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Search for bioactive substances from uncultured microorganisms

Research Project

Project/Area Number 19K16394
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 InstitutionHiroshima University

Principal Investigator

YAMANO YOSHI  広島大学, 医系科学研究科(薬), 助教 (70650597)

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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords難培養性微生物 / 難培養微生物 / 天然物 / 生物活性物質 / 天然物化学 / Actinoplanes / 構造解析 / モデル生物
Outline of Research at the Start

難培養性微生物を特殊な培養装置を用いて培養し、そこから薬の元となるような化合物を精製し、その化合物の構造や生体への影響を明らかにする研究を行う。
難培養性微生物とは、これまで一般的に用いられてきた微生物の培養方法では培養できなかった微生物のことを指す。自然界にいる微生物の大部分は難培養性微生物であると言われていることから、難培養性微生物から薬の元を探すことは画期的な新薬の開発につながる可能性がある。

Outline of Final Research Achievements

This research was conducted with the aim of establishing a method to use "difficult-to-culture microbes" as a new source for drug discovery. Despite the importance of these microbes as sources for drug discovery, they had not been utilized previously due to the challenges associated with their cultivation.  A key accomplishment of the study was the creation of the Gichip, a device that enables the isolation and cultivation of microbes under conditions similar to their natural environment. Using the Gichip, dozens of new microbial species were isolated. Whole genome analysis was performed on the isolated bacterial strains, and their potential to produce chemical compounds was assessed.
LC-MS/MS analysis of the microbial cultures was used as a benchmark for the search for new compounds. As a result, a new diketopiperazine compound and a new bianthracene compound were each isolated and structurally analyzed from two different strains.

Academic Significance and Societal Importance of the Research Achievements

本研究では、数多くの新規微生物を分離培養し、その全ゲノム解析を行った。この研究成果から、医薬品探索源としての新規微生物の利用が可能となり、またそのゲノム配列からは未知の化合物や難培養性関連因子の情報を抽出できることから、これらの成果が幅広い研究分野の進展に寄与することが期待される。探索源としての新規微生物は既知・新規の両方の化合物を産生するため、既知化合物の再単離という非効率な結果をもたらすことも予測されるが、本研究ではLC-MS/MS分析を利用し、新規化合物を選択的に単離する手法を確立した。これにより、難培養性微生物から医薬品候補化合物を効率的に取得する研究手法の確立に向けて大きく前進した。

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

    (18 results)

All 2022 2021 2020 2019 Other

All Journal Article (12 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 12 results,  Open Access: 9 results) Presentation (5 results) Remarks (1 results)

  • [Journal Article] Draft Genome Sequence of Paenibacillus sp. Strain L3-i20, Isolated from Soil in Japan2022

    • Author(s)
      Morita Daichi、Yamano Yoshi、Sugimoto Sachiko、Matsunami Katsuyoshi、Kuroda Teruo
    • Journal Title

      Microbiology Resource Announcements

      Volume: 11 Issue: 6

    • DOI

      10.1128/mra.00077-22

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Complete Genome Sequence of Herbiconiux sp. Strain L3-i23 Isolated from Soil in Japan2022

    • Author(s)
      Yajima Miona、Yamano Yoshi、Morita Daichi、Sugimoto Sachiko、Kuroda Teruo、Matsunami Katsuyoshi
    • Journal Title

      Microbiology Resource Announcements

      Volume: 11 Issue: 11

    • DOI

      10.1128/mra.00815-22

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Understanding the Biosynthesis of Paxisterol in Lichen-Derived Penicillium aurantiacobrunneum for Production of Fluorinated Derivatives2022

    • Author(s)
      Yamano Yoshi、Rakotondraibe Harinantenaina L.
    • Journal Title

      Molecules

      Volume: 27 Issue: 5 Pages: 1641-1641

    • DOI

      10.3390/molecules27051641

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Complete Genome Sequence of Actinoplanes sp. Strain L3-i22, Isolated from Soil in Japan2021

    • Author(s)
      Yamano Yoshi、Sugimoto Sachiko、Matsunami Katsuyoshi
    • Journal Title

      Microbiology Resource Announcements

      Volume: 10 Issue: 42

    • DOI

      10.1128/mra.00798-21

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] New Methyl Threonolactones and Pyroglutamates of Spilanthes acmella (L.) L. and Their Bone Formation Activities2020

    • Author(s)
      Retno Widyowati, Melanny Ika Sulistyowaty, Nguyen Hoang Uyen, Sachiko Sugimoto, Yoshi Yamano, Hideaki Otsuka and Katsuyoshi Matsunami
    • Journal Title

      Molecules

      Volume: 25 Issue: 11 Pages: 2500-2510

    • DOI

      10.3390/molecules25112500

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Lasianosides F-I A New Iridoid and Three New Bis-Iridoid Glycosides from the Leaves of Lasianthus verticillatus (Lour.) Merr.2020

    • Author(s)
      Gadah Abdulaziz Al-Hamoud, Raha Saud Orfali, Yoshio Takeda, Sachiko Sugimoto, Yoshi Yamano, Nawal M. Al Musayeib, Omer Ibrahim Fantoukh , Musarat Amina, Hideaki Otsuka and Katsuyoshi Matsunami
    • Journal Title

      Molecules

      Volume: 25 Issue: 12 Pages: 2798-2808

    • DOI

      10.3390/molecules25122798

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Firmosides A and B: two new sucrose ferulates from the aerial parts of Silene firma and evaluation of radical scavenging activities2020

    • Author(s)
      Nguyen Hoang Uyen, Retno Widyowati, Melanny Ika Sulistyowaty, Sachiko Sugimoto, Yoshi Yamano, Susumu Kawakami, Hideaki Otsuka, Katsuyoshi Matsunami
    • Journal Title

      Journal of Natural Medicines

      Volume: 74 Issue: 4 Pages: 796-803

    • DOI

      10.1007/s11418-020-01426-5

    • NAID

      40022344776

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Bignanoside A "A new neolignan glucoside" and bignanoside B "A new iridoid glucoside" from Bignonia binata leaves2020

    • Author(s)
      Basma Khalaf Mahmoud, Mamdouh Nabil Samy, Ashraf Nagee, Elsayed Hameda Usama Ramadan Abdelmohsena, Dina Hajjar, Yoshi Yamano, Sachiko Sugimoto, Katsuyoshi Matsunami, Mohamed Salah Kamela
    • Journal Title

      Phytochemistry Letters

      Volume: 35 Pages: 200-205

    • DOI

      10.1016/j.phytol.2019.12.009

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Eudesmane-type sesquiterpene glycosides: sonneratiosides A-E and eudesmol β-D-glucopyranoside from the leaves of Sonneratia alba.2020

    • Author(s)
      Katsutani, Kazuma; Sachiko Sugimoto; Yoshi Yamano; Hideaki Otsuka; Katsuyoshi Matsunami; Mizuta, Tsutomu.
    • Journal Title

      Journal of Natural Medicines

      Volume: 74 Issue: 1 Pages: 119-126

    • DOI

      10.1007/s11418-019-01353-0

    • NAID

      40022130141

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Isolation of sesquiterpene-amino acid conjugates, Onopornoids A-D, and a flavonoid glucoside from Onopordum alexandrinum2019

    • Author(s)
      Sachiko Sugimoto; Yoshi Yamano; Desoukey, Samar Y.; Katakawa, Kazuaki; Wanas, Amira S.; Hideaki Otsuka; Katsuyoshi Matsunami.
    • Journal Title

      Journal of Natural Products

      Volume: 82 Issue: 6 Pages: 1471-1477

    • DOI

      10.1021/acs.jnatprod.8b00948

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Four New Flavonoids Isolated from the Aerial Parts of Cadaba rotundifolia Forssk. (Qadab)2019

    • Author(s)
      Gadah Abdulaziz Al-Hamoud, Raha Saud Orfali, Sachiko Sugimoto, Yoshi Yamano, Nafee Alothyqi, Ali Mohammed Alzahrani, Katsuyoshi Matsunami.
    • Journal Title

      Molecules

      Volume: 24 Issue: 11 Pages: 2167-2180

    • DOI

      10.3390/molecules24112167

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Lasianosides A-E: iridoid glucosides from the aerial parts of Lasianthus verticillatus (Lour.) Merr2019

    • Author(s)
      Gadah Al-Hamouda, Raha Saud Orfalib, Shagufta Perveen, Kenta Mizuno, Yoshio Takeda, Tatsuo Nehira, Kazuma Masuda, Sachiko Sugimoto, Yoshi Yamano, Hideaki Otsuka, Katsuyoshi Matsunam.
    • Journal Title

      Molecules, 24(21): 3995 (2019)

      Volume: 24 Issue: 21 Pages: 3995-4007

    • DOI

      10.3390/molecules24213995

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Gichipより得られた土壌微生物の代謝産物解析2022

    • Author(s)
      石飛皓輝, 柴田悠斗, 山野喜, 小川順也, 杉本幸子, 松浪勝義
    • Organizer
      第61回中四国支部学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 木下ももこ,杉本幸子,山野喜,小谷仁司,大塚英昭,松浪勝義2020

    • Author(s)
      菊花 (Chrysanthemum indicum Linne) からのNrf2活性化合物の探索
    • Organizer
      第140回年会日本薬学会 (京都)
    • Related Report
      2019 Research-status Report
  • [Presentation] 末田正太,Harinantenaina Liva,杉本幸子,山野喜,大塚英昭,Claudine Aimee Rasolohery,Marcelle Rakotovao,Heriniaina Randriamampionona Razafindrakoto,Saholinirina Marie Hortensia Randrianarivo,松浪 勝義2019

    • Author(s)
      マダガスカル産植物Distephanus trinervis葉部の成分研究
    • Organizer
      第139回年会日本薬学会 (千葉)
    • Related Report
      2019 Research-status Report
  • [Presentation] 網本久美子,長島佳純,山野喜,杉本幸子,山口卓郎,大塚英昭,松浪勝義2019

    • Author(s)
      沖縄県産植物ヒイラギズイナ(Itea oldhamii)のがん細胞増殖抑制活性成分の探索
    • Organizer
      第139回年会日本薬学会 (千葉)
    • Related Report
      2019 Research-status Report
  • [Presentation] 山野喜,権藤一哉,杉本幸子,松浪勝義2019

    • Author(s)
      トランスジェニック線虫を用いたアルツハイマー病治療薬候補化合物の探索
    • Organizer
      日本生薬学会第66回年会 (東京)
    • Related Report
      2019 Research-status Report
  • [Remarks] Generalized isolation chip

    • URL

      https://doi.org/10.6084/m9.figshare.19336745.v4

    • Related Report
      2021 Research-status Report

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

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