WO2000077220A2 (de
Inventor
Ullrich Keller
Florian Schauwecker
Original Assignee
Ullrich Keller
Florian Schauwecker
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.)
Filing date
Publication date
Application filed by Ullrich Keller, Florian Schauwecker filed Critical Ullrich Keller
Priority to EP00945641A priority Critical patent/EP1190066A2/de
Priority to DE10081623T priority patent/DE10081623D2/de
Priority to AU59651/00A priority patent/AU5965100A/en
Priority to CA002418798A priority patent/CA2418798A1/en
Publication of WO2000077220A2 publication Critical patent/WO2000077220A2/de
Publication of WO2000077220A3 publication Critical patent/WO2000077220A3/de

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    • 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
    • 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
    • C12N9/10—Transferases (2.)
    • C12N9/1003—Transferases (2.) transferring one-carbon groups (2.1)
    • C12N9/1007—Methyltransferases (general) (2.1.1.)

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  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

Die Erfindung betrifft die Veränderung von Peptidsynthetasen (PPS) in der Weise, daß sie ihre Substrataminosäuren N-methylieren können. PPS sind Enzyme, die Peptide auf nicht-ribosomale Weise synthetisieren. Die PPS sind modular aufgebaut. Jedes Modul besitzt eine Aktivierungsdomäne, welche die jeweilige Substrataminosäure erkennt und kovalent bindet. Die von der PPS katalysierte Peptidsynthese erfolgt dann durch die Kondensation der kovalent gebundenen Substrataminosäuren. Eine geringe Anzahl der bekannten Aktivierungsdomänen ist in der Lage, die gebundenen Substrataminosäuren auch zu N-methylieren. Die hier beschriebene Erfindung ermöglicht die Umwandlung von Aktivierungsdomänen ohne N-Methyltransferase-Aktivität in Aktivienngsolomänen nu7 N-île-thyltransferase-Aktivität, wobei die ursprüngliche Substratspezifität erhalten bleibt.
PCT/DE2000/001950 1999-06-16 2000-06-15 Verfahren zur veränderung von peptidsynthetasen in der weise, dass sie ihre substrataminosäuren n-methylieren können WO2000077220A2 (de)

Priority Applications (4)

Application Number Priority Date Filing Date Title
EP00945641A EP1190066A2 (de) 1999-06-16 2000-06-15 Verfahren zur veränderung von peptidsynthetasen in der weise, dass sie ihre substrataminosäuren n-methylieren können
DE10081623T DE10081623D2 (de) 1999-06-16 2000-06-15 Verfahren zur Veränderung von Peptidsynthetasen in der Weise, daß sie ihre Substrataminosören N-methylieren können
AU59651/00A AU5965100A (en) 1999-06-16 2000-06-15 Method of modifying peptide synthetases such that they can n-methylate their substrate amino acids
CA002418798A CA2418798A1 (en) 1999-06-16 2000-06-15 Method of modifying peptide synthetases such that they can n-methylate their substrate amino acids

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19928313.3 1999-06-16
DE1999128313 DE19928313A1 (de) 1999-06-16 1999-06-16 Verfahren zur Veränderung von Peptidsynthefasen in der Weise, daß sie ihre Substrataminosäuren N-methylieren können

Publications (2)

Publication Number Publication Date
WO2000077220A2 WO2000077220A2 (de) 2000-12-21
WO2000077220A3 true WO2000077220A3 (de) 2001-03-29

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PCT/DE2000/001950 WO2000077220A2 (de) 1999-06-16 2000-06-15 Verfahren zur veränderung von peptidsynthetasen in der weise, dass sie ihre substrataminosäuren n-methylieren können

Country Status (5)

Country Link
EP (1) EP1190066A2 (de)
AU (1) AU5965100A (de)
CA (2) CA2418798A1 (de)
DE (2) DE19928313A1 (de)
WO (1) WO2000077220A2 (de)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11180738B2 (en) 2016-04-07 2021-11-23 Eth Zurich Method for producing an n-methylated (poly) peptide

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0578616A2 (de) * 1992-07-09 1994-01-12 Sandoz Ltd. Zyclosporine Synthetase
EP0637630A2 (de) * 1993-07-13 1995-02-08 ENIRICERCHE S.p.A. Verfahren zur biologischen Herstellung von Peptiden
EP0789078A2 (de) * 1995-08-09 1997-08-13 ENIRICERCHE S.p.A. Modifizierte Peptidsynthetasen, und deren Verwendung in die nicht-ribosomaler Herstellung von Peptiden
WO1999002659A2 (en) * 1997-07-09 1999-01-21 Biochemie Gesellschaft M.B.H. Method of altering the domains of cyclosporin synthetase to give a modified cyclosporin synthetase

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0578616A2 (de) * 1992-07-09 1994-01-12 Sandoz Ltd. Zyclosporine Synthetase
EP0637630A2 (de) * 1993-07-13 1995-02-08 ENIRICERCHE S.p.A. Verfahren zur biologischen Herstellung von Peptiden
EP0789078A2 (de) * 1995-08-09 1997-08-13 ENIRICERCHE S.p.A. Modifizierte Peptidsynthetasen, und deren Verwendung in die nicht-ribosomaler Herstellung von Peptiden
WO1999002659A2 (en) * 1997-07-09 1999-01-21 Biochemie Gesellschaft M.B.H. Method of altering the domains of cyclosporin synthetase to give a modified cyclosporin synthetase

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
BILLICH A ET AL.: "Formation of N-methylated peptide bonds in peptides and peptidols", BIOCHEM. PEPT. ANTIBIOT. (EDITOR(S): KLEINKAUF H; VON DOEHREN H.) PUBL: DE GRUYTER, BERLIN, FED. REP. GER., 1990, pages 57 - 59, XP000965466 *
BURMESTER J ET AL: "Highly conserved N- methyltransferases as an integral part of peptide synthetases.", BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL, vol. 37, no. 2, October 1995 (1995-10-01), pages 201 - 207, XP000965322 *
KELLER U: "Actinomycin synthetases. Multifunctional enzymes responsible for the synthesis of the peptide chains of actinomycin.", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 262, no. 12, 25 April 1987 (1987-04-25), pages 5852 - 5856, XP002153253 *
MARAHIEL M A ET AL: "Modular peptide synthetases involved in nonribosomal peptide synthesis", CHEMICAL REVIEWS, vol. 97, no. 7, November 1997 (1997-11-01), pages 2651 - 2673, XP002133489 *
SCHAUWECKER F ET AL.: "Construction and in vitro analysis of a new bi-modular polypeptide synthetase for synthesis of N-methylated acyl peptides", CHEMISTRY AND BIOLOGY, vol. 7, no. 4, 20 March 2000 (2000-03-20), pages 287 - 297, XP000957461 *
SCHAUWECKER F ET AL.: "Molecular cloning of the actinomycin synthetase gene cluster from Streptomyces chrysomallus and functional heterologous expression of the gene encoding actinomycin synthetase II", JOURNAL OF BACTERIOLOGY, vol. 180, no. 9, May 1998 (1998-05-01), pages 2468 - 2474, XP002153252 *
SCHNEIDER A ET AL: "Targeted alteration of the substrate specificity of peptide synthetases by rational module swapping", MOLECULAR AND GENERAL GENETICS, vol. 257, no. 3, February 1998 (1998-02-01), pages 308 - 318, XP002141778 *

Also Published As

Publication number Publication date
WO2000077220A2 (de) 2000-12-21
CA2418798A1 (en) 2002-11-05
DE19928313A1 (de) 2000-12-21
EP1190066A2 (de) 2002-03-27
DE10081623D2 (de) 2002-05-29
CA2377592A1 (en) 2000-12-21
AU5965100A (en) 2001-01-02

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