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Frontiers in metabolon research: a breakthrough using methods of protein anchoring to membranes

Research Project

Project/Area Number 18H03938
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 38:Agricultural chemistry and related fields
Research InstitutionTohoku University

Principal Investigator

Nakayama Toru  東北大学, 工学研究科, 教授 (80268523)

Co-Investigator(Kenkyū-buntansha) 飯嶋 益巳  東京農業大学, 応用生物科学部, 准教授 (40390728)
山下 哲  金沢大学, 物質化学系, 准教授 (70361186)
黒田 俊一  大阪大学, 産業科学研究所, 教授 (60263406)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥44,460,000 (Direct Cost: ¥34,200,000、Indirect Cost: ¥10,260,000)
Fiscal Year 2020: ¥13,780,000 (Direct Cost: ¥10,600,000、Indirect Cost: ¥3,180,000)
Fiscal Year 2019: ¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
Fiscal Year 2018: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Keywordsフラボノイド / メタボロン / タンパク質間相互作用 / カルコン異性化酵素類似タンパク質 / カルコン合成酵素 / カルコン異性化酵素 / カルコンイソメラーゼ / リポソーム / シトクロムP450
Outline of Final Research Achievements

Formation of flavonoid metabolons were clarified in several plant species and significance of metabolon formation in metabolite channeling during flavonoid biosynthesis was discussed. CHIL, which is widely conserved among land plants and narrows product specificity of chalcone synthase (CHS), was identified and characterized. Crystal structures of CHS and CHIL were clarified and a structural model of a flavonoid metabolon was built. Membrane proteins were successfully introduced onto nanodiscs, which were subjected to direct observation by means of high-speed AFM. The CHS/CHIL protein complex was also observed by means of high-speed AFM and the results were compared with the structural model.

Academic Significance and Societal Importance of the Research Achievements

フラボノイドは,農業,食品工業,医学・薬学・栄養学領域で極めて重要な天然化合物群である.フラボノイドの生合成において,生合成酵素群が複合体(メタボロン)を形成するものと推定されていたが,実証に乏しかった.本研究では,フラボノイドメタボロンの形成様式を具体的に明らかにし,小胞体膜上に形成されるメタボロン解析に必要な,膜タンパク質のナノディスクへの提示技術の基盤を構築した.また,膜タンパク質のナノディスクへの提示やタンパク質間相互作用を,高速AFMにより直接的に観察した.本研究の成果は,この重要な化合物群の進化的側面の理解や生産制御に重要な知見を提供するものである.

Report

(4 results)
  • 2021 Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (19 results)

All 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (11 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 11 results,  Open Access: 2 results) Presentation (7 results) (of which Invited: 5 results)

  • [Int'l Joint Research] オーボアカデミー大学(フィンランド)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Biochemistry and regulation of aurone biosynthesis2022

    • Author(s)
      Toru Nakayama
    • Journal Title

      ioscience, Biotechnology, and Biochemistry

      Volume: NA Issue: 5 Pages: 557-573

    • DOI

      10.1093/bbb/zbac034

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ゴマリグナン配糖体の生合成経路の全貌解明2020

    • Author(s)
      小埜 栄一郎 村田 純 堀川 学 中山 亨
    • Journal Title

      バイオサイエンスとインダストリー

      Volume: 78 Pages: 386-391

    • NAID

      40022368209

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A conserved strategy of chalcone isomerase-like protein to rectify promiscuous chalcone synthase specificity2020

    • Author(s)
      T. Waki, A. Hoshino, et al.
    • Journal Title

      Nature Communications

      Volume: 11 Issue: 1 Pages: 870-870

    • DOI

      10.1038/s41467-020-14558-9

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 酵素の特異性のあいまいさと植物特化代謝の進化: フラボノイド生合成から示唆されること 特異性を矯正する影武者タンパク質の発見2020

    • Author(s)
      中山 亨,高橋征司,和氣駿之
    • Journal Title

      化学と生物

      Volume: 58 Pages: 354-361

    • NAID

      130008046468

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Managing enzyme promiscuity in plant specialized metabolism: A lesson from flavonoid biosynthesis2020

    • Author(s)
      Waki Toshiyuki、Takahashi Seiji、Nakayama Toru
    • Journal Title

      BioEssays

      Volume: 43 Issue: 3 Pages: 2000164-2000164

    • DOI

      10.1002/bies.202000164

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Crystal structure of chalcone synthase, a key enzyme for isoflavonoid biosynthesis in soybean2020

    • Author(s)
      Imaizumi Riki、Mameda Ryo、Takeshita Kohei、Kubo Hiroki、Sakai Naoki、Nakata Shun、Takahashi Seiji、Kataoka Kunishige、Yamamoto Masaki、Nakayama Toru、Yamashita Satoshi、Waki Toshiyuki
    • Journal Title

      Proteins: Structure, Function, and Bioinformatics

      Volume: 89 Issue: 1 Pages: 126-131

    • DOI

      10.1002/prot.25988

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 酵素の特異性のあいまいさと植物特化代謝の進化: フラボノイド生合成から示唆されること 特異性を矯正する影武者タンパク質の発見2020

    • Author(s)
      中山 亨,高橋征司,和氣駿之
    • Journal Title

      化学と生物

      Volume: 58 Pages: 354-361

    • NAID

      130008046468

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] タンパク質間相互作用によるフラボノイド生合成酵素の活性制御: カルコン合成酵素の特異性あいまいさの矯正2020

    • Author(s)
      和氣駿之、高橋征司、中山 亨
    • Journal Title

      酵素工学ニュース

      Volume: 84 Pages: 27-31

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Physical interactions among flavonoid enzymes in snapdragon and torenia reveal the diversity in the flavonoid metabolon organization of different plant species2018

    • Author(s)
      Naoto Fujino, Natsuki Tenma, Toshiyuki Waki, Keisuke Ito, Yuki Komatsuzaki, Keigo Sugiyama, Tatsuya Yamazaki, Saori Yoshida, Masayoshi Hatayama, Satoshi Yamashita, Yoshikazu Tanaka, Reiko Motohashi, Konstantin Denessiouk, Seiji Takahashi and Toru Nakayama
    • Journal Title

      The Plant Journal

      Volume: 94 Issue: 2 Pages: 372-392

    • DOI

      10.1111/tpj.13864

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Involvement of chalcone reductase in the soybean isoflavone metabolon: identification of GmCHR5, which interacts with 2-hydroxyisoflavanone synthase2018

    • Author(s)
      Mameda Ryo、Waki Toshiyuki、Kawai Yosuke、Takahashi Seiji、Nakayama Toru
    • Journal Title

      The Plant Journal

      Volume: 96 Issue: 1 Pages: 56-74

    • DOI

      10.1111/tpj.14014

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] フラボノイドメタボロン 代謝工学へのインパクト2018

    • Author(s)
      和氣 駿之 高橋 征司 中山  亨
    • Journal Title

      バイオサイエンスとインダストリー

      Volume: 76 Pages: 390-394

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] 植物フラボノイドの生合成と構造的多様性に関する酵素科学的研究2021

    • Author(s)
      中山 亨
    • Organizer
      日本農芸化学会大会2021年度大会(仙台)
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] キンギョソウとベニバナに学ぶ花色発現のフラボノイド酵素科学2021

    • Author(s)
      中山 亨
    • Organizer
      日本農芸化学会東北支部 第156回大会 (山形大学 オンライン開催)
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] イソフラボノイド生合成におけるメタボロン形成2021

    • Author(s)
      中山 亨
    • Organizer
      第94回日本生化学会大会(横浜 オンライン開催)
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] セサミノール配糖体の分解の代謝生理学2021

    • Author(s)
      中山 亨
    • Organizer
      第36回日本ゴマ科学会大会(宮崎 オンライン)
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] フラボノイドの生合成 植物はなぜそれをつくるのか2021

    • Author(s)
      中山 亨
    • Organizer
      ビタミンB研究委員会シンポジウム バイオファクター:そのつくられ方と多彩な健康増進効果
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Enhancer of flavonoid productionの機能と進化2019

    • Author(s)
      中山 亨
    • Organizer
      ビタミンB研究委員会
    • Related Report
      2018 Annual Research Report
  • [Presentation] タンパク質間相互作用を介したカルコン合成酵素の生成物特異性の制御2018

    • Author(s)
      中山 亨
    • Organizer
      酵素補酵素研究会
    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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