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Genetic Engineering for Bio-active Natural Produtcs

Research Project

Project/Area Number 09044212
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Bioorganic chemistry
Research InstitutionToyama Medical & Pharmaceutical University

Principal Investigator

SANKAWA Ushio  Toyama Medical & Pharmaceutical University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (60012613)

Co-Investigator(Kenkyū-buntansha) SHIBUYA Masaaki  Graduate School of The University of Tokyo, Division of Pharmaceutical Sciences, Associate Professor, 大学院・薬学系研究科, 助教授 (50170923)
HAYASHI Toshimitsu  Toyama Medical & Pharmaceutical University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (40092796)
MACRE Bradle  ワシントン大学, 化学科, 研究助教授
FLOSS Heimg  ワシントン大学, 化学科, 教授
斎藤 直子 (岩浪 直子)  富山医科薬科大学, 薬学部, 助手 (90283077)
黒崎 文也  富山医科薬科大学, 薬学部, 講師 (70143865)
FLOSS Heinz  ワシントン大学, 化学科, 教授
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥10,300,000 (Direct Cost: ¥10,300,000)
Fiscal Year 1999: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1998: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1997: ¥3,500,000 (Direct Cost: ¥3,500,000)
Keywordschalcone synthase / diterpene / triterpene / antibiotic / polyketide / carotenoid / カルコン合成酵素(CHS) / スチルベン合成酵素(STS) / 放線菌 / シグナルペプチド / 非メバロン酸経路 / chalcone synthase / stilbene synthase / CHS superfamily / 交差反応 / メチロトフ酵母 / pNOTeI / Candida boidinii
Research Abstract

This study has been focussed on the biosynthesis of polyketide and terpenoids in the both countries. Plant plyketide synthases, chalcone and stilbene synthases were mainly investigated, in particular on their reaction mechanism in collaboration between Toyama Medical & Pharmaceutical University and the University of Tokyo. Heterologous expression system to produce a large amount of proteins were introduced from the University of Tokyo and the expressed proteins have been subjected in the trials of recrystallization. We have been investigated to obtain crystals with true substrates or reaction products. In the biosynthesis of isoprenoids, tetra- and bi-cyclic diterpenes of Scoparia dulcis have been shown to be biosynthesized via mevalonate independent pathway and geranylgeranyl diphophate synthase was cloned from this plant. It contained signal peptide targeting chloroplats supporting the diterpenes are biosynthesized in chloroplasts. cDNAs related to the biosynthesis of carotenoid were cloned from carrot and they also possess signal peptides. Characterization of the key reactions in tri-terpenoids biosynthesis was studied in the university of Tokyo. The group of USA mainly provide us technology transfer of gene cloning in particular polyketide biosynthesis enzymes. They contributeed one chapter in Comprehensive Natural Products Chemistry which was edited by the head investigator.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] 三川 潮、他: "Mevalonate-independent biosynthesis of biclclic and tetracyclic diterpenes of Scoparia culcis L."Tetrahedron Lett.. 40. 8239-8243 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 三川 潮、他: "Cross-reaction of chalcon and stilbene synthesethase over-expressed in E. coli"FEBS Letters. 460. 457-461 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 渋谷雅明、他: "Chimeric Triterpene Synthase, A Possible Model for Multifunctional Triterpene Synthase"J. Am. Chem. Soc.. 121. 1208-1216 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 渋谷雅明、他: "The Branches of Lupeol Synthase in the Molecular Evolution of Plant Oxidosqualene Cyclase"Eur. J. Biochem.. 266. 302-307 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H. G. Floss 他: "Mechanism of the 2-Deoxygenation in the Biosynthesis of the Dioxyhexose Moieties of the Antibiotics"J. Am. Chem. Soc.. 121. 2611-2612 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] B. S. Moore 他: "Direct Evidence that the Rifamycin Polyketide Synthase Assembles Polyketide Chain Processively"Proc. Natl. Acad. Sci. USA.. 96. 9051-9056 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 三川 潮編: "Comprehensive Natural Products Chemistry Vol.1"Elsevier. 895 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ushio Sankawa: "Mevalonate-independent biosynthesis of bicyclic and tetracyclic diterpenes of Scopalia dulcis L."Tetrahedron Letters. 40. 8239-8243 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ushio Sankawa: "Cross-reaction of chalcone and stilbene synthase overexpressed in Escherlichia coli."FEBS Letters. 460. 457-461 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Masaaki Shibuya: "Chimeric Triterpene Synthase. A Possible Model for Multifunctional Triterpenene Synthase"J. Am. Chem. Soc.. 121. 1208-1216 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Masaaki Shibuya: "Two Branches of the Lupeol Synthase Gene in the Molecular Evolution of Plant Oxidosqualene Cyclases"Eur. J. Biochem.. 266. 302-307 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H. G. Floss: "Mechanism of the 2-Deoxygenation Step in the Biosynthesis of the Deoxyhexose Moieties of the Antibiotics Granticin and Oleandomycin"J. Am. Chem. Soc.. 121. 2611-2612 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] B. S. Moore: "Direct Evidence that the Rifamycin Polyketide Syntahse Assembles Polyketide Chains Processively"Proc. Nat. Acad. Sci. USA. 96. 9051-9056 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] U. Sankwa: "Volume Editor, Comprehensive Natural Products Chemistry, Vol. Polyketides and Other Secondary Metabolites Including Fatty acids and Their Derivatives"Elsevier, Amsterdam. 1-895 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 三川潮他: "Mevalonate-independent biosynthesis of bicyclic and tetracyclic diterpenes of Scoparia duleis L."Tetrahedron Letters. 40. 8239-8243 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 三川潮他: "Cross-reaction of chalcone and stilbene synthases overexpressed in E. coli"FEBS Letters. 460. 457-461 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 渋谷雅明他: "Chimeric Triterpene Synthase, A Possible Model for Multifunctional Triterpene Synthase"J. Amer. Chem. Soc.. 121. 1208-1216 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 渋谷雅明他: "The Branches of Lupeol Synthase in the Molecular Evolution of Plant Oxidosqualene Cyclase"Eur. J. Biochem. 266. 302-307 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H. G. Floss 他: "Mechanism of the 2-Deoxygentamycin in the Biosynthesis of the Deoxyhexose Moieties of the Antibiotics"J. Amer. Chem. Soc.. 121. 2611-2612 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] B. Moore 他: "Direct Evidence that the Rifamycin Polyketide Synthase Assembles Polyketide Chain Processively"Proc. Natl. Acad. Sci. U.S.A.. 96. 9051-9056 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 三川潮編: "Comprehensive Natural Products Vol. 1"Elsevier. 895 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 三川 潮 他: "Purification of 2-Hydroxylsoflavamome Dehydiatase" Phytochemistry. 49. 497-505 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 三川 潮 他: "product Identification of Dolyketids Synthesis of wA Gene" Tefrahedron Letters. 39. 7733-7736 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 三川 潮 他: "Re-identification of Aspergillus nidlans wA Gene" Tetrahedrom Letters. 40. 91-94 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 渋谷雅明他: "β Amymm Synthase cloming of Oxidosgnalexe Cyclase" Eur.J.Biochem. 256. 238-244 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.G.Floss 他: "Granticim Biosgnthetic Gene Cluster of St,vlolacentibor" Clemistry and Biology. 120. 7749-7759 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] B.S.Moore 他: "Enginecred Biosynthesis of Narel polyketides" J.Amer.chem.Soc.120. 7749-7759 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 三川 潮 編: "Comprelcensive Natural Products Vo11" Elsevier Sciona, 895 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ushio Sankawa: "Molecular Cloning of Pea cDNA Encoding Cycloartenol Synthase" Biol.Pharm.Bull.20. 770-775 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ushio Sankawa: "Efficient Production of Biologically Active Diterpenoids" Phytochemistry. 46. 517-520 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ushio Sankawa: KODANSHA, 296 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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