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Engineering Modular-type Polyketide Synthases

Research Project

Project/Area Number 26560428
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Biomolecular chemistry
Research InstitutionThe University of Tokyo

Principal Investigator

Abe Ikuro  東京大学, 薬学研究科(研究院), 教授 (40305496)

Co-Investigator(Kenkyū-buntansha) AWAKAWA Takayoshi  東京大学, 大学院薬学系研究科, 助教 (80609834)
Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsポリケタイド合成酵素 / 生合成 / 遺伝子 / 生合成工学 / 合成生物学 / ポリエン化合物
Outline of Final Research Achievements

The aim of this study is to elucidate the evolutionary relationship of polyketide synthases through comparison of the amino acid sequences of several polyene synthases. The chemical structure of a new precursor of a polyene, tetrafibricin, was determined, and the compound was named neotetrafibricin. The amino acid sequence of neotetrafibricin synthase was compared with other polyene synthases through bioinformatic ways, resulting in the finding of a key motif which determines a starter substrate specificity. In addition, we elucidated the crystal structure of AntE, an enzyme which provides a polyketide synthase with an extender unit. Based on AntE’s structure, we enlarged the range of substrate specificity of AntE, leading to the production of new antimycin compounds. These results will pave the way for future studies to engineer module-type polyketide synthases.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (13 results)

All 2016 2015 2014 Other

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Acknowledgement Compliant: 5 results,  Open Access: 1 results) Presentation (6 results) (of which Invited: 5 results) Remarks (2 results)

  • [Journal Article] Rational control of polyketide extender units by structure-based engineering of a crotonyl-CoA carboxylase/ reductase in antimycin biosynthesis2015

    • Author(s)
      Zhang, L., Mori, T., Zheng, Q., Awakawa, T., Yan, Y., Liu, W., Abe, I.,
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 54 Issue: 45 Pages: 13462-13465

    • DOI

      10.1002/anie.201506899

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Uncovering the unusual D-ring construction in terretonin biosynthesis by collaboration of a multifunctional cytochrome P450 and a unique isomerase2015

    • Author(s)
      Matsuda, Y., Iwabuchi, T., Wakimoto, T., Awakawa, T., Abe, I.
    • Journal Title

      J. Am. Chem. Soc.

      Volume: 137 Issue: 9 Pages: 3393-3401

    • DOI

      10.1021/jacs.5b00570

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Calyculin biogenesis from a pyrophosphate protoxin produced by a sponge symbiont2014

    • Author(s)
      Wakimoto, T., Egami, Y., Nakashima, Y., Wakimoto,Y., Mori, T., Awakawa,T., Ito, T., Kenmoku, H., Asakawa, Y., Piel, J., Abe, I.
    • Journal Title

      Nature Chem. Biol.

      Volume: 10 Issue: 8 Pages: 648-655

    • DOI

      10.1038/nchembio.1573

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Complete biosynthetic pathway of anditomin: nature's sophisticated synthetic route to a complex fungal meroterpenoid2014

    • Author(s)
      Matsuda, Y., Wakimoto, T., Mori, T., Awakawa, T., Abe, I.
    • Journal Title

      J. Am. Chem. Soc.

      Volume: 136 Issue: 43 Pages: 15326-15336

    • DOI

      10.1021/ja508127q

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Crystallization, and preliminary X-ray diffraction analysis of AntE, a crotonyl-CoA carboxylase/reductase from Streptomyces sp. NRRL 22882014

    • Author(s)
      Zhang, L., Chen, J., Mori, T., Yan, Y., Liu, W., Abe, I.
    • Journal Title

      Acta Crystallogr., Sect. F: Struct. Biol. Cryst. Commun.

      Volume: 70 Issue: 6 Pages: 734-737

    • DOI

      10.1107/s2053230x14008371

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 遺伝子解析に基づくポリエン系化合物の立体配置決定法の確立2016

    • Author(s)
      張 驪駻、秦 斌、淡川 孝義、岡田 正弘、脇本 敏幸、阿部 郁朗
    • Organizer
      第136回日本薬学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-03-29
    • Related Report
      2015 Annual Research Report
  • [Presentation] 複雑骨格天然物の生合成マシナリーの解明2015

    • Author(s)
      阿部郁朗
    • Organizer
      日本化学会 第95春季年会 イブニングセッション
    • Place of Presentation
      千葉県船橋市
    • Year and Date
      2015-03-26
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Engineered Biosynthesis of Medicinal Natural Products2014

    • Author(s)
      阿部郁朗
    • Organizer
      2014 Fall Annual Convention of Pharmaceutical Society of Korea
    • Place of Presentation
      Gyeongju, Korea
    • Year and Date
      2014-10-23 – 2014-10-24
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 天然物の生合成工学2014

    • Author(s)
      阿部郁朗
    • Organizer
      第49回天然物化学談話会
    • Place of Presentation
      岡山県倉敷市
    • Year and Date
      2014-07-02 – 2014-07-04
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Biosynthesis of Fungal Meroterpenoids2014

    • Author(s)
      阿部郁朗
    • Organizer
      97th Canadian Chemistry Conference and Exhibition
    • Place of Presentation
      Vancouver, British Columbia, Canada
    • Year and Date
      2014-06-01 – 2014-06-05
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Engineered Biosynthesis of Medicinal Natural Products2014

    • Author(s)
      阿部郁朗
    • Organizer
      9th International Symposium on Chromatography of Natural Products
    • Place of Presentation
      Medical University of Lublin, Lublin, POLAND
    • Year and Date
      2014-05-26 – 2014-05-29
    • Related Report
      2014 Research-status Report
    • Invited
  • [Remarks] 東京大学大学院薬学系研究科天然物化学教室ホームページ

    • URL

      http://www.f.u-tokyo.ac.jp/~tennen/head.htm

    • Related Report
      2015 Annual Research Report
  • [Remarks] 東京大学大学院薬学系研究科天然物化学教室ホームページ

    • URL

      http://www.f.u-tokyo.ac.jp/~tennen/publications.html

    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2017-05-10  

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