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Systematization of microbial bio-vinyl compounds and its application as seed compounds for drug development

Research Project

Project/Area Number 19K05767
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 38020:Applied microbiology-related
Research InstitutionKyoto Institute of Technology

Principal Investigator

Aso Yuji  京都工芸繊維大学, 繊維学系, 教授 (70380590)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2020: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywordsイタコン酸類縁体 / 発酵生産 / 創薬 / ポリマー合成 / バイオビニル / イタコン酸 / 発酵 / ライブラリー / 構造機能相関 / 創薬シード化合物
Outline of Research at the Start

ある種の微生物は末端ビニル基を有する化合物『バイオビニル』を生産する。これらは抗酸化性・抗菌性・抗炎症性・抗腫瘍性など多様な生理活性を併せ持つ。よって、バイオビニルは感染症予防や抗ガン作用など種々の疾病予防機能を有する新規創薬シード化合物として期待される。この多様な生理機能は末端ビニル基に起因すると考えられるが、バイオビニルの構造-活性相関および発酵生産に関する知見はない。そこで本研究では、バイオビニルの体系化(ライブラリー化)、発酵生産システム構築、構造-機能相関解析を通して、バイオビニルを創薬シード化合物として利用するための基盤を確立する。

Outline of Final Research Achievements

A method “DISCOVER” for screening of microbials producing biovinyl compounds based on thiol-ene reaction and Heck reaction was developed. Aspergillus niger S17-5 producing 9-, 10-hydroxyhexylitaconic acids was isolated from a soil using the method. Production of these compounds was enhanced by adding octanoic acid, suggesting that these compounds are synthesized via alkylcitric acid cycle. Especially, 9-hydroxyhexylitaconic acid showed a cytotoxicity against cancer cells HeLa. Copolymers consisting of 10-hydroxyhexylitaconic acid and itaconic acid were synthesized by free radical polymerization. The molecular weight of the resulting polymers was decreased with increase of the number of 10-hydroxyhexylitaconic acid unit.

Academic Significance and Societal Importance of the Research Achievements

本研究は応用微生物学・創薬化学・高分子合成化学を融合する先駆的な試みである。特に、申請者が開発した技術以外にバイオビニル生産菌を選択的に分離する方法はなく、バイオビニルを創薬原料として利用する試みもないため、本研究は優位性と独創性に優れる。また、新規遺伝子・酵素の取得や新規バイオプロセス法の開発(応用微生物学)、新薬の開発や新規予防医療技術の提供(創薬化学)、新規重合法や新規物性ポリマーの開発(高分子合成化学)など、幅広い学術領域への波及効果が期待できる。

Report

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

    (11 results)

All 2022 2020 2019 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (5 results) (of which Invited: 2 results) Remarks (1 results)

  • [Journal Article] Microbial Screening Based on the Mizoroki-Heck Reaction Permits Exploration of Hydroxyhexylitaconic-Acid-Producing Fungi in Soils2020

    • Author(s)
      Sano Mei、Yada Ryoki、Nomura Yusuke、Kusukawa Takahiro、Ando Hiroshi、Matsumoto Keiji、Wada Kazuhito、Tanaka Tomonari、Ohara Hitomi、Aso Yuji
    • Journal Title

      Microorganisms

      Volume: 8 Issue: 5 Pages: 648-648

    • DOI

      10.3390/microorganisms8050648

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biobased Poly(itaconic Acid-co-10-Hydroxyhexylitaconic Acid)s: Synthesis and Thermal Characterization2020

    • Author(s)
      Aso Yuji、Sano Mei、Yada Ryoki、Tanaka Tomonari、Aoki Takashi、Ohara Hitomi、Kusukawa Takahiro、Matsumoto Keiji、Wada Kazuhito
    • Journal Title

      Materials

      Volume: 13 Issue: 12 Pages: 2707-2707

    • DOI

      10.3390/ma13122707

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Itaconic acid derivatives: structure, function, biosynthesis, and perspectives2020

    • Author(s)
      Sano Mei、Tanaka Tomonari、Ohara Hitomi、Aso Yuji
    • Journal Title

      Applied Microbiology and Biotechnology

      Volume: 104 Issue: 21 Pages: 9041-9051

    • DOI

      10.1007/s00253-020-10908-1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A high-throughput screening method based on the Mizoroki-Heck reaction for isolating itaconic acid-producing fungi from soils2019

    • Author(s)
      Sano Mei、Kuroda Hikari、Ohara Hitomi、Ando Hiroshi、Matsumoto Keiji、Aso Yuji
    • Journal Title

      Heliyon

      Volume: 5 Issue: 7 Pages: e02048-e02048

    • DOI

      10.1016/j.heliyon.2019.e02048

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] DISCOVER: A facile structure-based screening method for vinyl compound producing microbes2019

    • Author(s)
      Aso Yuji、Sano Mei、Kuroda Hikari、Ohara Hitomi、Ando Hiroshi、Matsumoto Keiji
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 16007-16007

    • DOI

      10.1038/s41598-019-52518-6

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 微生物産生イタコン酸類縁体の探索とバイオビニルポリマー開発への展開2022

    • Author(s)
      麻生祐司
    • Organizer
      日本接着学会関東支部月例講演会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] バイオビニルモノマーの微生物生産と新規ポリマー合成への展開2022

    • Author(s)
      麻生祐司
    • Organizer
      近畿化学協会重合工学部会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 有機合成反応を利用したビニル化合物生産菌の選択的分離法2020

    • Author(s)
      麻生祐司、佐野芽生、小原仁実、松本圭司、和田一仁
    • Organizer
      日本農芸化学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 佐野芽生、麻生祐司、小原仁実、松本圭司、和田一仁2020

    • Author(s)
      Aspergillus niger S17-5の生産するヒドロキシヘキシルイタコン酸の生理活性評価
    • Organizer
      日本農芸化学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Aspergillus sp. S17-5の産生するヒドロキシヘキシルイタコン酸の構造解析と生理活性評価2019

    • Author(s)
      野村 友佑、佐野 芽生、小原 仁実、和田 一仁、松本 圭司、麻生 祐司
    • Organizer
      日本生物工学会
    • Related Report
      2019 Research-status Report
  • [Remarks] 研究紹介ホームページ

    • URL

      https://yujiaso.wixsite.com/yujiaso

    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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