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Exploration of new source for drug screening through the comprehensive analysis of secondary metabolism in super rare actinomycetes

Research Project

Project/Area Number 19K05848
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 38040:Bioorganic chemistry-related
Research InstitutionToyama Prefectural University

Principal Investigator

Igarashi Yasuhiro  富山県立大学, 工学部, 教授 (20285159)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywords希少放線菌 / 二次代謝物 / 生理活性物質 / 多様性 / 新規化合物 / 二次代謝
Outline of Research at the Start

微生物二次代謝物は抗癌剤や代謝調節剤など多様な医薬品へと実用化され,人類の福祉に多大な貢献を果たしている。しかしStreptomyces属放線菌やPenicillium属糸状菌など主要な生産微生物は,徹底的にスクリーニングされたため新規化合物の発見頻度が低下し,FK506,スタチン系薬剤の開発以降,注目に値する新規医薬品の開発には至っていない。他方,これまでに二次代謝能が全く未知の属種が多数残されている。本研究では,医薬探索に有用な新規骨格化合物の取得と新たな創薬資源の開拓を目的として,二次代謝物の研究報告がなされていない希少放線菌群における二次代謝物の網羅的構造解析を行う。

Outline of Final Research Achievements

Actinomycetes have been utilized as a producer of medicines including antibiotics for many years, but discovery of new bioactive compounds from commonly studied actinomycetes is getting more difficult. In this study, based on the assumption that gene distribution for secondary metabolites is different at the genus level, we investigated the secondary metabolism in actinomycete genera from which no bioactive compounds have been reported. As a result, we succeeded in discovering the first natural products from unstudied rare actinomycete genera such as Catellatospora, Krasilnikovia, Pseudosporangium, and Allokutzneria. This result indictates that unstudied genera also possess high potential in secondary metabolism and thus should be considered as an untapped source of new compounds in drug discovery program.

Academic Significance and Societal Importance of the Research Achievements

さまざまな抗生物質が放線菌により生産され,これまで70年以上にわたって感染症治療に役立てられてきた。それ以外にも,抗癌剤,抗寄生虫薬,農業用薬剤など多岐にわたる医農薬が放線菌により生産されている。一方で,長期にわたる探索の結果,分離の容易な放線菌からは新規化合物が得にくくなり,新たな探索源の開拓が求められていた。本研究では新薬探索に有用な微生物群の調査を行い、これまで研究されていない放線菌属が優れた物質生産能をもち、多様な新規化合物を生産することを初めて明らかにした。この知見は、今後の微生物からの医農薬探索において役立つものと考えられる。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (15 results)

All 2022 2021 2020 2019

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 2 results) Presentation (6 results)

  • [Journal Article] Plant growth-promoting and antimicrobial chloropyrroles from a rare actinomycete of the genus Catellatospora2022

    • Author(s)
      C. Liu, H. Yamamura, M. Hayakawa, Z. Zhang, N. Oku, Y. Igarashi
    • Journal Title

      Journal of Antibiotics

      Volume: 75 Issue: 12 Pages: 655-661

    • DOI

      10.1038/s41429-022-00567-x

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cyclic enaminones and a?4-quinazolinone from an unidentified actinomycete of the family Micromonosporaceae2022

    • Author(s)
      Triningsih Desy W.、Zhou Tao、Fukaya Keisuke、Harunari Enjuro、Oku Naoya、Urabe Daisuke、Igarashi Yasuhiro
    • Journal Title

      The Journal of Antibiotics

      Volume: 75 Issue: 11 Pages: 610-618

    • DOI

      10.1038/s41429-022-00558-y

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bisprenyl naphthoquinone and chlorinated calcimycin congener bearing thiazole ring from an actinomycete of the genus Phytohabitans2022

    • Author(s)
      Harunari Enjuro、Mae Shunsuke、Fukaya Keisuke、Tashiro Etsu、Urabe Daisuke、Igarashi Yasuhiro
    • Journal Title

      The Journal of Antibiotics

      Volume: 75 Issue: 10 Pages: 542-551

    • DOI

      10.1038/s41429-022-00559-x

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Trehangelin E, a bisacyl trehalose with plant growth promoting activity from a rare actinomycete Polymorphospora sp. RD0644832022

    • Author(s)
      S. Lu, E. Harunari, N. Oku, Y. Igarashi
    • Journal Title

      Journal of Antibiotics

      Volume: 75 Issue: 5 Pages: 296-300

    • DOI

      10.1038/s41429-022-00519-5

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Catellatolactams A?C, Plant Growth-Promoting Ansamacrolactams from a Rare Actinomycete of the Genus <i>Catellatospora</i>2022

    • Author(s)
      Liu Chang、Zhang Zhiwei、Fukaya Keisuke、Urabe Daisuke、Harunari Enjuro、Oku Naoya、Igarashi Yasuhiro
    • Journal Title

      Journal of Natural Products

      Volume: 85 Issue: 8 Pages: 1993-1999

    • DOI

      10.1021/acs.jnatprod.2c00331

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phytohabitols A-C, δ-lactone-terminated polyketides from an actinomycete of the genus Phytohabitans2022

    • Author(s)
      S. Saito, Y. Xiaohanyao, T. Zhou, J. Nakajima-Shimada, E. Tashiro, D. W. Triningsih, E. Harunari, N. Oku, Y. Igarashi
    • Journal Title

      Journal of Natural Products

      Volume: 85 Issue: 7 Pages: 1697-1703

    • DOI

      10.1021/acs.jnatprod.2c00137

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mycetoindole, an N-acyl dehydrotryptophan with plant growth inhibitory activity from an actinomycete of the genus Actinomycetospora2021

    • Author(s)
      Saito Shun、Oku Naoya、Igarashi Yasuhiro
    • Journal Title

      The Journal of Antibiotics

      Volume: 75 Issue: 1 Pages: 44-47

    • DOI

      10.1038/s41429-021-00474-7

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Unsaturated fatty acids and a prenylated tryptophan derivative from a rare actinomycete of the genus <i>Couchioplanes</i>2021

    • Author(s)
      Saito Shun、Indo Kanji、Oku Naoya、Komaki Hisayuki、Kawasaki Masashi、Igarashi Yasuhiro
    • Journal Title

      Beilstein Journal of Organic Chemistry

      Volume: 17 Pages: 2939-2949

    • DOI

      10.3762/bjoc.17.203

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A cyclopeptide and three oligomycin-class polyketides produced by an underexplored actinomycete of the genus Pseudosporangium2020

    • Author(s)
      S. Satio, K. Atsumi, T. Zhou, K. Fukaya, D. Urabe, N. Oku, Md. R. U. Karim, H. Komaki, Y. Igarashi
    • Journal Title

      Beilstain Journal of Organic Chemistry

      Volume: 16 Pages: 1100-1110

    • DOI

      10.3762/bjoc.16.97

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 属レベルで未研究の放線菌における二次代謝能の解析2022

    • Author(s)
      五十嵐 康弘, 斎藤 駿, 春成 円十朗、奥 直也
    • Organizer
      第36回日本放線菌学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Krasilnikolides A-C, cytotoxic 20-membered macrolides from a rare actinomycete of the genus Krasilnikovia2022

    • Author(s)
      S. Lu, T. Zhou, K. Fukaya, E. Harunari, N. Oku, D. Urabe, Y. Igarashi
    • Organizer
      第36回日本放線菌学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Study on taxonomy of an unidentified actinomycete and its new metabolites: cyclic enaminones and a quinazolinone2022

    • Author(s)
      D. W. Triningsih, T. Zhou, K. Fukaya, E. Harunari, N. Enomoto, M. Hamada, N. Oku, D. Urabe, Y. Igarashi
    • Organizer
      第36回日本放線菌学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Three ansamacrolactams and two chlorinated pyrroles with plant growth-promoting activity from two Catellatospora strains2022

    • Author(s)
      C. Liu, Z. Zhang, K. Fukaya, D. Urabe, H. Yamamura, M. Hayakawa, N. Oku, E. Harunari, Y. Igarashi
    • Organizer
      第36回日本放線菌学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 希少放線菌Couchioplanes属が生産する二次代謝物の解析研究2021

    • Author(s)
      齋藤駿、印藤寛二、奥直也、小牧久幸、五十嵐康弘
    • Organizer
      第35回日本放線菌学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 未研究希少放線菌Pseudosporangium属が生産する二次代謝物の精密解析2019

    • Author(s)
      齋藤駿、渥美幸大、深谷圭介、占部大介、小牧久幸、五十嵐康弘
    • Organizer
      日本放線菌学会大会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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