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2017 Fiscal Year Annual Research Report

Bioactive secondary metabolites produced by sponge symbiont Entotheonella

Research Project

Project/Area Number 15H03112
Research InstitutionHokkaido University

Principal Investigator

脇本 敏幸  北海道大学, 薬学研究院, 教授 (70363900)

Project Period (FY) 2015-04-01 – 2018-03-31
Keywords海綿動物 / 生物活性物質 / 生合成 / 共生微生物
Outline of Annual Research Achievements

本研究では海綿共生微生物Entotheonellaの二次代謝産物生産能に関して普遍性と多様性について検討することを目的としている。特にTheonellidae科の海綿動物についてこれまで伊豆半島産のTheonella swinhoeiとDiscodermia calyxの検討を行ってきた。しかしながら、他の海域や他の種の海綿動物においてはEntotheonellaによる物質生産能の解析は皆無であった。そこで本研究ではDiscodermia属に属する海綿Discodermia kiiensisについて初年度より解析を進め、主にNRPSで構成される2つの生合成遺伝子クラスターの取得に成功した。また本年度は、Theonella swinhoei由来の生合成遺伝子未知であった代謝産物としてtheonellamideの生合成経路の解明に着手した。Theonellamide類は全合成の報告もないため、生合成模倣経路による全合成を試み、特徴的な部分構造であるヒスチジンブリッジの形成機構について知見を得た。T. swinhoeiにはいくつかの異なるケモタイプの存在が知られており、代表的な例としてpolytheonamide類を含む黄色タイプとtheonellamide類を含む白タイプがある。黄色タイプではすでに詳細なメタゲノム解析が行われているが、白タイプは遺伝子の抽出が困難であったため、メタゲノム解析が遅れてきた。最近になりシングルセル解析が徐々に可能になり、遺伝子情報も得られつつある。今年度は白タイプ由来の生合成遺伝子未同定な代謝産物の解析も進めており、その代表的な代謝産物であるtheonellapeptolideの全合成及び新規類縁体の単離構造決定を達成した。また沖縄で採集したT. swinhoeiより theonellapeptolideの生合成遺伝子の探索を現在進めている。

Research Progress Status

29年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

29年度が最終年度であるため、記入しない。

  • Research Products

    (18 results)

All 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results) Presentation (8 results) (of which Int'l Joint Research: 7 results,  Invited: 8 results) Remarks (1 results)

  • [Int'l Joint Research] ETH Zurich(Switzerland)

    • Country Name
      Switzerland
    • Counterpart Institution
      ETH Zurich
  • [Journal Article] Diastereoselective total synthesis and structural confirmation of surugamide F2018

    • Author(s)
      Kuranaga Takefumi、Fukuba Atsuki、Ninomiya Akihiro、Takada Kentaro、Matsunaga Shigeki、Wakimoto Toshiyuki
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 66 Pages: in press

    • Peer Reviewed
  • [Journal Article] Biosynthetic insights of calyculin- and misakinolide-type compounds in “Candidatus Entotheonella sp.”2018

    • Author(s)
      Uria Agustinus、Piel Joern、Wakimoto Toshiyuki
    • Journal Title

      Methods in Enzymology

      Volume: 604 Pages: in press

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Palmitoyl lactic acid induces adipogenesis and a brown fat-like phenotype in 3T3-L1 preadipocytes2018

    • Author(s)
      Uno Yuka、Yamamoto Hirona、Shuto Takatsuki、Sato Yoshinori、Kuranaga Takefumi、Yazawa Kazunaga、Ono Yasuo、Wakimoto Toshiyuki
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids

      Volume: 1863 Pages: 772~782

    • DOI

      10.1016/j.bbalip.2018.04.003

    • Peer Reviewed
  • [Journal Article] Protein phosphatases 1 and 2A and their naturally occurring inhibitors: current topics in smooth muscle physiology and chemical biology2017

    • Author(s)
      Takai Akira、Eto Masumi、Hirano Katsuya、Takeya Kosuke、Wakimoto Toshiyuki、Watanabe Masaru
    • Journal Title

      The Journal of Physiological Sciences

      Volume: 68 Pages: 1~17

    • DOI

      10.1007/s12576-017-0556-6

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Total Synthesis of Theonellapeptolide Id2017

    • Author(s)
      Kuranaga Takefumi、Enomoto Ayumu、Tan Hui、Fujita Kazuto、Wakimoto Toshiyuki
    • Journal Title

      Organic Letters

      Volume: 19 Pages: 1366~1369

    • DOI

      10.1021/acs.orglett.7b00249

    • Peer Reviewed
  • [Journal Article] Toward the Dark Matter of Natural Products2017

    • Author(s)
      Wakimoto Toshiyuki
    • Journal Title

      The Chemical Record

      Volume: 17 Pages: 1124~1134

    • DOI

      10.1002/tcr.201700009

    • Peer Reviewed
  • [Journal Article] Identification of Pyridinium with Three Indole Moieties as an Antimicrobial Agent2017

    • Author(s)
      Okada Masahiro、Sugita Tomotoshi、Wong Chin Piow、Wakimoto Toshiyuki、Abe Ikuro
    • Journal Title

      Journal of Natural Products

      Volume: 80 Pages: 1205~1209

    • DOI

      10.1021/acs.jnatprod.6b01152

    • Peer Reviewed
  • [Journal Article] Characterization of Giant Modular PKSs Provides Insight into Genetic Mechanism for Structural Diversification of Aminopolyol Polyketides2017

    • Author(s)
      Zhang Lihan、Hashimoto Takuya、Qin Bin、Hashimoto Junko、Kozone Ikuko、Kawahara Teppei、Okada Masahiro、Awakawa Takayoshi、Ito Takuya、Asakawa Yoshinori、Ueki Masashi、Takahashi Shunji、Osada Hiroyuki、Wakimoto Toshiyuki、Ikeda Haruo、Shin-ya Kazuo、Abe Ikuro
    • Journal Title

      Angewandte Chemie International Edition

      Volume: 56 Pages: 1740~1745

    • DOI

      10.1002/anie.201611371

    • Peer Reviewed
  • [Presentation] メタゲノムマイニングによる海綿由来新規天然物の探索2018

    • Author(s)
      脇本敏幸
    • Organizer
      日本薬学会第138会
    • Invited
  • [Presentation] メタゲノムマイニングによる海綿由来新規天然物の探索2017

    • Author(s)
      脇本敏幸
    • Organizer
      理研シンポジウム、高磁場・高感度NMR利活用促進のための天然物分野における日中連携シンポジウム2017
    • Int'l Joint Research / Invited
  • [Presentation] Marine sponge-derived metagenomes/uncultured bacteria - a rich source of novel natural product biosynthetic genes2017

    • Author(s)
      Wakimoto Toshiyuki
    • Organizer
      South China Sea Institute of Oceanology, Chinese Academy of Sciences, China
    • Int'l Joint Research / Invited
  • [Presentation] Marine sponge-derived metagenomes/uncultured bacteria - a rich source of novel natural product biosynthetic genes2017

    • Author(s)
      Wakimoto Toshiyuki
    • Organizer
      Jinan University, College of Pharmacy, China
    • Int'l Joint Research / Invited
  • [Presentation] Marine sponge-derived metagenomes/uncultured bacteria - a rich source of novel natural product biosynthetic genes2017

    • Author(s)
      Wakimoto Toshiyuki
    • Organizer
      International Conference on Marine Biodiversity and Biotechnology, Jakarta, Indonesia
    • Int'l Joint Research / Invited
  • [Presentation] Marine sponge-derived metagenomes/uncultured bacteria - a rich source of novel natural product biosynthetic genes2017

    • Author(s)
      Wakimoto Toshiyuki
    • Organizer
      1st China-Japan Joint Symposium on Natural Product Biosynthesis, Shanghai, China
    • Int'l Joint Research / Invited
  • [Presentation] Activated Chemical Defense of Japanese Marine Sponge Discodermia calyx2017

    • Author(s)
      Wakimoto Toshiyuki
    • Organizer
      ISCE/APACE, Kyoto, Japan
    • Int'l Joint Research / Invited
  • [Presentation] Marine sponge-derived metagenomes/uncultured bacteria - a rich source of novel natural product biosynthetic genes2017

    • Author(s)
      Wakimoto Toshiyuki
    • Organizer
      9th US-Japan Seminar on Natural Product Biosynthesis, UCLA Lake Arrowhead Conference Center, California, USA
    • Int'l Joint Research / Invited
  • [Remarks] 北海道大学大学院薬学研究院天然物化学研究室

    • URL

      http://www.pharm.hokudai.ac.jp/tennen/index.html

URL: 

Published: 2018-12-17  

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