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2002 Fiscal Year Final Research Report Summary

Studies on genetic manipulation of polyketide synthase gene in Streptomyces

Research Project

Project/Area Number 13680676
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  Kitasato University, Kitasto Institute for Life Sciences, Professor, 北里生命科学研究所, 教授 (90159632)

Project Period (FY) 2001 – 2002
KeywordsStreptomyces / polyketide / biosynthetic gene / genome analysis
Research Abstract

Species of the genus Streptomyces are of major pharmaceutical interest because they synthesize a variety of bioactive secondary metabolites. Especially, the diversity of polyketide compounds observed not only their structures but also their biological activities. Polyketide compounds are synthesized by large multifunctional polypeptide(s). The minimum synthase unit contains β-ketoacylsynthase (KS), acyltransferase (AT), and acyl carrier protein (ACP) to elongation β-keto carbon units. Some synthase unit consist of additional b-carbonyl processing domain(s) b-ketoredutase (KR), dehydratase (DH) or enoylreductase (ER). The composition of β-carbonyl processing domain(s) in each synthase unit reflects the structure of the polyketide backbone. Antiparasitic agent avermectin was produced by Streptomyces avermitilis that was discovered from Japan. We have already cloned entire gene cluster for avermectin biosynthesis with the size of about 85 kb. Within the 90 kb gene cluster for avermectin biosynthesis, the central 65 kb segment was encoded four large multifunctional polyketide synthases. Current recombinant technology is available to introduce a wide variety of specified genetic changes into multifunctional polyketide synthase genes. Avermectin polyketide synthase does not contain ER domain, therefore, fully reduced carbon chains are not found in the polyketide aglycon moiety. We introduced to integrate ER domain gene from other polyketide synthase gene at the module 2 of avermectin PKS aveA1 gene. Resultant recombinants produced small amount of dihydroavermectins. This result is useful for the modification of structure of natural products from Streptomyces strains to improve efficacy and reduction of toxicity.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] 池田 治生, 大村 智: "放線菌ポリケチド合成酵素遺伝子の解析とその応用"バイオサイエンスとインダストリー. 59. 26-29 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Omura, S., Ikeda, H.et al.: "Genome sequence of an industrial microorganism Streptomyces avermitilis : Deducing the ability of producing secondary metabolites"Proc. Natl. Acad. Sci. USA. 25. 12215-12220 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 池田 治生, 大村 智: "ポストゲノム時代を迎えての放線菌代謝産物研究"ファルマシア. 38. 829-833 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 池田 治生, 石川 淳, 大村 智: "放線菌の全ゲノム配列決定とその意義"蛋白質 核酸 酵素. 47. 1845-1850 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 池田 治生, 大村 智: "有用生物のゲノム研究の現状-4 放線菌"化学と生物. 49. 694-700 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ikeda, H.et al.: "Complete Genome Sequence and Comparative Analysis of the Industrial Microorganism Streptomyces avermitilis"Nat. Biotechnol. 21. 526-531 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Ikeda., and S.Omura.: "Analysis and application of polyketide synthase gene in Streptomyces"Bioscience and Bioindustry. 59. 26-29 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Omura., and H.Ikeda., et al.: "Genome sequence of an industrial microorganism Streptomyces avermitilis: Deducing the ability of producing secondary metabolites"Proc. Natl. Acad. Sci. USA. 25. 12215-12220 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Ikeda., and S.Omura.: "Studies on microbial products after the completion of genome sequence of Streptomyces"Pharmacia. 38. 829-833 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Ikeda., J.Ishikawa., and S.Omura.: "Genome analysis of Streptomyces"PNE. 47. 1845-1850 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Ikeda., and S.Omura.: "Current tops of industrial microorganism, Streptomyces"Kagaku To Seibutsu. 49. 694-700 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Ikeda., and J.Ishikawa., et al.: "Complete Genome Sequence and Comparative Analysis of the Industrial Microorganism Streptomyces avermitilis"Nat. Biotechnol. 21. 526-531 (2003)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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