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Mechanism of multi-step posttranslational modification involved in biogenesis of amine dehydrogenase and its application to development of bioactive polycyclic peptides

Research Project

Project/Area Number 16K07691
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied biochemistry
Research InstitutionHiroshima Institute of Technology (2017-2018)
Osaka University (2016)

Principal Investigator

NAKAI Tadashi  広島工業大学, 生命学部, 准教授 (00333344)

Co-Investigator(Kenkyū-buntansha) 岡島 俊英  大阪大学, 産業科学研究所, 准教授 (10247968)
Research Collaborator OOZEKI Toshinori  
KOZAKAI Kazuki  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords翻訳後修飾 / 補酵素の生合成 / ラジカルSAM酵素 / 分子内チオエーテル架橋 / 環状ペプチド / キノヘムプロテイン / ビルトイン型キノン補酵素 / 酵素触媒機構 / 酵素 / 生理活性
Outline of Final Research Achievements

Peptidyl built-in cofactors are produced by posttranslational modification of the cognate enzyme proteins, unlike ordinary cofactors which are mostly bio-synthesized from water soluble vitamins. In this study, we focused on a built-in quinone cofactor-containing enzyme, quinohemoprotein amine dehydrogenase (QHNDH) that contains cysteine tryptophyl quinone (CTQ). The structural genes encoding QHNDH in Gram-negative bacteria constitute a polycistronic operon together with several nearby genes, which are collectively termed qhp. We have biochemically analyzed one of the peripheral genes, Pden_1710, that may be required for the QHNDH biogenesis. Furthermore, we have succeeded in formation of thioether cross-links using substrates with various sequences and multiple cross-linking sites. These results demonstrate that QhpD is useful for development of various polycyclic peptides.

Academic Significance and Societal Importance of the Research Achievements

ペプチド分子内チオエーテル架橋形成酵素QhpDを用いてAla繰り返し配列の環状化と複数架橋形成に成功した。その結果、様々な配列と架橋数を有する架橋ペプチドを作り出すツールとしてQhpDが有用であることが判明した。以上の研究成果に基づいて今後QhpDの改変を行うことで、抗菌活性など様々な生理活性をもつ多環状ペプチドの開発に活用できると期待できる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (13 results)

All 2019 2018 2017 2016 Other

All Presentation (12 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Remarks (1 results)

  • [Presentation] キノヘムプロテイン・アミン脱水素酵素の活性中心サブユニット生合成に関与するセリンプロテアーゼの機能解析2019

    • Author(s)
      大関俊範, 中井忠志, 谷澤克行, 岡島俊英
    • Organizer
      日本農芸化学会2019年度大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ラジカルSAM酵素QhpDのペプチドチオエーテル架橋形成反応によるAla繰り返し配列の環状化と複数架橋形成2018

    • Author(s)
      大関俊範, 小酒井一輝, 中井忠志, 谷澤克行, 岡島俊英
    • Organizer
      第91回 日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ペプチド・チオエーテル架橋形成酵素QhpDによる環状ペプチド形成機構の解明: 基質配列長および配列許容性の解析2018

    • Author(s)
      小酒井一輝, 大関 俊範, 中井忠志, 谷澤克行, 岡島俊英
    • Organizer
      日本農芸化学会2018年度大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 新規環状ペプチドの開発に向けたラジカルSAM酵素QhpDの基質特異性解析2017

    • Author(s)
      小酒井一輝, 中井忠志, 谷澤克行, 岡島俊英
    • Organizer
      日本農芸化学会2017年度大会
    • Place of Presentation
      京都市
    • Year and Date
      2017-03-17
    • Related Report
      2016 Research-status Report
  • [Presentation] 新規環状ペプチドの創出に向けたラジカルSAM酵素QhpDの架橋形成配列長および配列特異性の解析2017

    • Author(s)
      小酒井一輝, 中井忠志, 谷澤克行, 岡島俊英
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Research-status Report
  • [Presentation] ペプチド分子内チオエーテル架橋形成酵素QhpDにおける架橋形成配列長および配列特異性の解析2017

    • Author(s)
      小酒井一輝, 中井忠志, 谷澤克行, 岡島俊英
    • Organizer
      第69回日本生物工学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 分子内チオエーテル架橋を形成するラジカル SAM 酵素 QhpD の基質特異性解析2017

    • Author(s)
      小酒井一輝, 中井忠志, 谷澤克行, 岡島俊英
    • Organizer
      第17回日本蛋白質科学会年会
    • Related Report
      2017 Research-status Report
  • [Presentation] キノヘムプロテイン・アミン脱水素酵素補酵素含有サブユニットの多段階翻訳後修飾の分子機構2017

    • Author(s)
      岡島俊英, 大関俊範, 小酒井一輝, 中井忠志, 谷澤克行
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Reaction mechanism of interpeptidyl thioether cross-links by radical SAM enzyme QhpD2016

    • Author(s)
      Tadashi Nakai, Katsuyuki Tanizawa, Toshihide Okajima
    • Organizer
      The 20th SANKEN International The 15th SANKEN Nanotechnology Symposium
    • Place of Presentation
      大阪市
    • Year and Date
      2016-12-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Analysis of substrate specificity of intrapeptidyl thioether bond forming radical SAM enzyme QhpD2016

    • Author(s)
      Kazuki Kozakai, Tadashi Nakai, Katsuyuki Tanizawa, Toshihide Okajima
    • Organizer
      The 20th SANKEN International The 15th SANKEN Nanotechnology Symposium
    • Place of Presentation
      大阪市
    • Year and Date
      2016-12-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] ペプチド分子内チオエーテル架橋形成酵素QhpDの基質特異性解析2016

    • Author(s)
      小酒井一輝, 中井忠志, 谷澤克行, 岡島俊英
    • Organizer
      第89回 日本生化学会大会
    • Place of Presentation
      仙台市
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
  • [Presentation] Mechanism of sequential formation of intrapeptidyl thioether cross-links by the radical SAM enzyme QhpD2016

    • Author(s)
      Tadashi Nakai, Katsuyuki Tanizawa, and Toshihide Okajima
    • Organizer
      Fifth International Conference on Cofactors & Active Enzyme Molecule 2016
    • Place of Presentation
      Kurobe, Japan
    • Year and Date
      2016-09-04
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Remarks] 生体分子反応科学研究室

    • URL

      http://www.sanken.osaka-u.ac.jp/labs/smb/

    • Related Report
      2017 Research-status Report 2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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