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Catalytic mechanism of C-glycoside metabolizing enzymes from human intestinal bacteria

Research Project

Project/Area Number 18K14940
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 47050:Environmental and natural pharmaceutical resources-related
Research InstitutionKyushu University of Health and Welfare (2021-2022)
Suzuka University of Medical Science (2018-2020)

Principal Investigator

Nakamura Kenichi  九州保健福祉大学, 薬学部, 講師 (70512002)

Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsC-配糖体 / 腸内細菌 / 代謝酵素 / 生薬 / プエラリン / C-グリコシル化 / 代謝 / puerarin / タンパク質結晶化 / Gfo/Idh/MocA / 酸化還元酵素 / mangiferin / 結晶化
Outline of Final Research Achievements

The aim of this study was to identify a catalytic mechanism of C-glycoside metabolizing enzyme derived from intestinal bacteria. Previous studies revealed that the puerarin metabolic reaction is a two-step enzymatic reaction. In this study, we identified the enzyme DgpA, which metabolizes puerarin to 3"-oxo-puerarin, in the presence of 3-oxo-glucose. We also revealed the mechanism of the enzyme DgpB-DgpC complex that metabolize the intermediate (3"-oxo-puerarin) to daidzein and 1,5-anhydro-D-erythro- hex-1-en-3-ulose.

Academic Significance and Societal Importance of the Research Achievements

配糖体は高極性・高分子量のため経口摂取後に消化管から吸収されにくく、消化管下部で腸内細菌による種々の代謝を受ける。腸内細菌による配糖体の代謝は、漢方薬の薬効発現と密接に関わっていることが知られている。
葛根湯の構成生薬である「カッコン」には、イソフラボンC-配糖体のプエラリンが多量に含まれている。本研究で同定したプエラリンC-配糖体代謝酵素は新規酵素であり、また、カッコンに含まれる主要成分の代謝酵素であることから、本研究は葛根等の薬効発現機構を解明する一助になると考える。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (7 results)

All 2022 2020 2019 2018

All Journal Article (3 results) (of which Peer Reviewed: 2 results) Presentation (4 results)

  • [Journal Article] 腸内細菌酵素による生薬成分<i>C</i>-配糖体の代謝2022

    • Author(s)
      中村 賢一
    • Journal Title

      Farumashia

      Volume: 58 Issue: 6 Pages: 567-571

    • DOI

      10.14894/faruawpsj.58.6_567

    • ISSN
      0014-8601, 2189-7026
    • Related Report
      2022 Annual Research Report
  • [Journal Article] Deglycosylation of isoflavone C-glucoside puerarin by combination of two recombinant bacterial enzymes and 3-oxo-glucose.2020

    • Author(s)
      Nakamura K., Zhu S., Komatsu K., Hattori M., Iwashima M.
    • Journal Title

      Appl Environ Microbiol.

      Volume: 86 Issue: 14

    • DOI

      10.1128/aem.00607-20

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Expression and Characterization of the Human Intestinal Bacterial Enzyme Which Cleaves the <i>C</i>-Glycosidic Bond in 3″-Oxo-puerarin2019

    • Author(s)
      Nakamura K., Zhu S., Komatsu K., Hattori M., Iwashima M.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Issue: 3 Pages: 417-423

    • DOI

      10.1248/bpb.b18-00729

    • NAID

      130007607188

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2019-03-01
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] ヒト腸内細菌由来酵素による生薬成分C-配糖体の代謝2022

    • Author(s)
      中村賢一
    • Organizer
      第2回 宮崎県北サイエンスフォーラム
    • Related Report
      2022 Annual Research Report
  • [Presentation] ヒト腸内細菌による和漢薬成分の代謝研究~C-配糖体puerarinの代謝機構の解析~2020

    • Author(s)
      中村賢一
    • Organizer
      第37回和漢医薬学会 次世代を担う若手研究者の会シンポジウム
    • Related Report
      2020 Research-status Report
  • [Presentation] 腸内細菌由来酵素群によるC-配糖体puerarinの代謝機構の解析2019

    • Author(s)
      中村賢一、中根汐梨、Shu Zhu、小松かつ子、服部征雄、岩島誠
    • Organizer
      日本生薬学会第66回年会
    • Related Report
      2019 Research-status Report
  • [Presentation] ヒト腸内細菌が産生する mangiferin 代謝酵素の機能解析2018

    • Author(s)
      中村賢一 、日置紘太朗、伊達知世、葉山舜臣、Shu Zhu、小松かつ子、服部征雄、岩島誠
    • Organizer
      日本生薬学会第65回年会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2024-01-30  

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