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Search for new drug seeds by co-culture method that mimics the growth environment of microorganisms

Research Project

Project/Area Number 20K16024
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 47050:Environmental and natural pharmaceutical resources-related
Research InstitutionChiba University

Principal Investigator

Hara Yasumasa  千葉大学, 大学院薬学研究院, 助教 (10824625)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords共培養 / 微生物資源 / 培養抽出物ライブラリー構築 / 土壌由来放線菌 / 放線菌Nocardia / 放線菌Nocardia属 / 培養抽出物ライブラリー / 放線菌 / 共培養抽出物ライブラリー構築
Outline of Research at the Start

本研究では、同一環境から分離した微生物を2種組み合わせた共培養により、大規模な共培養抽出物ライブラリーを構築し、天然物探索資源の高度化を図る。また、培養抽出物の網羅的分析、種々の生物活性評価から、構築したライブラリーの有用性を評価するとともに、共培養選択的に生産される新規骨格構造および生物活性を有する天然物の探索を実施する。さらに、共培養選択的に生物活性化合物を産生する微生物の組み合わせをモデルとして、共培養選択的に産生される化合物を明らかにするとともに、休眠遺伝子活性化機構を明らかにする。

Outline of Final Research Achievements

In this study, we searched for new natural products and bioactive natural products by using culture methods that mimics the growth environment of microorganisms such as interactions between microorganisms existing in the same soil, and interactions between animal cells (immune cells) and microorganisms including pathogenic microorganisms. As a result, we isolated new natural products with cell death-inducing and anti-inflammatory effects and several known natural products, and analyzed the mechanisms of action of bioactive natural products.

Academic Significance and Societal Importance of the Research Achievements

微生物の天然物産生に関与する休眠状態の遺伝子を活性化することは、新規天然物を探索する上で重要であり、これまでに様々な手法が開発されてきた。本研究では、微生物の生育環境を模倣した培養により新規天然物を見出したことから、本手法が医薬シードに繋がる新規天然物や生物活性天然物を探索するための有用な手法の一つにつながることが期待される。

Report

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

    (31 results)

All 2023 2022 2021 2020

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 1 results) Presentation (23 results) (of which Int'l Joint Research: 6 results,  Invited: 2 results)

  • [Journal Article] A new 1,2-diketone physalin isolated from Physalis minima and TRAIL-resistance overcoming activity of physalins2023

    • Author(s)
      Teruhisa Manome, Yasumasa Hara, Masami Ishibashi
    • Journal Title

      Journal of Natural Medicines

      Volume: 77 Issue: 2 Pages: 370-378

    • DOI

      10.1007/s11418-022-01670-x

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Natural Compounds with BMI1 Promoter Inhibitory Activity from <i>Mammea siamensis</i> and <i>Andrographis paniculata</i>2022

    • Author(s)
      Fujii Kazuki、Hara Yasumasa、Arai Midori A.、Sadhu Samir K.、Ahmed Firoj、Ishibashi Masami
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 70 Issue: 12 Pages: 885-891

    • DOI

      10.1248/cpb.c22-00556

    • ISSN
      0009-2363, 1347-5223
    • Year and Date
      2022-12-01
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Two bioactive compounds, uniformides A and B, isolated from a culture of Nocardia uniformis IFM0856T in the presence of animal cells2022

    • Author(s)
      Hara, Y.; Watanabe, K.; Takaya, A.; Ebihara, I.; Manome, T.; Arai, M. A.; Yaguchi, T.; Ishibashi, M.
    • Journal Title

      Org. Lett.

      Volume: 24 Issue: 27 Pages: 4998-5002

    • DOI

      10.1021/acs.orglett.2c02092

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Corrrection to “Two Bioactive Compounds, Uniformides A and B, Isolated from a Culture of Nocardia uniformis IFM0856T in the Presence of Animal Cells”2022

    • Author(s)
      Yasumasa Hara, Keiichiro Watanabe, Akiko Takaya, Itsuki Ebihara, Teruhisa Manome, Midori A.Arai, Takashi Yaguchi, Masami Ishibashi
    • Journal Title

      Organic Letters

      Volume: 24 Issue: 31 Pages: 5867-5867

    • DOI

      10.1021/acs.orglett.2c02441

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isolation of Ikahonone, 4-Methyl-2,4-dihydroxy-3-pentanone from Bacillus cereus IFM122352022

    • Author(s)
      Ishibashi Masami、Hara Yasumasa、Chiba Mareno、Watanabe Keiichiro
    • Journal Title

      HETEROCYCLES

      Volume: 105 Issue: 1 Pages: 523-523

    • DOI

      10.3987/com-21-s(r)4

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] New polyoxygenated cyclohexenes isolated from Uvaria rufa and cinnamtannin B1 isolated from Nephelium hypoleucum with TRAIL-resistance-overcoming activity2022

    • Author(s)
      Jitrangsri Kritamorn、Hara Yasumasa、Takaya Akiko、Ishibashi Masami
    • Journal Title

      Phytochemistry Letters

      Volume: 52 Pages: 7-9

    • DOI

      10.1016/j.phytol.2022.08.010

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Isolation of various flavonoids with TRAIL resistance-overcoming activity from Blumea lacera2022

    • Author(s)
      Manome Teruhisa、Hara Yasumasa、Ishibashi Masami
    • Journal Title

      Molecules

      Volume: 28 Issue: 1 Pages: 264-264

    • DOI

      10.3390/molecules28010264

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Isolation of peptidolipin NA derivatives from the culture of Nocardia arthritidis IFM10035T in the presence of mouse macrophage cells2022

    • Author(s)
      Yasumasa Hara, Daiki Tanimura, Teruhisa Manome, Midori A. Arai, Takashi Yaguchi, Masami Ishibashi
    • Journal Title

      Heterocycles

      Volume: 104 Issue: 1 Pages: 185-190

    • DOI

      10.3987/com-21-14567

    • NAID

      40022782818

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] Search for new natural products from actinomycetes of the genus Nocardia in the presence of animal cells2023

    • Author(s)
      Yasumasa Hara
    • Organizer
      The 3rd CRI-CGI-Chiba Symposium in Chemistry
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Molecular mechanism of Physalin H to suppress the Agr-quorum sensing system of methicillin-resistant Staphylococcus aureus2023

    • Author(s)
      Junpei Yamaguchi, Teruhisa Manome, Yasumasa Hara, Yuriko Yamazaki, Yuumi Matsuoka, Masami Ishibashi, Akiko Takaya
    • Organizer
      The 3rd CRI-CGI-Chiba Symposium in Chemistry
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Search for natural products with BMI1 promoter inhibitory effect from Andrographis paniculata and Mammea siamensis2023

    • Author(s)
      Kazuki Fujii, Yasumasa Hara, Masami Ishibashi
    • Organizer
      The 3rd CRI-CGI-Chiba Symposium in Chemistry
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Search for natural products from actinomycetes with anti-fungal activity2023

    • Author(s)
      Tomoka Asanuma, Yasumasa Hara, Mareno Chiba, Akiko Takaya, Masami Ishibashi
    • Organizer
      The 3rd CRI-CGI-Chiba Symposium in Chemistry
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 非カルバペネマーゼ産生クレブシエラにおけるメロペネム寛容性機構2023

    • Author(s)
      山中 夏樹, 山口 隼平, 高橋 弘喜, 原 康雅, 石橋 正己, 高屋 明子
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Physalin Hによる黄色ブドウ球菌agrクオラムセンシングシステム抑制機構2023

    • Author(s)
      山口 隼平, 馬目 照久, 原 康雅, 山崎 由里子, 松岡 悠美, 石橋 正己, 高屋 明子
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 同一土壌分離放線菌の共培養等からの抗真菌活性を指標とした天然物の探索2023

    • Author(s)
      浅沼 朋花, 原 康雅, 千葉 まれの, 高屋 明子, 石橋 正己
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Caesalpinia digyna からの BMI1プロモーター阻害作用を示す天然物の探索2023

    • Author(s)
      藤井 一樹, 原 康雅, 高屋 明子, Firoj Ahmed, Samir K. Sadhu, 石橋 正己
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 熱帯植物Xylia kerri等からの関節リウマチ滑膜線維芽細胞の細胞死誘導作用を有する天然物探索2023

    • Author(s)
      原 康雅, 岩田 樹, 藤井 一樹, 松岡 優輝, 高屋 明子, 石橋 正己
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Nocardia属放線菌からの抗炎症天然物の探索2023

    • Author(s)
      三宅 真未, 原 康雅, 渡邊 圭一郎, 高屋 明子, 矢口 貴志, 石橋 正己
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 放線菌Nocardia carnea IFM 12324からの新規天然物の探索と生合成遺伝子解析2023

    • Author(s)
      馬目 照久, 中村 文香, 原 康雅, 高屋 明子, 伴 さやか, 高橋 弘喜, 矢口 貴志, 石橋 正己
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] BMI1プロモーター阻害作用をもつ植物成分の探索研究2022

    • Author(s)
      藤井 一樹,原 康雅,Firoj Amed, Samir K. Sadhu, 石橋 正己
    • Organizer
      第64回天然有機化合物討論会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 動物細胞存在下Nocardia uniformisの培養を用いた生物活性天然物の探索2022

    • Author(s)
      原 康雅,渡邊 圭一郎,高屋 明子,海老原 樹, 馬目 照久,荒井 緑, 矢口 貴志,石橋 正己
    • Organizer
      日本生薬学会第68回年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Physalis minimaからの新規 physalin 探索とその TRAIL 耐性克服作用の作用機序解析2022

    • Author(s)
      馬目 照久,原 康雅,石橋 正己
    • Organizer
      日本生薬学会第68回年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 真菌Trichoderma harzianum IFM 66736等からのがん細胞死を誘導する天然物の探索2022

    • Author(s)
      馬目 照久,末広 航,原 康雅,原田 真至,石橋 正己
    • Organizer
      第9回食品薬学シンポジウム
    • Related Report
      2022 Annual Research Report
  • [Presentation] 抗菌活性を指標とした微生物由来生物活性天然物の探索2021

    • Author(s)
      原 康雅,千葉 まれの,石橋 正己
    • Organizer
      第65回日本薬学会関東支部大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 動物細胞との共培養法による病原性放線菌Nocardia属からの新規天然物の探索2021

    • Author(s)
      原 康雅,矢口 貴志,石橋 正己
    • Organizer
      第63回天然有機化合物討論会
    • Related Report
      2021 Research-status Report
  • [Presentation] 病原性放線菌Nocardia属からの新規天然物の探索2021

    • Author(s)
      原 康雅
    • Organizer
      日本生薬学会第67年会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 病原真菌Aspergillus fumigatusと免疫細胞の共培養法を用いた新規天然物の探索2021

    • Author(s)
      桑原 るり, 原 康雅, 荒井 緑, 矢口 貴志, 石橋 正己
    • Organizer
      第23回天然薬物の開発と応用シンポジウム
    • Related Report
      2021 Research-status Report
  • [Presentation] 病原性放線菌Nocardia arthritidis等と動物細胞との共培養法を用いた天然物の探索2021

    • Author(s)
      原 康雅, 谷村 大樹, 荒井 緑, 矢口 貴志, 石橋 正己
    • Organizer
      第23回天然薬物の開発と応用シンポジウム
    • Related Report
      2021 Research-status Report
  • [Presentation] Search for new natural products from pathogenic actinomycetes of the genus Nocardia by co-culture with animal cells2021

    • Author(s)
      Yasumasa Hara, Midori Arai, Takashi Yaguchi, Masami Ishibashi
    • Organizer
      Pacifichem 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 動物細胞との共培養法による病原性放線菌Nocardia属由来新規生物活性天然物の探索 (2)2021

    • Author(s)
      原 康雅,矢口 貴志,石橋 正己
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Research-status Report
  • [Presentation] Search for new natural products from pathogenic actinomycetes of the genus Nocardia by co-culture with animal cells2020

    • Author(s)
      Yasumasa Hara, Midori A. Arai, Takashi Yaguchi, Masami Ishibashi
    • Organizer
      2nd German-Japanese Joint Symposium on the Biosynthesis of Natural Products
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research

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Published: 2020-04-28   Modified: 2024-01-30  

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