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Biosynthesis of illegal drug metabolites using heterologous expression system of drug metabolizing enzymes in yeast

Research Project

Project/Area Number 15K21275
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Legal medicine
Medical pharmacy
Research InstitutionToyama Prefectural University

Principal Investigator

Nishikawa Miyu  富山県立大学, 工学部, 研究員 (90749805)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords指定薬物 / 薬物代謝酵素 / 遺伝子組換え酵母 / 薬物代謝 / 酵母発現系 / 代謝物生合成
Outline of Final Research Achievements

Recently, widespread illegal drugs become social issues. Authentic standard of these metabolite are needed for analysis because these drugs are converted to metabolite by drug metabolizing enzymes (DMEs). In general, it is difficult or sometimes impossible to prepare the metabolites. Purpose of the present study is to prepare the metabolites of illegal drugs using heterologous expression system of DMEs in yeast.
Two monoamine oxidase (MAO) isoforms and five flavin-containing monooxygenase (FMO) isoforms were newly constructed using budding yeast cell. It was impossible to evaluate the activity of MAO or FMO toward illegal drugs because suitable substrate was not commercially available by legal restriction. We next tried to prepare the multiple metabolites from MDMA or MDA using expression system of CYP, COMT and UGT, which was established in previously. However, it was impossible to prepare the metabolites because first metabolic reaction by CYP was not occurred.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (10 results)

All 2018 2017 2016

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Metabolism of Sesamin and Drug-Sesamin Interaction2018

    • Author(s)
      Sakaki T, Yasuda K, Nishikawa M, Ikushiro S
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 138 Issue: 3 Pages: 357-363

    • DOI

      10.1248/yakushi.17-00191-4

    • NAID

      130006410757

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2018-03-01
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Whole-cell-dependent biosynthesis of sulfo-conjugate using human sulfotransferase expressing budding yeast.2018

    • Author(s)
      Nishikawa M, Masuyama Y, Nunome M, Yasuda K, Sakaki T, Ikushiro S
    • Journal Title

      Appl Microbiol Biotechnol

      Volume: 102 Issue: 2 Pages: 723-732

    • DOI

      10.1007/s00253-017-8621-x

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biosynthesis of Drug Glucuronide Metabolites in the Budding Yeast Saccharomyces cerevisiae.2016

    • Author(s)
      S. Ikushiro, M. Nishikawa, Y. Masuyama, T. Shouji, M. Fujii, M. Hamada, N. Nakajima, M. Finel, K. Yasuda, M. Kamakura and T. Sakaki
    • Journal Title

      Mol Pharm.

      Volume: 13 Issue: 7 Pages: 2274-2282

    • DOI

      10.1021/acs.molpharmaceut.5b00954

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 出芽酵母を用いたカニクイザルUDP-グルクロン酸転移酵素(UGT1A)発現系の構築2017

    • Author(s)
      生城真一、高平李可、増山優香、西川美宇、安田佳織、宇野泰弘、村山典恵、山崎浩史、榊利之
    • Organizer
      日本薬物動態学会第32回年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 出芽酵母菌体を用いたヒトフラビン含有モノオキシゲナーゼ(FMO)反応解析系の構築2017

    • Author(s)
      増山優香、西川美宇、安田佳織、榊利之、生城真一
    • Organizer
      日本薬物動態学会第32回年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 薬用植物の有効成分であるペンタガロイルグルコースのグルクロン酸抱合代謝2016

    • Author(s)
      藤井美春、西川美宇、小池りりい、生城真一、榊利之
    • Organizer
      平成27年度内外環境応答代謝酵素研究会
    • Place of Presentation
      静岡
    • Year and Date
      2016-09-18
    • Related Report
      2016 Research-status Report
  • [Presentation] Whole cell-dependent synthesis of drug metabolites using genetically engineered yeast cells2016

    • Author(s)
      Miyu Nishikawa, Toshiyuki Sakaki, Shinichi Ikushiro
    • Organizer
      Toyama Basel joint symposium 2016
    • Place of Presentation
      Basel, Switzerland
    • Year and Date
      2016-08-25
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Whole cell-dependent synthesis of phase I and phase II metabolites using genetically engineered yeast2016

    • Author(s)
      Toshiyuki Sakaki, Miyu Nishikawa, Shinichi Ikushiro
    • Organizer
      13th International Symposium on Cytochrome P450 Biodiversity
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2016-07-25
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 異物代謝における種差同定を目指した異物代謝酵素発現酵母株の構築2016

    • Author(s)
      生城真一、西川美宇、榊利之
    • Organizer
      第42回日本毒性学会学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2016-06-30
    • Related Report
      2016 Research-status Report
  • [Presentation] Whole cell-dependent synthesis of phase II metabolites using genetically engineered yeast cells2016

    • Author(s)
      Miyu Nishikawa, Shinichi Ikushiro, Toshiyuki Sakaki
    • Organizer
      International Workshop on Conjugation 2016
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2016-06-21
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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