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The molecular and functional generality of the Basidiomycetous siderophore that promotes mycelial growth and fruiting body formation

Research Project

Project/Area Number 20K05866
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 InstitutionNagoya University (2022)
University of Shizuoka (2020-2021)

Principal Investigator

Tsunematsu Yuta  名古屋大学, 生命農学研究科, 准教授 (30629697)

Co-Investigator(Kenkyū-buntansha) 早川 一郎  日本大学, 文理学部, 教授 (20375413)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords担子菌 / 生合成 / 遺伝子改変 / 子実体形成 / シデロフォア / コプリノフェリン / 非リボソーム性ペプチド合成酵素 / 天然物 / キノコ / NRPS / 子実体 / 生理活性分子 / マツタケ
Outline of Research at the Start

先行研究で発見した新規シデロフォア天然物coprinoferrin (CPF)は、ウシグソヒトヨタケにおいて菌糸成長・子実体(きのこ)形成を促進する分子である。その生合成遺伝子クラスターは他の担子菌種においても保存されていたことから、CPF分子の生理機能は担子菌門において普遍的であると予想された。そこで研究項目①として、複数種の担子菌株におけるCPFの生産性を確認し、生理機能(菌糸成長・子実体形成)の共通性を明らかにする。研究項目②として、難栽培性の担子菌種を対象とし、CPF投与による成長促進効果等を評価する。研究項目③として、CPF生合成経路阻害剤を開発し、疫病担子菌防除の可能性を調査する。

Outline of Final Research Achievements

CPF was discovered from a genetically engineered strain of a mushroom, Coprinopsis cinerea. CPF can enhance the growth of mycelium and facilitate fruiting body formation in the life cycle of this fungus through its affinity to bind environmental iron. This study explored the ubiquity of CPF's presence and its bioactive functions in basidiomycetes. Initially, we identified various Coprinopsis species harboring genes responsible for CPF biosynthesis, and Coprinus phlyctidosporus was determined to produce CPF. We achieved total synthesis of CPF, which enabled us to confirm its molecular structure and biological activities unambiguously. Furthermore, functional assessment of the CPF biosynthetic enzyme Cpf1 demonstrated its valuable attributes, including substantial substrate adaptability and the ability to generate diverse molecules.

Academic Significance and Societal Importance of the Research Achievements

本研究では担子菌遺伝子改変をもとに得たオリジナル新規分子「CPF」について、担子菌内での存在・機能の普遍性を調査し、実際にC. cinereaと近縁種でCPF生合成系が保存されていること、一部の種でCPFが産生されることを示した。つまり、CPFは単なる二次代謝産物というよりも、担子菌の複数種で利用される共通した役目を果たす生理活性分子であるといえる。本研究ではその生合成の分子メカニズム解明を行い、興味深い三量体化機構について、一部を明らかにした。今後、CPFのキノコ形成に対する作用解明が進むことで効率的キノコ栽培法の樹立、栽培不能なキノコ種についても栽培化への道が拓かれ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

    (36 results)

All 2023 2022 2021 2020 Other

All Int'l Joint Research (1 results) Journal Article (17 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 17 results,  Open Access: 7 results) Presentation (16 results) (of which Invited: 3 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] Hans Knoell Institute(ドイツ)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Biosynthetic Gene Expression and Tissue Distribution of Diosgenin in Dioscorea japonica2023

    • Author(s)
      Onoda Keita、Kato Mai、Tsunematsu Yuta、Eto Fumihiro、Sato Michio、Yoshioka Yasukiyo、Yoshida Takuya、Tamura Kentaro、Yao Ikuko、Dohra Hideo、Watanabe Kenji、Miyoshi Noriyuki
    • Journal Title

      Journal of Agricultural and Food Chemistry

      Volume: 71 Issue: 10 Pages: 4292-4297

    • DOI

      10.1021/acs.jafc.2c08478

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Discovery of New Cytotoxic Aplaminone Derivatives from the Sea Hare Aplysia kurodai and Elucidation of Their Accumulation from Local Sea Algae through the Food Chain2023

    • Author(s)
      Hioki Yusuke、Sato Tatsuya、Iwao Toyoki、Ikuma Junya、Kawamura Atsushi、Ohyoshi Takayuki、Tsunematsu Yuta、Kita Masaki
    • Journal Title

      European Journal of Organic Chemistry

      Volume: 26 Issue: 12

    • DOI

      10.1002/ejoc.202300084

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of DNA Damage in Mouse Colorectum by Administration of Colibactin-producing Escherichia coli, Isolated from a Patient With Colorectal Cancer2022

    • Author(s)
      NARITA TAKUMI、TSUNEMATSU YUTA、MIYOSHI NORIYUKI、KOMIYA MASAMI、HAMOYA TAKAHIRO、FUJII GEN、YOSHIKAWA YUKO、SATO MICHIO、KAWANISHI MASANOBU、SUGIMURA HARUHIKO、IWASHITA YUJI、TOTSUKA YUKARI、TERASAKI MASARU、WATANABE KENJI、WAKABAYASHI KEIJI、MUTOH MICHIHIRO
    • Journal Title

      In Vivo

      Volume: 36 Issue: 2 Pages: 628-634

    • DOI

      10.21873/invivo.12746

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 1,2,3-Triazine formation mechanism of the fairy chemical 2-azahypoxanthine in the fairy ring-forming fungus Lepista sordida2022

    • Author(s)
      Ito Akinobu、Choi Jae-Hoon、Yokoyama-Maruyama Waki、Kotajima Mihaya、Wu Jing、Suzuki Tomohiro、Terashima Yurika、Suzuki Hyogo、Hirai Hirofumi、Nelson David C.、Tsunematsu Yuta、Watanabe Kenji、Asakawa Tomohiro、Ouchi Hitoshi、Inai Makoto、Dohra Hideo、Kawagishi Hirokazu
    • Journal Title

      Organic & Biomolecular Chemistry

      Volume: 20 Issue: 13 Pages: 2636-2642

    • DOI

      10.1039/d2ob00328g

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Mother-to-infant transmission of the carcinogenic colibactin-producing bacteria2021

    • Author(s)
      Tsunematsu Yuta、Hosomi Koji、Kunisawa Jun、Sato Michio、Shibuya Noriko、Saito Emiko、Murakami Haruka、Yoshikawa Yuko、Iwashita Yuji、Miyoshi Noriyuki、Mutoh Michihiro、Ishikawa Hideki、Sugimura Haruhiko、Miyachi Motohiko、Wakabayashi Keiji、Watanabe Kenji
    • Journal Title

      BMC Microbiology

      Volume: 21 Issue: 1

    • DOI

      10.1186/s12866-021-02292-1

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association of Escherichia coli containing polyketide synthase in the gut microbiota with colorectal neoplasia in Japan2021

    • Author(s)
      Iwasaki Motoki、Kanehara Rieko、Yamaji Taiki、Katagiri Ryoko、Mutoh Michihiro、Tsunematsu Yuta、Sato Michio、Watanabe Kenji、Hosomi Koji、Kakugawa Yasuo、Ikematsu Hiroaki、Hotta Kinichi、Kunisawa Jun、Wakabayashi Keiji、Matsuda Takahisa
    • Journal Title

      Cancer Science

      Volume: 113 Issue: 1 Pages: 277-286

    • DOI

      10.1111/cas.15196

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Toward Engineered Biosynthesis of Drugs in Human Cells2021

    • Author(s)
      Matsuda Shinya、Tsunematsu Yuta、Matsushita Takuma、Ogata Yuji、Hachiya Shihomi、Kishimoto Shinji、Miyoshi Noriyuki、Watanabe Kenji
    • Journal Title

      ChemBioChem

      Volume: 23 Issue: 4 Pages: 1-7

    • DOI

      10.1002/cbic.202100645

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] 担子菌休眠型生合成遺伝子の覚醒による新規天然物の発見とその菌糸成長・子実体形成作用2021

    • Author(s)
      恒松雄太
    • Journal Title

      アグリバイオ

      Volume: 11 Pages: 1063-1067

    • NAID

      40022757906

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Isolation of New Colibactin Metabolites from Wild-Type Escherichia coli and In Situ Trapping of a Mature Colibactin Derivative2021

    • Author(s)
      Zhou Tao、Hirayama Yuichiro、Tsunematsu Yuta、Suzuki Nanami、Tanaka Seiji、Uchiyama Nahoko、Goda Yukihiro、Yoshikawa Yuko、Iwashita Yuji、Sato Michio、Miyoshi Noriyuki、Mutoh Michihiro、Ishikawa Hideki、Sugimura Haruhiko、Wakabayashi Keiji、Watanabe Kenji
    • Journal Title

      Journal of the American Chemical Society

      Volume: 143 Issue: 14 Pages: 5526-5533

    • DOI

      10.1021/jacs.1c01495

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Catalytic mechanism and endo-to-exo selectivity reversion of an octalin-forming natural Diels?Alderase2021

    • Author(s)
      Sato Michio、Kishimoto Shinji、Yokoyama Mamoru、Jamieson Cooper S.、Narita Kazuto、Maeda Naoya、Hara Kodai、Hashimoto Hiroshi、Tsunematsu Yuta、Houk Kendall N.、Tang Yi、Watanabe Kenji
    • Journal Title

      Nature Catalysis

      Volume: 4 Issue: 3 Pages: 223-232

    • DOI

      10.1038/s41929-021-00577-2

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] o-Anisidine Dimer, 2-Methoxy-N4-(2-methoxyphenyl) Benzene-1,4-diamine, in Rat Urine Associated with Urinary bladder Carcinogenesis2021

    • Author(s)
      Kobayashi Takuma、Toyoda Takeshi、Tajima Yuya、Kishimoto Shinji、Tsunematsu Yuta、Sato Michio、Matsushita Kohei、Yamada Takanori、Shimamura Yuko、Masuda Shuichi、Ochiai Masako、Ogawa Kumiko、Watanabe Kenji、Takamura-Enya Takeji、Totsuka Yukari、Wakabayashi Keiji、Miyoshi Noriyuki
    • Journal Title

      Chemical Research in Toxicology

      Volume: 34 Issue: 3 Pages: 912-919

    • DOI

      10.1021/acs.chemrestox.0c00536

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Characterization of Colibactin-Producing <i>Escherichia coli</i> Isolated from Japanese Patients with Colorectal Cancer2020

    • Author(s)
      Yoshikawa Yuko、Tsunematsu Yuta、Matsuzaki Nobuo、Hirayama Yuichiro、Higashiguchi Fumi、Sato Michio、Iwashita Yuji、Miyoshi Noriyuki、Mutoh Michihiro、Ishikawa Hideki、Sugimura Haruhiko、Wakabayashi Keiji、Watanabe Kenji
    • Journal Title

      Japanese Journal of Infectious Diseases

      Volume: 73 Issue: 6 Pages: 437-442

    • DOI

      10.7883/yoken.JJID.2020.066

    • NAID

      130007942237

    • ISSN
      1344-6304, 1884-2836
    • Year and Date
      2020-11-30
    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Specialized Flavoprotein Promotes Sulfur Migration and Spiroaminal Formation in Aspirochlorine Biosynthesis2020

    • Author(s)
      Tsunematsu Yuta、Maeda Naoya、Sato Michio、Hara Kodai、Hashimoto Hiroshi、Watanabe Kenji、Hertweck Christian
    • Journal Title

      Journal of the American Chemical Society

      Volume: 143 Issue: 1 Pages: 206-213

    • DOI

      10.1021/jacs.0c08879

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Uncovering hidden sesquiterpene biosynthetic pathway through expression boost area-mediated productivity enhancement in basidiomycete2020

    • Author(s)
      Asai Shihori、Tsunematsu Yuta、Masuya Takahiro、Otaka Junnosuke、Osada Hiroyuki、Watanabe Kenji
    • Journal Title

      The Journal of Antibiotics

      Volume: 73 Issue: 10 Pages: 721-728

    • DOI

      10.1038/s41429-020-0355-9

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Association between dietary intake and the prevalence of tumourigenic bacteria in the gut microbiota of middle-aged Japanese adults2020

    • Author(s)
      Watanabe Daiki、Murakami Haruka、Ohno Harumi、Tanisawa Kumpei、Konishi Kana、Tsunematsu Yuta、Sato Michio、Miyoshi Noriyuki、Wakabayashi Keiji、Watanabe Kenji、Miyachi Motohiko
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 15221-15221

    • DOI

      10.1038/s41598-020-72245-7

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Elevated levels of proinflammatory volatile metabolites in feces of high fat diet fed KK-Ay mice2020

    • Author(s)
      Uchikawa Misaki、Kato Mai、Nagata Akika、Sanada Shunsuke、Yoshikawa Yuto、Tsunematsu Yuta、Sato Michio、Suzuki Takuji、Hashidume Tsutomu、Watanabe Kenji、Yoshikawa Yuko、Miyoshi Noriyuki
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 5681-5681

    • DOI

      10.1038/s41598-020-62541-7

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genotyping of a gene cluster for production of colibactin and in vitro genotoxicity analysis of Escherichia coli strains obtained from the Japan Collection of Microorganisms2020

    • Author(s)
      Kawanishi Masanobu、Shimohara Chiaki、Oda Yoshimitsu、Hisatomi Yuuta、Tsunematsu Yuta、Sato Michio、Hirayama Yuichiro、Miyoshi Noriyuki、Iwashita Yuji、Yoshikawa Yuko、Sugimura Haruhiko、Mutoh Michihiro、Ishikawa Hideki、Wakabayashi Keiji、Yagi Takashi、Watanabe Kenji
    • Journal Title

      Genes and Environment

      Volume: 42 Issue: 1 Pages: 12-17

    • DOI

      10.1186/s41021-020-00149-z

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 特化代謝:自然界に生きる有機合成化学者の巧みな分子構築戦略2022

    • Author(s)
      恒松雄太
    • Organizer
      第 9 回 ITbM/GTR コンソーシアムワークショップ
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 微生物から学んだ洗練された有機分子構築戦略2022

    • Author(s)
      恒松雄太
    • Organizer
      「生体適合化学の進歩」インタラクティブフォーラム
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 担子菌Coprinopsis属由来化合物lagopodin Bからhitoyol Aへの変換を担う細胞外酵素の探索2022

    • Author(s)
      鈴木 詞也、浅井 しほり、遠藤 瞭太、恒松 雄太、渡辺 賢二
    • Organizer
      日本薬学会第143年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] キノコ由来子実体形成促進分子 coprinoferrin の生合成解明2021

    • Author(s)
      浅井 しほり, 中屋祥大, 高西 潤, 恒松 雄太, 石川文洋, 田邉元三, 礒谷智輝, 早川一郎, 坂倉 彰, 渡辺 賢二
    • Organizer
      日本生薬学会第67回年会
    • Related Report
      2021 Research-status Report
  • [Presentation] キノコを宿主とした担子菌由来生合成遺伝子導入による物質生産法の構築2021

    • Author(s)
      鈴木詞也, 浅井 しほり, 恒松 雄太, 渡辺 賢二
    • Organizer
      日本生薬学会第67回年会
    • Related Report
      2021 Research-status Report
  • [Presentation] 担子菌由来子実体形成促進分子 coprinoferrin の生合成機構解明2021

    • Author(s)
      浅井 しほり, 中屋祥大, 高西 潤, 恒松 雄太, 石川文洋, 田邉元三, 礒谷智輝, 早川一郎, 坂倉 彰, 渡辺 賢二
    • 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] コリバクチン産生菌制御に基づく大腸発がん予防法樹立への挑戦2020

    • Author(s)
      恒松雄太
    • Organizer
      がん予防学術大会2020米子
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] キノコ由来子実体形成促進分子コプリノフェリンの発見2020

    • Author(s)
      高西潤, 恒松雄太, 桝谷貴洋, 礒谷智輝, 早川一郎, 坂倉彰, 渡辺賢二
    • Organizer
      第62回天然有機化合物討論会
    • Related Report
      2020 Research-status Report
  • [Presentation] Diels-Alderase のジアステレオ選択性および生成物阻害回避メカニズムの解明2020

    • Author(s)
      佐藤道大, 岸本真治, Cooper S. Jamieson, 原幸大, 橋本博, 恒松雄太, Houk N. Kendall, Yi Tang, 渡辺賢二
    • Organizer
      第62回天然有機化合物討論会
    • Related Report
      2020 Research-status Report
  • [Presentation] 担子菌キノコを宿主とした生合成遺伝子発現に基づく新規天然物生産系の確立2020

    • Author(s)
      浅井しほり, 恒松雄太, 高西潤, 大高潤之介, 長田裕之, 渡辺賢二
    • Organizer
      糸状菌分子生物学研究会若手の会第8回WS@Web
    • Related Report
      2020 Research-status Report
  • [Presentation] 担子菌キノコを宿主とした生合成遺伝子発現に基づく新規天然物生産系の確立2020

    • Author(s)
      浅井しほり, 恒松雄太, 高西潤, 大高潤之介, 長田裕之, 渡辺賢二
    • Organizer
      日本病院薬剤師会東海ブロック・日本薬学会東海支部合同学術大会2020
    • Related Report
      2020 Research-status Report
  • [Presentation] コリバクチン生産制御に基づく大腸発がん化学予防剤の開発2020

    • Author(s)
      尾形勇二, 石野皓哉, 佐藤道大, 恒松雄太, 渡辺賢二
    • Organizer
      日本農芸化学会2020年度大会
    • Related Report
      2020 Research-status Report
  • [Presentation] キノコ形成促進物質coprinoferrinの担子菌における普遍性証明と生合成解明2020

    • Author(s)
      高西潤, 桝谷貴洋, 恒松雄太, 礒谷智輝, 早川一郎, 坂倉彰, 渡辺賢二
    • Organizer
      日本農芸化学会2020年度大会
    • Related Report
      2020 Research-status Report
  • [Presentation] シデロフォアトリペプチド コプリノフェリンの合成と生物活性2020

    • Author(s)
      礒谷智輝, 早川一郎, 恒松雄太, 高_潤, 浅井しほり, 渡辺賢二, 坂倉彰
    • Organizer
      日本化学会第100春季年会2020
    • Related Report
      2020 Research-status Report
  • [Presentation] Diels-Alderase CghA の全容解明2020

    • Author(s)
      岸本真治, 佐藤道大, Jamieson Cooper, 横山葵, 成田一仁, 前田直哉, 恒松雄太, 原幸大, 橋本博, Houk Kendall N., 渡辺賢二
    • Organizer
      日本農芸化学会2020年度大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 酵素的Diels-Alder反応におけるジアステレオ選択性の制御機構2020

    • Author(s)
      佐藤道大, 岸本真治, Jamieson Cooper, 成田一仁, 前田直哉, 原幸大, 橋本博, 恒松雄太, Houk N. Kendall, Yi Tang, 渡辺賢二
    • Organizer
      日本薬学会第140年会(京都)
    • Related Report
      2020 Research-status Report
  • [Remarks] 研究業績紹介

    • URL

      https://sweb.u-shizuoka-ken.ac.jp/~kenji55-lab/Yuta/index.html

    • Related Report
      2020 Research-status Report
  • [Patent(Industrial Property Rights)] 抗ウイルス活性を有する組成物2021

    • Inventor(s)
      恒松雄太, 渡辺賢二
    • Industrial Property Rights Holder
      恒松雄太, 渡辺賢二
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-009901
    • Filing Date
      2021
    • Related Report
      2020 Research-status Report

URL: 

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

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