• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Production of novel biologically active molecules based on the functional analysis of glycosylation enzymes related to secondary metabolism

Research Project

Project/Area Number 17510184
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Living organism molecular science
Research InstitutionMusashino University

Principal Investigator

ICHINOSE Koji  Musashino University, Research Institute of Pharmaceutical Sciences, Professor (40282610)

Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,850,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥150,000)
Fiscal Year 2007: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordsantibiotic / biosynthesis / actinomycetes / enzyme / oxido-reduction / 糖
Research Abstract

This research deals with the functional analysis of the biosynthetic enzymes of C-glycosylated antibiotics produced by Streptomyces spp. The target compounds are a class of aromatic antibiotics known as benzoisochromanequinones (BIQs). Representative are medermycin and granaticin, both carry the unique deoxysugar components, which are of great pharmaceutical interest. The achievements in this project are as follows.
(1) The functional expression of the deoxysugar biosynthetic enzymes involved in medermycin biosynthesis.
The Med-17 and 18 enzymes, both related to the formation of nucleotide-sugar intermediates in angolosamine component in medermycin, are heterologously expressed in Escherichia coli, and the recombinant enzymes were functionally characterized. Med-17 and 18 were revealed to TDP-glucose synthase and TDP-glucose 4,6-dehydratase, respectively.
(2) The functional characterization of the reducing and oxidizing enzymes involved in the BIQ molecules.
Actinorhodin(ACT) produced by Streptomyces coelicolor A3(2) is an aromatic polyketide antibiotic. n the ACT biosynthesis, a stereospecific ketoreductase(RED1) was heterologously expressed in E. coli, and enzymatic studies on RED1 with synthetic analogues. The enzyme preferred to accept an free acid form as its substrate, strongly suggesting that RED1 recognizes a protein free keto acid as the first committed intermediate of later biosynthetic steps. Separately, a novel shunt product, actinoperylone, has been isolated front a deletion mutant of the actVA-5and 6 genes involved for ACT biosynthesis. Spectoroscopic analysis revealed its perylenquinone-type skeleton with the four chiral centers, obviously derived from the dimerization of an ACT intermediate. The structure of actinoperylone indicates the essential role of ActVA-ORF5 in the oxygen introduction at C-6.

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report

Research Products

(27 results)

All 2008 2007 2006 2005 Other

All Journal Article (8 results) (of which Peer Reviewed: 4 results) Presentation (17 results) Remarks (2 results)

  • [Journal Article] Actinoperylone,a novel perylenequinone-type shunt product,from a deletion mutant of the actVA-ORF5 and ORF6 genes fro actinorhodin biosynthesis in Streptomyces coelicolor A3(2)2008

    • Author(s)
      Takaaki Taguchi
    • Journal Title

      Tetrahedron Letters 49

      Pages: 1208-1211

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Actinoperylone, a novel perylenequinone-type shunt product, form a deletion mutant of the actVA-ORF5 and ORF6 genes for actinorhodin biosynthesis in Streptomyces coelicolor A3(2)2008

    • Author(s)
      Takaaki Taguchi., Susumu Okamoto, Takayuki Itoh, Yutaka Ebizuka, Kozo Ochi, Koji Ichinose
    • Journal Title

      Tetrahedron Lett. 49

      Pages: 1208-1211

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Actinoperylone,a novel perylenequinone-type shunt product,from a deletion mutant of the actVA-ORF5 and ORF6 gengs fro actinorhodin biosynthesis in Streptomyces coelicolor A3(2)2008

    • Author(s)
      Takaaki Taguchi
    • Journal Title

      Tetrahedron Letters 49

      Pages: 1208-1211

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Actinorhodin Biosynthesis:Structural Requirements for Post-PKS Tailoring Intermediates Revealed by Functional Analysis of ActVI-ORF1 Ruductase2007

    • Author(s)
      Takayuki Itoh
    • Journal Title

      Biochemistry 46

      Pages: 8181-8188

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Actinorhodin Biosynthesis : Structural Requirements for Post-PKS Tailoring Intermediates Revealed by Functional Analysis of ActVI-ORF1 Reductase.2007

    • Author(s)
      Takayuki Itoh, Takaaki Taguchi, Meriel R. Kimberley, Kevin I. Booker-Milburn, G. Richard Stephenson, Yutaka Ebizuka, Koji Ichinose
    • Journal Title

      Biochemistry 46

      Pages: 8181-8188

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Functional studies on a ketoreductase gene from Streptomyces sp.AM-7 161 to control the stereochemistry in medermycin biosynthesis2005

    • Author(s)
      Aiying Li
    • Journal Title

      Bioorganic & Medical Chemistry 13

      Pages: 6856-6863

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Functional studies on a ketoreductase gene from Streptomyces sp. AM-7161 to control the stereochemistry in medermycin biosynthesis2005

    • Author(s)
      Aiying Li, Takayuki Itoh, Takaaki Taguchi, Ting Xiang., Yutaka Ebizuka, Koji Ichinose
    • Journal Title

      Bioorg. Med. Chem. 13

      Pages: 6856-6863

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Functional Studies on a Ketoreductase Gene from Streptomyces sp.AM-7161 to Control the Stereochemistry in Medermycin Biosynthesis.2005

    • Author(s)
      Aiying Li, Takayuki Itoh, Takaaki Taguchi, Ting Xiang, Yutaka Ebizuka, Koji Ichinose
    • Journal Title

      Bioorganic & Medicinal Chemistry 13

      Pages: 6856-6863

    • Related Report
      2005 Annual Research Report
  • [Presentation] ベンゾイソクロマンキノン系抗生物質の生合成研究(28)-actVA-ORF5,6破壊体からの新規化合物の単離・構造解析-2008

    • Author(s)
      田口 貴章
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2008-03-26
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Biosynthetic studies on benzoisochromanequineone(BIQ) antibiotics(26) actVA-ORF5 disruptant-2008

    • Author(s)
      Takaaki Taguchi, Susumu Okamoto, Takayuki Itoh, Yutaka Ebizuka, Koji Ichinose
    • Organizer
      The 127th annual meeting of the pharma-ceutical Society of Japan
    • Place of Presentation
      Yokohama
    • Year and Date
      2008-03-26
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ベンゾイソクロマンキノン系抗生物質の生合成研究(28)-actVA-ORF5, 6破壊体からの新規化合物の単離・構造決定-2008

    • Author(s)
      田口 貴章
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2008-03-26
    • Related Report
      2007 Annual Research Report
  • [Presentation] ベンゾイソクロマンキノン系抗生物質の生合成研究(27)-actVA-ORF5,6破壊体からの新規化合物の単離・構造解析-2007

    • Author(s)
      田口 貴章
    • Organizer
      日本放線菌学会
    • Place of Presentation
      しまなみ記念館(尾道)
    • Year and Date
      2007-06-01
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Biosynthetic studies on benzoisochromanequineone(BIQ) antibiotics(26) -Isolation and structural analysis of a novel compound from actVA-ORF5 disruptant-2007

    • Author(s)
      Takaaki Taguchi, Susumu Okamoto, Takayuki Itoh, Tomoyo Masuda Yutaka Ebizuka, Koji Ichinose
    • Organizer
      The annual meeting of the society for actinomycetes Japan
    • Place of Presentation
      Onomichi
    • Year and Date
      2007-06-01
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 放線菌抗生物質生合成に関わる構造修飾酵素の基質認識2007

    • Author(s)
      市瀬 浩志
    • Organizer
      日本薬学会第127年会 シンポジウム36"生合成機構の解明から有用物質生産系の構築へ"
    • Place of Presentation
      富山県民会館(富山)
    • Year and Date
      2007-03-30
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Substrate recognition of modification enzymes involved in the biosynthesis of actinomycetes antibiotics2007

    • Author(s)
      Koji Ichinose
    • Organizer
      The 127th annual meeting of the pharma-ceutical Society of Japan(Sympsium 36)
    • Place of Presentation
      Toyama
    • Year and Date
      2007-03-30
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Chemical tools to probe the enantioselectivity of RED1/RED2 reductions in polyketide tailoring steps2006

    • Author(s)
      G. Richard Stephenson
    • Organizer
      Chemical Biology:Directing Biosynthesis
    • Place of Presentation
      ケンブリッジ大学(英国)
    • Year and Date
      2006-09-11
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Chemical tools to probe the enantioselectivity of RED1/RED2 reductions in polyketide tailoring steps2006

    • Author(s)
      G Richard Stephenson, Emma Brennand, Cole Clissold, Kevin I, Booker-Milburn, Koji Ichinose
    • Organizer
      Chemical Biology : Directing Biosynthesis(The Royal Society of Chemistry)
    • Place of Presentation
      Cambridge, UK
    • Year and Date
      2006-09-11
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Purification and enzymatic analysis of stereospecific ketoreductase(RED1) involved in acthlorhodin biosyntheis2006

    • Author(s)
      Takayuki Itoh
    • Organizer
      International Conference on Biodiversity and Natural Products (ICOB-5 & ISCNP-25)
    • Place of Presentation
      京都(国立京都国際会館)
    • Year and Date
      2006-07-25
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Purification and enzymatic analysis of stereospecific ketoreductase(RED1) involved in actinorhodin biosynthesis2006

    • Author(s)
      Takayuki Itoh, Takaaki Taguchi, Yutaka Ebizuka, Koji Ichinose
    • Organizer
      International Conference on Biodiversity and Natural Products(ICOB-5 & ISCNP-25)
    • Place of Presentation
      Kyoto
    • Year and Date
      2006-07-25
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Functional analysis of a stereospecific ketoreductase involved in actinorhodin biosynthesis2006

    • Author(s)
      Koji Ichinose
    • Organizer
      10th International Symposium on the Gnetics of Industrial Microorganisms(GIM2006)
    • Place of Presentation
      プラハ国際会議場(チェコ)
    • Year and Date
      2006-06-28
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Functional analysis of a stereospecific ketoreductase involved in actinorhodin biosynthesis2006

    • Author(s)
      Koji Ichinose, Takayuki Itoh, Takaaki Taguchi, Yutaka Ebizuka
    • Organizer
      10th International Symposium on the Gnetics of Industrial Microorganisms(GIM2006)
    • Place of Presentation
      Praque, Czeck
    • Year and Date
      2006-06-28
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ベンゾイソクロマンキノン(BIQ)抗生物質の生合成研究(26)-actVI-ORF1遺伝子産物RED1の精製と酵素学的解析-2006

    • Author(s)
      伊藤 崇敬
    • Organizer
      日本薬学会第126年会
    • Place of Presentation
      仙台(せんだいメディアテーク)
    • Year and Date
      2006-03-29
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Biosynthetic studies on benzoisochromanequineone(BIQ) antibiotics(26) -Purification and enzymatic analysis of act VI-ORFI gene product, RED1-2006

    • Author(s)
      Takayuki Itot, Takaaki Taguchi, Yutaka Ebizuka, Koji Ichinose
    • Organizer
      The 126th annual meeting of the pharma-ceutical society of Japan
    • Place of Presentation
      Sendai
    • Year and Date
      2006-03-29
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 天然デオキシ糖類の生合成(4)-メダマイシンのデオキシアミノ糖生合成遺伝子の機能解析-2006

    • Author(s)
      橋元 誠
    • Organizer
      日本農芸化学会
    • Place of Presentation
      京都(京都女子大学)
    • Year and Date
      2006-03-27
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Biosynthetic studies on deoxysugar(4) -Functional analysis of deoxyaminosugar biosynthetic genes involved in medermycin biosynthesis2006

    • Author(s)
      Makoto Hashimoto, takaaki Taguchi, Koji Ichinose
    • Organizer
      The annual meeting of the Japan Society for Bioscience, Biotechnology, and Agrocchemistry
    • Place of Presentation
      Kyoto
    • Year and Date
      2006-03-27
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.musashino-u.ac.jp/yakugaku/shoyakukagaku/

    • Related Report
      2007 Final Research Report Summary
  • [Remarks]

    • URL

      http://www.musashino-u.ac.jp/yakugaku/shoyakukagaku/

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2005-03-31   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi