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2012 Fiscal Year Final Research Report

Discovery of a biosynthetic gene cluster for an anti-tubercular agent its application for the establishment of overproduction system for the anti-tubercular agent and the production of anti-cancer drug-

Research Project

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Project/Area Number 22790068
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionHiroshima University

Principal Investigator

KUMAGAI Takanori  広島大学, 大学院・医歯薬保健学研究院, 准教授 (70274058)

Project Period (FY) 2010 – 2012
Keywords抗結核薬 / D-サイクロセリン / 生合成 / 異種発現 / 放線菌
Research Abstract

In the present study, the biosynthetic pathway for the anti -tubercular agent, D-cycloserine (DCS), was elucidated by the gene disruption analysis of the DCS biosynthetic gene cluster in a DCS-producing Streptomyces lavendulae ATCC11924. In addition, DCS production system in Escherichia (E.) coli was established by introducing the DCS biosynthetic genes into E. coli. Furthermore, DcsA was found to be a novel heme protein involved in the biosynthesis of DCS.

  • Research Products

    (12 results)

All 2013 2012 2011 2010

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

  • [Journal Article] Establishment of an in vitroD-cycloserine-synthesizing system by using O-ureido-L-serine synthase and D-cycloserine synthetase found in the biosynthetic pathway2013

    • Author(s)
      Uda, N., Matoba, Y., Kumagai, T., Oda, K., Noda, M., and Sugiyama, M
    • Journal Title

      Antimicrob. Agents Chemother

      Pages: in press

    • DOI

      DOI:10.1128/AAC.02291-12

    • Peer Reviewed
  • [Journal Article] Crystallographic study to determine the substrate specificity on an L-serine-acetylating enzyme found in the D-cycloserine biosynthetic pathway2013

    • Author(s)
      Oda, K., Matoba, Y., Kumagai, T., Noda, M., and Sugiyama, M
    • Journal Title

      J. Bacteriol

      Volume: 195 Pages: 1741-1749

    • DOI

      DOI:10.1128/JB.02085-12

    • Peer Reviewed
  • [Journal Article] Heme protein and hydroxyarginase necessary for biosynthesis of D-cycloserine2012

    • Author(s)
      Kumagai, T., Takagi, K., Koyama, Y., Matoba, Y., Oda, K., Noda, M., and Sugiyama, M
    • Journal Title

      Antimicrob. Agents Chemother

      Volume: 56 Pages: 3682-3689

    • DOI

      DOI:10.1128/AAC.00614-12

    • Peer Reviewed
  • [Journal Article] Molecular cloning and heterologous expression of a biosynthetic gene cluster for the antitubercular agent D-cycloserine produced by Streptomyces lavendulae. Antimicrob2010

    • Author(s)
      Kumagai, T., Koyama, Y., Oda, K., Noda, M., Matoba, Y., and Sugiyama, M
    • Journal Title

      Agents Chemother

      Volume: 54 Pages: 1132-1139

    • DOI

      DOI:10.1128/AAC.01226-09

    • Peer Reviewed
  • [Presentation] 抗結核薬 D-サイクロセリンの生合成に関与する DcsA タンパク質の機能解析2012

    • Author(s)
      熊谷孝則, 高木紀抄, 的場康幸, 野田正文, 杉山政則
    • Organizer
      2012 年度日本放線菌学会大会
    • Place of Presentation
      東京
    • Year and Date
      20120906-07
  • [Presentation] D-サイクロセリン生合成に関わるL-セリン-O-アセチルトランスフェラーゼの基質特異性に関する構造生物学的研究2012

    • Author(s)
      小田康祐, 的場康幸, 熊谷孝則, 野田正文, 杉山政則
    • Organizer
      2012 年度日本放線菌学会大会
    • Place of Presentation
      東京
    • Year and Date
      20120906-07
  • [Presentation] D-サイクロセリン生合成に関わるO-ウレイドL-セリン合成酵素の基質特異性に関する構造生物学的研究2012

    • Author(s)
      宇田成利, 的場康幸, 小田康祐, 野田正文, 熊谷孝則, 杉山政則
    • Organizer
      2012 年度日本放線菌学会大会
    • Place of Presentation
      東京
    • Year and Date
      20120906-07
  • [Presentation] A hydroxylation reaction necessary in the biosynthesis of an antitubercular antibiotic D-cycloserine2011

    • Author(s)
      Kumagai, T., Takagi, K., Noda, M., Oda, K., Matoba, Y., and Sugiyama, M
    • Organizer
      IUMS2011
    • Place of Presentation
      Sapporo, Japan
    • Year and Date
      20110906-10
  • [Presentation] 生合成酵素を用いたD-サイクロセリンの試験管内合成2011

    • Author(s)
      宇田成利,的場康幸,小田康祐,野田正文,熊谷孝則,杉山政則
    • Organizer
      第52回日本生化学会中国・四国支部例会
    • Place of Presentation
      広島
    • Year and Date
      20110513-14
  • [Presentation] D-サイクロセリン生合成遺伝子クラスターのクローニングとその機能解析2011

    • Author(s)
      高木紀抄, 熊谷孝則,小山佑介,宇田成利,小田康祐,野田正文,的場康幸,杉山政則
    • Organizer
      第52回日本生化学会中国・四国支部例会
    • Place of Presentation
      広島
    • Year and Date
      20110513-14
  • [Presentation] 遺伝子破壊を用いたD-サイクロセリン生合成遺伝子クラスターの機能解析2010

    • Author(s)
      熊谷孝則,小山祐介,小田康祐,野田正文,的場康幸,杉山政則
    • Organizer
      2010 年度日本放線菌学会大会
    • Place of Presentation
      東京
    • Year and Date
      20100902-03
  • [Presentation] D-サイクロセリン生合成に関与する酵素群の機能解析2010

    • Author(s)
      宇田成利,的場康幸,小田康祐,野田正文,熊谷孝則,杉山政則
    • Organizer
      2010 年度日本放線菌学会大会
    • Place of Presentation
      東京
    • Year and Date
      20100902-03

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Published: 2014-08-29   Modified: 2015-10-15  

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