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Development of anti-malarial drugs targeting porphyrin biosynthesis

Research Project

Project/Area Number 25660088
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Bioorganic chemistry
Research InstitutionTokyo Institute of Technology

Principal Investigator

Wachi Masaaki  東京工業大学, 生命理工学研究科, 教授 (90192822)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsアラレマイシン / 抗マラリア薬 / ポルフィリン / 5-アミノレブリン酸 / ポルフォビリノーゲン合成酵素 / hemA / ALAS / hemB / マラリア / 阻害剤 / PBGS
Outline of Final Research Achievements

Nineteen derivatives were synthesized using alaremycin as a lead compound. Heterologous expression systems were constructed with an E. coli hemB disruptant and PBGS genes derived from various organisms including malaria parasite. It was shown that sensitivity to alaremycin as well as its derivatives differ among these PBGSs.
Two genes encoding ALA synthase homologs, hemA and ALAS, were found in the genome sequence of the alaremycin producer strain Streptomyces sp. A012304. It was shown that the hemA gene was responsible for ALA biosynthesis by complementation test of an E. coli ALA auxotrophic mutant. On the other hand, it was revealed that the ALAS gene was involved in the biosynthesis of alaremycin together with its downstream three genes.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (13 results)

All 2016 2015 2013

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Acknowledgement Compliant: 1 results,  Open Access: 1 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Degradation of benzotrifluoride via the dioxygenase pathway in Rhodococcous sp. 0652402015

    • Author(s)
      Kenichi Yano, Masaaki Wachi, Sakiko Tsuchida, Tomoya Kitazume, Noritaka Iwai
    • Journal Title

      Bioscience, biotechnology, and Biochemistry

      Volume: 79 Issue: 3 Pages: 496-504

    • DOI

      10.1080/09168451.2014.982502

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] High crude violacein production from glucose by Escherichia coli engineered with interactive control of tryptophan pathway and violacein biosynthetic pathway.2015

    • Author(s)
      Fang, M.Y., Zhang, C., Yang, S., Cui, J.Y., Jiang, P.X., Lou, K., Wachi, M., Xing, X.H.
    • Journal Title

      Microb. Cell Fact.

      Volume: 14 Issue: 1 Pages: 8-8

    • DOI

      10.1186/s12934-015-0192-x

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] <small>L</small>-Glutamate Secretion by the N-Terminal Domain of the <i>Corynebacterium glutamicum</i> NCgl1221 Mechanosensitive Channel2013

    • Author(s)
      Yamashita C., Hashimoto K., Kumagai K., Takada A., Kawasaki H. and Wachi M
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 77 Issue: 5 Pages: 1008-1013

    • DOI

      10.1271/bbb.120988

    • NAID

      10031177589

    • ISSN
      0916-8451, 1347-6947
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] A role of the transcriptional regulator LldR (NCgl2814) in glutamate metabolism under biotin-limited conditions in <i>Corynebacterium glutamicum</i>2013

    • Author(s)
      Supkulsutra T, Maeda T, Kumagai K, Wachi M.
    • Journal Title

      The Journal of General and Applied Microbiology

      Volume: 59 Issue: 3 Pages: 207-214

    • DOI

      10.2323/jgam.59.207

    • NAID

      130004802243

    • ISSN
      0022-1260, 1349-8037
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] A Secondary Structure in the 5' Untranslated Region of <i>adhE</i> mRNA Required for RNase G-Dependent Regulation2013

    • Author(s)
      Ito K, Hamasaki K, Kayamori A, Nguyen PA, Amagai K, Wachi M.
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 77 Issue: 12 Pages: 2473-2479

    • DOI

      10.1271/bbb.130618

    • NAID

      130003381972

    • ISSN
      0916-8451, 1347-6947
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 抗生物質アラレマイシンの生合成経路2016

    • Author(s)
      森ひかる、岩井伯隆、和地正明
    • Organizer
      日本農芸化学会2016年度大会
    • Place of Presentation
      札幌
    • Year and Date
      2016-03-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] アラレマイシン生産菌Streptomyces sp. A012304ノポルホビリノーゲン合成酵素の特性2016

    • Author(s)
      上田沙蘭、岩井伯隆、和地正明
    • Organizer
      日本農芸化学会2016年度大会
    • Place of Presentation
      札幌
    • Year and Date
      2016-03-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] Treasure hunting: Screening of antibiotics with a new target of action2015

    • Author(s)
      Wachi, M.
    • Organizer
      56th international symposium of the Korean Society of Life Science
    • Place of Presentation
      Changwon, Korea
    • Year and Date
      2015-08-27
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] アラレマイシン生産菌Streptomyces sp. A012304の2種類の5-アミノレブリン酸合成遺伝子の解析2015

    • Author(s)
      岩井伯隆、森ひかる、和地正明
    • Organizer
      日本農芸化学会2015年度大会
    • Place of Presentation
      岡山
    • Year and Date
      2015-03-26 – 2015-03-29
    • Related Report
      2014 Research-status Report
  • [Presentation] アラレマイシン生産菌の2つのALA生合成酵素ホモログの機能解析2015

    • Author(s)
      森ひかる、岩井伯隆、和地正明
    • Organizer
      第9回日本ゲノム微生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-06 – 2015-03-08
    • Related Report
      2014 Research-status Report
  • [Presentation] 大腸菌hemB欠損株を宿主としたPBGS異種発現によるアラレマイシン感受性の評価系の構築2013

    • Author(s)
      矢野寛明、岩井伯隆、和地正明
    • Organizer
      日本生物工学会
    • Place of Presentation
      広島
    • Related Report
      2013 Research-status Report
  • [Presentation] Role of NCgl1221 mechanosnstive channel in glutamate production by Corynebacterium glutamicum.2013

    • Author(s)
      Wachi M, Yamashita C.
    • Organizer
      Genetics of Industrial Microorganisms
    • Place of Presentation
      Cancum, Mexico
    • Related Report
      2013 Research-status Report
  • [Presentation] Screening for inhibitors of Hfq-mediated RNA metabolism.2013

    • Author(s)
      Takada A, Wachi M.
    • Organizer
      Genetics of Industrial Microorganisms
    • Place of Presentation
      Cancum, Mexico
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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