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Structure-activity relationship of lariatin

Research Project

Project/Area Number 23510282
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Chemical biology
Research InstitutionKitasato University

Principal Investigator

INOKOSHI Junji  北里大学, 薬学部, 准教授 (30151640)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords抗結核活性 / 構造活性相関 / 感染症 / 抗生物質 / ペプチド / 蛋白質
Research Abstract

Lariatins A and B discovered as an anti-mycobacterial peptides are ribosomally synthesized by Gram positive Rhodococcus jostii. The compounds are unique cyclic peptides, the rigid lasso structure. Production of lariatins in R. jostii is dependent upon a five-gene cluster, larA to larE. We established a simple system of amino acid substitutions of lariatin by R. jostii delta larA, Using this system, mutational scanning of lariatin was carried out. The results showed that three aa residues (G1, R7 and E8) in the circle and three aa residues (W9, V10 and G11) in the threaded segment of the tail are important for lariatin production, and that two aa residues (Y6 and R7) in the circle and four aa residues (7R7, V10, N14 and K17) in the threaded segment of the tail are important for anti-mycobacterial activity. Propeptin biosynthesis gene cluster was identified on the genome of Microbispora rosae. The gene cluster containing the genes corresponding to lar A , B, C and D, but not lar E.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (5 results)

All 2012 Other

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

  • [Journal Article] Molecular cloning of the gene cluster for lariatin biosynthesis of Rhodococcus jostii K01-B01712012

    • Author(s)
      Inokoshi J, Matsuhama M, Miyake M, Ikeda H, Tomoda H
    • Journal Title

      Appl. Microbiol. Biotechnol 2012

      Volume: 95 Pages: 451-460

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular cloning of the gene cluster for lariatin biosynthesis of Rhodococcus jostii K01-B0171.2012

    • Author(s)
      Inokoshi J, Matsuhama M, Miyake M, Ikeda H, Tomoda H.
    • Journal Title

      Appl Microbiol Biotechnol

      Volume: -

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 抗結核活性を示す放線菌由来投げ縄ペプチド・lariatinの生合成機構の解析とアミノ酸置換変異体の構造活性相関2012

    • Author(s)
      猪腰淳嗣 ,供田洋
    • Organizer
      天然薬物の開発と応用シンポジウム
    • Place of Presentation
      大阪
    • Year and Date
      2012-11-01
    • Related Report
      2013 Final Research Report
  • [Presentation] Analysis of essential amino acids in lasso peptide lariatins for anti-mycobacterial activity by single amino acid substitution2012

    • Author(s)
      J. Inokoshi, M. Miyake, Y. Shimizu, H. Tomoda
    • Organizer
      The 6th Korea-Japan Chemical Biology Symposium
    • Place of Presentation
      札幌
    • Year and Date
      2012-01-27
    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [Presentation] 抗結核活性を示す放線菌由来投げ縄ペプチド・lariatin の生合成機構の解析とアミノ酸置換変異体の構造活性相関

    • Author(s)
      猪腰淳嗣, 供田 洋
    • Organizer
      天然薬物の開発と応用シンポジウム
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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