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Enhanced production of natural compounds using the potential chemical signal response mechanisms of micro-organisms

Research Project

Project/Area Number 21K19099
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 38:Agricultural chemistry and related fields
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Takahashi Shunji  国立研究開発法人理化学研究所, 環境資源科学研究センター, ユニットリーダー (30311608)

Project Period (FY) 2021-07-09 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywordsケミカルシグナル / 微生物二次代謝産物 / 天然化合物 / 生産誘導 / βーカルボリン / 放線菌 / 転写制御因子 / リベロマイシン
Outline of Research at the Start

本研究では、β-カルボリンに応答する標的分子の作用機序、遺伝子発現制御に関わる未知の分子機構の解明に挑む。更に、放線菌に仕組まれている未知のケミカルシグナル受容機構を解明することによって、多岐にわたる遺伝子操作を行わずに天然化合物生産を誘導する革新手法を開発する。以上により、ポストゲノム時代の最重要課題である「潜在遺伝子資源の化合物資源化」に向けて突破口を切り開く。

Outline of Final Research Achievements

Natural products are widely utilized because of their diverse structures and strong biological activities, and the development of methods to convert the genetic resources hidden in microorganisms into useful compound sources is an important issue in the post-genome era. It is desired to create natural products that can be used as seeds for pharmaceuticals and agrochemicals by activating biosynthetic gene clusters of secondary metabolites that exist in the actinomycete genome. In this study, we have utilized "chemical communication signals" to induce the production of microbial secondary metabolites without genetic modification.

Academic Significance and Societal Importance of the Research Achievements

生物間相互作用に仕組まれているケミカルコミュニケーションシグナルを解明することは、共生の学術的理解に繋がる。二次代謝物生産の潜在能力の開拓、未知遺伝子資源の化合物資源への変換が進展することによって、生命科学・医薬・農業分野への波及が期待される。

Report

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

    (28 results)

All 2023 2022 2021 Other

All Journal Article (12 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 12 results,  Open Access: 3 results) Presentation (15 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (1 results)

  • [Journal Article] Identification and Characterization of Bifunctional Drimenol Synthases of Marine Bacterial Origin2022

    • Author(s)
      Vo Nhu Ngoc Quynh、Nomura Yuhta、Kinugasa Kiyomi、Takagi Hiroshi、Takahashi Shunji
    • Journal Title

      ACS Chemical Biology

      Volume: 17 Issue: 5 Pages: 1226-1238

    • DOI

      10.1021/acschembio.2c00163

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Crystal structures of a 6-dimethylallyltryptophan synthase, IptA: Insights into substrate tolerance and enhancement of prenyltransferase activity2022

    • Author(s)
      Hironori Suemune, Doukan Nishimura, Kenjiro Mizutani, Yusuke Sato, Tomoya Hino, Hiroshi Takagi, Yumi Shiozaki-Sato, Shunji Takahashi*, Shingo Nagano*
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 593 Pages: 144-150

    • DOI

      10.1016/j.bbrc.2022.01.018

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Isolation of new lucilactaene derivatives from P450 monooxygenase and aldehyde dehydrogenase knockout Fusarium sp. RK97-94 strains and their biological activities2022

    • Author(s)
      Abdelhakim IA, Motoyama Takayuki, Nogawa Toshihiko, Mahmud FB, Futamura Yushi, Takahashi Shunji, Osada Hiroyuki
    • Journal Title

      The Journal of Antibiotics

      Volume: ahead of print Issue: 7 Pages: 361-374

    • DOI

      10.1038/s41429-022-00529-3

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Studies on Streptomyces sp. SN-593: reveromycin biosynthesis, β-carboline biomediator activating LuxR family regulator, and construction of terpenoid biosynthetic platform2022

    • Author(s)
      Takahashi Shunji
    • Journal Title

      The Journal of Antibiotics

      Volume: 75 Issue: 8 Pages: 432-444

    • DOI

      10.1038/s41429-022-00539-1

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isolation of new lucilactaene derivatives from P450 monooxygenase and aldehyde dehydrogenase knockout Fusarium sp. RK97-94 strains and their biological activities.2022

    • Author(s)
      Adel I., Motoyama T., Nogawa T., Mahmud F.B., Futamura Y., Takahashi S., and Osada H.
    • Journal Title

      J. Antibiot.

      Volume: -

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] RK-270D and E, Oxindole Derivatives from Streptomyces sp. with Anti-Angiogenic Activity2022

    • Author(s)
      Jang Jun-Pil、Jang Mina、Nogawa Toshihiko、Takahashi Shunji、Osada Hiroyuki、Ahn Jong Seog、Ko Sung-Kyun、Jang Jae-Hyuk
    • Journal Title

      Journal of Microbiology and Biotechnology

      Volume: 32 Issue: 3 Pages: 302-306

    • DOI

      10.4014/jmb.2110.10039

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Dihydrolucilactaene, a Potent Antimalarial Compound from Fusarium sp. RK97-942021

    • Author(s)
      A. Abdelhakim Islam、Bin Mahmud Fauze、Motoyama Takayuki、Futamura Yushi、Takahashi Shunji、Osada Hiroyuki
    • Journal Title

      Journal of Natural Products

      Volume: 85 Issue: 1 Pages: 63-69

    • DOI

      10.1021/acs.jnatprod.1c00677

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Thiolactomide: A New Homocysteine Thiolactone Derivative from Streptomyces sp. with Neuroprotective Activity2021

    • Author(s)
      Jang Jun-Pil、Kwon Min Cheol、Nogawa Toshihiko、Takahashi Shunji、Osada Hiroyuki、Ahn Jong Seog、Ko Sung-Kyun、Jang Jae-Hyuk
    • Journal Title

      Journal of Microbiology and Biotechnology

      Volume: 31 Issue: 12 Pages: 1667-1671

    • DOI

      10.4014/jmb.2108.08015

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The Conserved Colletotrichum spp. Effector Candidate CEC3 Induces Nuclear Expansion and Cell Death in Plants2021

    • Author(s)
      Tsushima Ayako、Narusaka Mari、Gan Pamela、Kumakura Naoyoshi、Hiroyama Ryoko、Kato Naoki、Takahashi Shunji、Takano Yoshitaka、Narusaka Yoshihiro、Shirasu Ken
    • Journal Title

      Frontiers in Microbiology

      Volume: 12

    • DOI

      10.3389/fmicb.2021.682155

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular Basis for Two Stereoselective Diels-Alderases that Produce Decalin Skeletons2021

    • Author(s)
      Fujiyama Keisuke、Kato Naoki、Re Suyong、Kinugasa Kiyomi、Watanabe Kohei、Takita Ryo、Nogawa Toshihiko、Hino Tomoya、Osada Hiroyuki、Sugita Yuji、Takahashi Shunji、Nagano Shingo
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 60 Issue: 41 Pages: 22401-22410

    • DOI

      10.1002/anie.202106186

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 6,9-Dihydroxytetrangulol, a novel angucyclinone antibiotic accumulated in kiqO gene disruptant in the biosynthesis of kinanthraquinone2021

    • Author(s)
      Sakai Katsuyuki、Takao Risa、Koshino Hiroyuki、Futamura Yushi、Osada Hiroyuki、Takahashi Shunji
    • Journal Title

      The Journal of Antibiotics

      Volume: 74 Issue: 9 Pages: 593-595

    • DOI

      10.1038/s41429-021-00442-1

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] 放線菌二次代謝物の生産を増強する小分子バイオメディエーター2021

    • Author(s)
      高橋 俊二、シュレス パンテー、長田 裕之
    • Journal Title

      化学と生物

      Volume: 59 Pages: 176-181

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] Biosynthetic study of verticilactam, a polycyclic macrolactam from Streptomyces2023

    • Author(s)
      Yu ZHENG, Katsuyuki SAKAI, Hiroshi TAKAGI, Yumi SHIOZAKI-SATO, Toshihiko NOGAWA, Shunji TAKAHASHI
    • Organizer
      4th International Conference on Natural Products Discovery and Development in the Genomic Era
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 岡村英治、佐藤(汐﨑)裕美、奥村英夫、熊坂崇、長田裕之、高橋俊二2023

    • Author(s)
      Reveromycin A生合成酵素RevK-RevL複合体モデル構造に基づくRevL変異導入酵素の解析と相互作用領域決定
    • Organizer
      日本農芸化学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Crystal structure analysis of drimenol synthase from marine bacterium.2023

    • Author(s)
      Keisuke FUJIYAMA, Vo Ngoc Quynh NHU, Shunji TAKAHASHI
    • Organizer
      日本農芸化学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] New elasnin derivatives identified by expression of a SARP family regulatory gene.2023

    • Author(s)
      Islam Amin, Jun Ishikawa, Sachiko Masuda, Ken Shirasu, Shunji Takahashi
    • Organizer
      日本農芸化学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Biosynthetic study of verticilactam, a polycyclic macrolactam from Streptomyces2023

    • Author(s)
      Yu ZHENG, Katsuyuki SAKAI, Hiroshi TAKAGI, Yumi SHIOZAKI-SATO, Toshihiko NOGAWA, Shunji TAKAHASHI
    • Organizer
      日本農芸化学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] リベロマイシンA生合成に関わる複合酵素の鍵相互作用残基の同定2022

    • Author(s)
      岡村英治、 佐藤(汐﨑)裕美、奥村英夫、 熊坂崇、長田裕之、高橋俊二
    • Organizer
      日本放線菌学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Identification of elasnin derivatives by expression of regulatory gene2022

    • Author(s)
      Islam A. Abdelhakim, Naoko Kito, Sachiko Masuda, Ken Shirasu, Jun Ishikawa, and Shunji Takahashi
    • Organizer
      日本放線菌学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Discovery of novel bifunctional drimane sesquiterpene synthases from marine bacteria.2022

    • Author(s)
      Nhu Ngoc Quynh Vo, Yuhta Nomura, Kiyomi Kinugasa, Hiroshi Takagi, Yumi Shiozaki-Sato, and Shunji Takahashi
    • Organizer
      天然有機化合物討論会
    • Related Report
      2022 Annual Research Report
  • [Presentation] デカリン合成酵素の阻害剤同定と共結晶構造解析2022

    • Author(s)
      加藤 直樹,藤山 敬介,永野 真吾,高橋 俊二
    • Organizer
      日本農芸化学会
    • Related Report
      2021 Research-status Report
  • [Presentation] ReveromycinA生合成酵素RevKLMのin sillico解析による相互作用予測と実験的検証2022

    • Author(s)
      岡村 英治,佐藤(汐﨑)裕美,奥村 英夫,熊坂 崇, 長田 裕之,高橋 俊二
    • Organizer
      日本農芸化学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Functional characterization of a novel bifunctional drimenol synthase of bacterial origin: A step toward the discovery of drimane sesquiterpenes in bacteria2022

    • Author(s)
      Nhu Ngoc Quynh Vo,Yuhta Nomura,Kiyomi Kinugasa,Hiroshi Takagi,Yumi Shiozaki-Sato,Shunji Takahashi
    • Organizer
      日本農芸化学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Characterization of cytochrome P450 function in verticilactam biosynthesis2022

    • Author(s)
      Yu ZHENG,Hiroshi TAKAGI,Katsuyuki SAKAI,Yumi SHIOZAKI-SATO,Toshihiko NOGAWA, Risa TAKAO,Shunji TAKAHASHI
    • Organizer
      日本農芸化学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Discovery of new lucilactaene derivatives with potent antimalarial activity and their structure-activity relationship2022

    • Author(s)
      Islam Adel Abdelhakim Amin,Fauze Mahmud, Motoyama Takayuki,Nogawa Toshihiko,Futamura Yushi, Takahashi Shunji,Osada Hiroyuki
    • Organizer
      日本農芸化学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 非典型OmpRレスポンスレギュレーターを用いたkinanthraquinone生産改善と生合成中間体の取得2021

    • Author(s)
      高尾 理沙, 坂井 克行, 越野 広雪, 長田 裕之, 高橋 俊二
    • Organizer
      日本放線菌学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 放線菌の二次代謝生合成機構と生産性増強に関する研究2021

    • Author(s)
      高橋 俊二
    • Organizer
      日本放線菌学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Remarks] 天然物生合成研究ユニット

    • URL

      http://www.csrs.riken.jp/jp/labs/npbu/index.html

    • Related Report
      2021 Research-status Report

URL: 

Published: 2021-07-13   Modified: 2024-01-30  

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