WO1998054308A3 - Polyketides and their synthesis and use - Google Patents

Polyketides and their synthesis and use Download PDF

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Publication number
WO1998054308A3
WO1998054308A3 PCT/GB1998/001559 GB9801559W WO9854308A3 WO 1998054308 A3 WO1998054308 A3 WO 1998054308A3 GB 9801559 W GB9801559 W GB 9801559W WO 9854308 A3 WO9854308 A3 WO 9854308A3
Authority
WO
WIPO (PCT)
Prior art keywords
rapamycin
gene
produced
cluster
rapl
Prior art date
Application number
PCT/GB1998/001559
Other languages
French (fr)
Other versions
WO1998054308A2 (en
Inventor
Peter Francis Leadlay
James Staunton
Lake Ee Khaw
Original Assignee
Biotica Tech Ltd
Leadlay Peter F
James Staunton
Khaw Lake E
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 Biotica Tech Ltd, Leadlay Peter F, James Staunton, Khaw Lake E filed Critical Biotica Tech Ltd
Priority to DE69831943T priority Critical patent/DE69831943T2/en
Priority to AU76661/98A priority patent/AU7666198A/en
Priority to AT98924463T priority patent/ATE307198T1/en
Priority to EP98924463A priority patent/EP0983348B1/en
Publication of WO1998054308A2 publication Critical patent/WO1998054308A2/en
Publication of WO1998054308A3 publication Critical patent/WO1998054308A3/en
Priority to US10/307,595 priority patent/US7018808B2/en
Priority to US11/328,642 priority patent/US7381546B2/en
Priority to US12/129,295 priority patent/US20080287483A1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D498/18—Bridged systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
    • C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
    • C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
    • 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
    • C12N9/88—Lyases (4.)
    • 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
    • C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/18—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin
    • C12P17/182—Heterocyclic compounds containing nitrogen atoms as the only ring heteroatoms in the condensed system
    • 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
    • C12P19/00—Preparation of compounds containing saccharide radicals
    • C12P19/44—Preparation of O-glycosides, e.g. glucosides
    • C12P19/60—Preparation of O-glycosides, e.g. glucosides having an oxygen of the saccharide radical directly bound to a non-saccharide heterocyclic ring or a condensed ring system containing a non-saccharide heterocyclic ring, e.g. coumermycin, novobiocin
    • C12P19/62—Preparation of O-glycosides, e.g. glucosides having an oxygen of the saccharide radical directly bound to a non-saccharide heterocyclic ring or a condensed ring system containing a non-saccharide heterocyclic ring, e.g. coumermycin, novobiocin the hetero ring having eight or more ring members and only oxygen as ring hetero atoms, e.g. erythromycin, spiramycin, nystatin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide

Abstract

The rapamycin gene cluster is an example of a gene cluster which includes a gene (rapL) leading to the formation of a precursor compound (pipecolic acid, in this case) which is required for inclusion in the larger product (rapamycin) produced by the enzymes encoded by the cluster. We have produced a mutant strain containing a rapamycin gene cluster in which the rapL gene is disabled. The strain does not naturally produce rapamycin but does so if fed with pipecolic acid. By feeding with alternative carboxylic acids we have produced variants of rapamycins. Tests have shown biological activity.
PCT/GB1998/001559 1997-05-28 1998-05-28 Polyketides and their synthesis and use WO1998054308A2 (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
DE69831943T DE69831943T2 (en) 1997-05-28 1998-05-28 POLYETHYDES AND THEIR PREPARATION AND APPLICATION
AU76661/98A AU7666198A (en) 1997-05-28 1998-05-28 Polyketides and their synthesis and use
AT98924463T ATE307198T1 (en) 1997-05-28 1998-05-28 POLYKETIDES AND THEIR PRODUCTION AND USE
EP98924463A EP0983348B1 (en) 1997-05-28 1998-05-28 Polyketides and their synthesis and use
US10/307,595 US7018808B2 (en) 1997-05-28 2002-12-02 Polyketides and their synthesis and use
US11/328,642 US7381546B2 (en) 1997-05-28 2006-01-10 Polyketides and their synthesis and use
US12/129,295 US20080287483A1 (en) 1997-05-28 2008-05-29 Polyketides and Their Synthesis and Use

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB9710962.3A GB9710962D0 (en) 1997-05-28 1997-05-28 Polyketides and their synthesis
GB9710962.3 1997-05-28

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US09424751 A-371-Of-International 1998-05-28
US10/307,595 Continuation US7018808B2 (en) 1997-05-28 2002-12-02 Polyketides and their synthesis and use

Publications (2)

Publication Number Publication Date
WO1998054308A2 WO1998054308A2 (en) 1998-12-03
WO1998054308A3 true WO1998054308A3 (en) 1999-04-08

Family

ID=10813155

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1998/001559 WO1998054308A2 (en) 1997-05-28 1998-05-28 Polyketides and their synthesis and use

Country Status (8)

Country Link
US (3) US7018808B2 (en)
EP (1) EP0983348B1 (en)
AT (1) ATE307198T1 (en)
AU (1) AU7666198A (en)
DE (1) DE69831943T2 (en)
ES (1) ES2251084T3 (en)
GB (1) GB9710962D0 (en)
WO (1) WO1998054308A2 (en)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6495348B1 (en) 1993-10-07 2002-12-17 Regents Of The University Of Minnesota Mitomycin biosynthetic gene cluster
EP1153124A2 (en) 1999-02-09 2001-11-14 The Board Of Trustees Of The Leland Stanford Junior University Methods to mediate polyketide synthase module effectiveness
US7001748B2 (en) 1999-02-09 2006-02-21 The Board Of Trustees Of The Leland Stanford Junior University Methods of making polyketides using hybrid polyketide synthases
ES2283344T3 (en) 1999-10-29 2007-11-01 Kosan Biosciences, Inc. RAPAMYCIN ANALOGS.
FR2825717B1 (en) 2001-06-08 2005-02-18 Rhodia Chimie Sa STEREOSELECTIVE PREPARATION OF CYCLIC AMINO ACIDS
MXPA05000139A (en) 2002-07-16 2005-04-11 Biotica Tech Ltd Production of polyketides and other natural products.
US7585517B2 (en) * 2003-09-18 2009-09-08 Macusight, Inc. Transscleral delivery
WO2005100366A1 (en) 2004-04-14 2005-10-27 Wyeth Proline cci-779 (proline-rapamycin 42-ester with 2,2-bis (hydroxymethyl) propionic acid) and two-step enzymatic synthesis of proline cci-779 and cci-779 using microbial lipase
GB0417852D0 (en) * 2004-08-11 2004-09-15 Biotica Tech Ltd Production of polyketides and other natural products
SI1848431T1 (en) * 2005-02-09 2016-05-31 Santen Pharmaceutical Co., Ltd. Liquid formulations for treatment of diseases or conditions
US8663639B2 (en) * 2005-02-09 2014-03-04 Santen Pharmaceutical Co., Ltd. Formulations for treating ocular diseases and conditions
JP5528708B2 (en) 2006-02-09 2014-06-25 参天製薬株式会社 Stable formulations and methods for preparing and using them
US8222271B2 (en) * 2006-03-23 2012-07-17 Santen Pharmaceutical Co., Ltd. Formulations and methods for vascular permeability-related diseases or conditions
US20080265343A1 (en) * 2007-04-26 2008-10-30 International Business Machines Corporation Field effect transistor with inverted t shaped gate electrode and methods for fabrication thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0589703A1 (en) * 1992-09-24 1994-03-30 American Home Products Corporation Proline derivative of rapamycin, production and application thereof
WO1994010843A1 (en) * 1992-11-10 1994-05-26 Smithkline Beecham Corporation Rapamycin derivatives

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0589703A1 (en) * 1992-09-24 1994-03-30 American Home Products Corporation Proline derivative of rapamycin, production and application thereof
WO1994010843A1 (en) * 1992-11-10 1994-05-26 Smithkline Beecham Corporation Rapamycin derivatives

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
DENOYA CD ET AL: "A second branched-chain alpha-keto acid dehydrogenase gene cluster (bkdFGH) from Streptomyces avermitilis: its relationship to avermectin biosynthesis and the construction of a bkdF mutant suitable for the production of novel antiparasitic avermectins.", J BACTERIOL, JUN 1995, 177 (12) P3504-11, UNITED STATES, XP002079427 *
DUTTON CJ ET AL: "Novel avermectins produced by mutational biosynthesis.", J ANTIBIOT (TOKYO), MAR 1991, 44 (3) P357-65, JAPAN, XP002079430 *
HAFNER EW ET AL: "Branched-chain fatty acid requirement for avermectin production by a mutant of Streptomyces avermitilis lacking branched-chain 2-oxo acid dehydrogenase activity.", J ANTIBIOT (TOKYO), MAR 1991, 44 (3) P349-56, JAPAN, XP002079428 *
KHAW LE ET AL: "Mutational biosynthesis of novel rapamycins by a strain of Streptomyces hygroscopicus NRRL 5491 disrupted in rapL, encoding a putative lysine cyclodeaminase.", J BACTERIOL, FEB 1998, 180 (4) P809-14, UNITED STATES, XP002079433 *
LOMOVSKAYA, N. ET AL: "Gene disruption and replacement in the rapamycin-producing Streptomyces hygroscopicus strain ATCC 29253", MICROBIOLOGY,, vol. 143, March 1997 (1997-03-01), pages 875 - 883, XP002079431 *
MOLNAR I ET AL: "Organisation of the biosynthetic gene cluster for rapamycin in Streptomyces hygroscopicus: analysis of genes flanking the polyketide synthase", GENE, vol. 169, no. 1, 22 February 1996 (1996-02-22), pages 1-7, XP004042979 *
SCHWECKE T ET AL: "The biosynthetic gene cluster for the polyketide immunosuppressant rapamycin.", PROC NATL ACAD SCI U S A, AUG 15 1995, 92 (17) P7839-43, UNITED STATES, XP002079432 *
TANG L ET AL: "Amino acid catabolism and antibiotic synthesis: valine is a source of precursors for macrolide biosynthesis in Streptomyces ambofaciens and Streptomyces fradiae.", J BACTERIOL, OCT 1994, 176 (19) P6107-19, UNITED STATES, XP002079429 *

Also Published As

Publication number Publication date
US20030104585A1 (en) 2003-06-05
ATE307198T1 (en) 2005-11-15
DE69831943D1 (en) 2006-03-02
ES2251084T3 (en) 2006-04-16
EP0983348B1 (en) 2005-10-19
US7018808B2 (en) 2006-03-28
GB9710962D0 (en) 1997-07-23
US7381546B2 (en) 2008-06-03
AU7666198A (en) 1998-12-30
US20060105436A1 (en) 2006-05-18
WO1998054308A2 (en) 1998-12-03
DE69831943T2 (en) 2006-07-06
US20080287483A1 (en) 2008-11-20
EP0983348A2 (en) 2000-03-08

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