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Analysis of genes for polyketide symthases in avermectin-producing Streptomyces avermitilis.

Research Project

Project/Area Number 10680573
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Bioorganic chemistry
Research InstitutionKitasato University

Principal Investigator

IKEDA Haruo  School of Pharmaceutical Sciences, Kitasato University, Associate Professor, 薬学部, 助教授 (90159632)

Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywordspolyketide synthase / avermectin / biosynthetic genes / antibiotics / Streptomyces / ポリケチド化合物 / オンコセルカ症 / 駆虫薬
Research Abstract

Analysis of the gene cluster from Streptomyces avermitilis that governs the biosynthesis of the polyketide anthelmintic avermectin revealed that it contains four large open reading frames (ORFs) encoding giant multifunctional polypeptides of the avermectin polyketide synthase (AVES 1, AVES 2, AVES 3 and AVES 4). These clustered polyketide synthase genes responsible for avermectin biosynthesis together encode 12 homologous sets of enzyme activities (modules), each catalyzing a specific round of polyketide chain elongation. The clustered genes encoding polyketide synthase are organized as two sets of six modular repeats, aveAI and aveAII, which are convergently transcribed. The total of 55 constituent active sites makes this the most complex multifunctional enzyme system identified to date. The sequenced DNA region contains 14 additional open reading frames, some of which encode polypeptides governing other key steps in avermectin biosynthesis. Between the two sets of polyketide synthase genes lie two genes involved in post polyketide modification, one of which encodes cynthochrome P450 hydroxylase that probably catalyzes furan ring formation at C6 to C8a. Immediately right of the large polyketide synthase genes is a set of genes involved in oleandrose biosynthesis and its transglycosylation to polyketide-derived aglycons. This cluster includes eight genes but one is not functional in the biosynthesis of avermectin. On the left side of polyketide synthase genes, Two open reading frames encoding methyltransferase and non-polyketide synthase ketoreductase involved in post polyketide modification are located to the left of the polyketide synthase genes and an adjacent gene encodes a regulatory function which may be involved in activation of the transcription of avermectin biosynthetic genes.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] 池田治生: "コンビナトリアル・バイオシンセシス"蛋白質核酸酵素. 43・9. 1265-1277 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Haruo Ikeda: "Organization of the biosynthetic gene cluster for the polyketide authelmintic macrolide avermectin in Streptomyces avermitilis"Proc. Natl. Acad. Sci. U.S.A.. 96. 9509-9514 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Haruo Ikeda: "Genetic analysis of biosyntheis of polyketide anthelmintic macrolide avermectin in Streptomyces avermitilis."Actinomycetologica. 13・2. 94-112 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Haruo Ikeda: "Organization of the biosynthetic gene cluster for avermectin in Streptomyces avermitilis: Analysis of enzymatic domains in four polyketide synthases."J. Ind. Microb. Biotech.. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ikeda, H. and Omura, S.: "Combinatorial Biosynthesis"Protein Nucleic acid & Enzyme. 43. 1265-1277 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ikeda, H., Nonomiya, T., Usami, M., Ohta, T. and Omura, S: "Organization of the biosynthetic gene cluster for the polyketide anthelmintic macrolide avermectin in Streptomyces avermitilis."Proc. Natl. Acad. Sci. USA. 96. 9509-9514 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ikeda, H.: "Genetic analysis of Biosyntheis of polyketide anthelmintic macrolide avermectin in Streptomyces avermitilis"Actinomycetologica. 96. 9509-9514 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ikeda, H., Nonomiya, T. and Omura, S.: "Organization of the biosynthetic gene cluster for avermectin in Streptomyces avermitilis: Analysis of enzymatic domains in four polyketide synthases."J. Ind. Microb. Biotech.. in press..

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 池田 治生: "コンビナトリアル・バイオシンセシス"蛋白質核酸酵素. 43・9. 1265-1277 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] HARUO IKEDA: "Organization of the biosynthetic gene cluster for the polykeride anthelmintic macrolide avermectin in streptomyces avermitilis"Proc. Natl. Acad. Sci. U.S.A. 96. 9509-9514 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Haruo IKEDA: "Genetic analysis of biosynthesis of polyketide anthdmiutic macrolide avermectin in streptomyces avermitilis"Actinomycetologica. 13・2. 94-112 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Haruo IKEDA: "Organization of biosynthetic gene cluster for aoermectin instreptomyces aoermitilis, Analysis of enzymatic aomains in four polyketidesynthase"J. lnd. Microb. Biotech.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 池田治生・大村智: "コンビナトリアル・バイオシンセシス" 蛋白質・核酸・酵素. 43. 1265-1277 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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