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Exploring and functional analysis of peptide ligase orthologs

Research Project

Project/Area Number 16K18692
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Bioorganic chemistry
Research InstitutionHokkaido University

Principal Investigator

Ogasawara Yasushi  北海道大学, 工学研究院, 助教 (20732986)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywordsペプチドリガーゼ / 酵素 / アミド結合 / 天然物 / 疑似ペプチド / 生合成 / 放線菌 / 二次代謝 / シュードペプチド / 抗生物質
Outline of Final Research Achievements

We previously identified a novel amide bond forming enzyme (peptide ligase, PGM1) responsible for the biosynthesis of peptide antibiotic, pheganomycin. In this study, we studied PGM1 orthologs found in actinobacteria. We first analyzed a ortholog (KtmD) responsible for the biosynthesis of previously discovered novel pseudotripeptides, ketomemicins, which possess a C-terminal pseudodipeptide connected with a carbonylmethylene instead of an amide bond. We showed that KtmD was a novel dipeptide ligase catalyzing amide bond formation between amidino-arginine and pseudodipeptides in the final step of biosynthesis. We next examined the biosynthesis of pseudodipeptide structure in ketomemicins and fully characterized the biosynthetic pathway of the pseudodipeptide in vitro. Furthermore, we investigated other orthologs to probe the functions of these genes. We heterologously expressed ortholog-containing gene clusters in Streptomyces lividans and detected several specific metabolites.

Report

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

    (18 results)

All 2018 2017 2016 Other

All Journal Article (5 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results,  Acknowledgement Compliant: 2 results) Presentation (11 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Book (1 results) Remarks (1 results)

  • [Journal Article] 放線菌が生み出した疑似ペプチド化合物2018

    • Author(s)
      小笠原 泰志、大利 徹
    • Journal Title

      KAGAKU TO SEIBUTSU

      Volume: 56 Issue: 2 Pages: 76-78

    • DOI

      10.1271/kagakutoseibutsu.56.76

    • NAID

      130007563335

    • ISSN
      0453-073X, 1883-6852
    • Year and Date
      2018-01-20
    • Related Report
      2017 Annual Research Report
  • [Journal Article] Peptide Epimerization Machineries Found in Microorganisms2018

    • Author(s)
      Ogasawara Yasushi、Dairi Tohru
    • Journal Title

      Front. Microbiol.

      Volume: 9 Pages: 1-9

    • DOI

      10.3389/fmicb.2018.00156

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biosynthesis of Oligopeptides Using ATP-Grasp Enzymes2017

    • Author(s)
      Ogasawara Yasushi、Dairi Tohru
    • Journal Title

      Chemistry

      Volume: 23 Issue: 45 Pages: 10714-10724

    • DOI

      10.1002/chem.201700674

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biosynthesis of the Carbonylmethylene Structure Found in the Ketomemicin Class of Pseudotripeptides2017

    • Author(s)
      J. Kawata, T. Naoe, Y. Ogasawara, and T. Dairi
    • Journal Title

      Angew. Chem. Int. Ed.

      Volume: 56 Issue: 8 Pages: 2026-2029

    • DOI

      10.1002/anie.201611005

    • NAID

      120006383813

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Characterization of three amidinotransferases involved in the biosynthesis of ketomemicins2016

    • Author(s)
      Y. Ogasawara, M. Fujimori, J. Kawata, and T. Dairi
    • Journal Title

      Bioorg. Med. Chem. Lett.

      Volume: 26 Issue: 15 Pages: 3662-3664

    • DOI

      10.1016/j.bmcl.2016.05.090

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] ポリグルタミン酸生合成の解析2018

    • Author(s)
      重松 真由子、小笠原 泰志、大利 徹
    • Organizer
      日本農芸化学会2018年度大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ペプチドの構造に多様性を与える新規酵素の探索2018

    • Author(s)
      小笠原 泰志
    • Organizer
      日本農芸化学会2018年度大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Exploring novel peptide ligase orthologs - Discovery and biosynthetic studies of carbonylmethylene-containing pseudotripeptides ketomemicins2017

    • Author(s)
      Yasushi Ogasawara, Junpei Kawata, Taiki Naoe, Michiko Fujimori, and Tohru Dairi
    • Organizer
      Directing Biosynthesis V
    • Place of Presentation
      Warwick University, Warwick, UK
    • Year and Date
      2017-03-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] ケトメミシンの生合成に関わるアミジノ基転移酵素の機能解析2017

    • Author(s)
      小笠原 泰志、藤盛 道子、川田 純平、大利 徹
    • Organizer
      2017年度日本農芸化学会大会
    • Place of Presentation
      京都女子大学、京都
    • Year and Date
      2017-03-17
    • Related Report
      2016 Research-status Report
  • [Presentation] 放線菌に見出されたペプチドリガーゼオルソログの機能解析2017

    • Author(s)
      藤村 祐子、小笠原 泰志、大利 徹
    • Organizer
      2017年度日本農芸化学会大会
    • Place of Presentation
      京都女子大学、京都
    • Year and Date
      2017-03-17
    • Related Report
      2016 Research-status Report
  • [Presentation] Biosynthesis of the Carbonylmethylene Containing Pseudopeptides, Ketomemicins2017

    • Author(s)
      Yasushi Ogasawara, Junpei Kawata, Taiki Naoe, Michiko Fujimori, and Tohru Dairi
    • Organizer
      2nd US-Japan Seminar on the Biosynthesis of Natural Products For Young Researchers
    • Place of Presentation
      Tokyo Institute of Technology, Tokyo
    • Year and Date
      2017-03-04
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] ケトメミシンにみられるカルボニルメチレン型シュードペプチドの生合成2017

    • Author(s)
      直江 大樹、川田 順平、小笠原 泰志、大利 徹
    • Organizer
      生合成リデザイン第一回若手セミナー
    • Related Report
      2017 Annual Research Report
  • [Presentation] ペプチド系天然化合物 JBIR-78および JBIR95 の生合成研究2017

    • Author(s)
      37.竹田 薫平、見目 晃平、佐藤 康治、小笠原 泰志、新家 一男、大利 徹
    • Organizer
      第59回 天然有機化合物討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] カルボニルメチレン構造を持つシュードトリペプチド(ケトメミシン)の発見と酵素的全合成2016

    • Author(s)
      小笠原 泰志、川田 純平、野池 基義、藤盛 道子、佐藤 康治、降旗 一夫、大利 徹
    • Organizer
      第58回 天然有機化合物討論会
    • Place of Presentation
      東北大学百周年記念会館、仙台
    • Year and Date
      2016-09-14
    • Related Report
      2016 Research-status Report
  • [Presentation] ケトメミシンにみられるシュードペプチド部の生合成解析2016

    • Author(s)
      川田 純平、直江 大樹、小笠原 泰志、大利 徹
    • Organizer
      2016年度 日本放線菌学会大会
    • Place of Presentation
      東京大学 弥生講堂、東京都文京区
    • Year and Date
      2016-09-08
    • Related Report
      2016 Research-status Report
  • [Presentation] 放線菌に見出された新規ペプチドライゲースオルソログの機能解析2016

    • Author(s)
      藤村 祐子、小笠原 泰志、大利 徹
    • Organizer
      平成28年度 日本農芸化学会 北海道支部第2回講演会
    • Place of Presentation
      北海道大学農学部、札幌
    • Related Report
      2016 Research-status Report
  • [Book] ペプチド医薬品のスクリーニング・安定化・製剤化技術2017

    • Author(s)
      小笠原 泰志、大利 徹、他(合計110名)
    • Total Pages
      557
    • Publisher
      技術情報協会
    • ISBN
      9784861046872
    • Related Report
      2017 Annual Research Report
  • [Remarks] 北海道大学応用生物化学研究室ウェブサイト

    • URL

      http://www.eng.hokudai.ac.jp/labo/tre/ABCLab_jp/

    • Related Report
      2017 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2019-03-29  

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