• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2021 Fiscal Year Annual Research Report

Chemical communications in microbial interactions and development of useful bioactive ligands

Planned Research

Project AreaFrontier research of chemical communications
Project/Area Number 17H06401
Research InstitutionKyoto University

Principal Investigator

掛谷 秀昭  京都大学, 薬学研究科, 教授 (00270596)

Co-Investigator(Kenkyū-buntansha) 井本 正哉  順天堂大学, 大学院医学研究科, 特任教授 (60213253)
西村 慎一  東京大学, 大学院農学生命科学研究科(農学部), 講師 (30415260)
Project Period (FY) 2017-06-30 – 2022-03-31
Keywords化学コミュニケーション / 天然物化学 / 複合培養 / 生物活性リガンド / 生合成
Outline of Annual Research Achievements

微生物が産生する二次代謝産物は、歴史上、有用なケミカルツール分子や創薬シーズになっている。しかし、これら二次代謝産物の本来の化学コミュニケーションに基づいた生物学的意義はほとんど解明されていない。そこで、引き続き、本研究代表者らが見出した新規抗生物質5aTHQs及びSTAMsを生産可能な放線菌Streptomyces sp. HEK616株とTsukamurella pulmonis TP-B0596株の複合培養系に加えて、複数の有用な複合培養系を確立した。特に、T. pulmonis TP-B0596株と放線菌Streptomyces sp. KUSC_F05株との複合培養により、新規環状ヘキサペプチドlongicatenamides A-Dを見出し、その化学構造及び抗菌作用を明らかにした。
さらに、本研究代表者らが開発した高感度ラベル化剤を活用したHighly-sensitive (HS)-advanced Marfey法を応用することで、極微量の化学コミュニケーション分子の検出試薬の開発を行った。すなわち、希少放線菌Saccharothrix sp. A1506株の培養抽出物より、これまで未発見であった希少天然物presaccharothriolide Zと検出試薬との付加体の検出に成功した。Presaccharothriolide Zの化学構造の確定や活性試験のために、presaccharothriolide Zの化学的全合成にも成功した。一方、領域内連携を活用して、新規抗真菌物質の細胞内化学シグナルの解析のためのケミカルジェネティクス的アプローチを行うとともに、がん幹細胞選択的に細胞死を誘導する複数の生物活性リガンドを見出し、詳細な作用機序解析研究を行った。さらに、ショウガ科ウコン由来のポリフェノール化合物であるクルクミンのプロドラッグ型水溶性化合物CMGが腸内フローラを介して、脳・脊髄の炎症を抑制し、多発性硬化症治療に有効であることを明らかにした。また、CMG(TBP1901)が多発性骨髄腫の標準治療薬ボルテゾミブ耐性の多発性骨髄腫において顕著な抗腫瘍効果を示すことを明らかにした。

Research Progress Status

令和3年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和3年度が最終年度であるため、記入しない。

  • Research Products

    (39 results)

All 2022 2021 Other

All Int'l Joint Research (4 results) Journal Article (19 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 19 results,  Open Access: 1 results) Presentation (13 results) (of which Int'l Joint Research: 8 results,  Invited: 3 results) Book (2 results) Remarks (1 results)

  • [Int'l Joint Research] トロント大学(カナダ)

    • Country Name
      CANADA
    • Counterpart Institution
      トロント大学
  • [Int'l Joint Research] スイス連邦工科大学(スイス)

    • Country Name
      SWITZERLAND
    • Counterpart Institution
      スイス連邦工科大学
  • [Int'l Joint Research] プリンストン大学/ジョンズホプキンス大学(米国)

    • Country Name
      U.S.A.
    • Counterpart Institution
      プリンストン大学/ジョンズホプキンス大学
  • [Int'l Joint Research] ライプニッツ天然有機化合物研究所(ドイツ)

    • Country Name
      GERMANY
    • Counterpart Institution
      ライプニッツ天然有機化合物研究所
  • [Journal Article] Development and application of highly sensitive labeling reagents for amino acids2022

    • Author(s)
      Kuranaga, T., Kakeya, H.
    • Journal Title

      Methods in Enzymol.

      Volume: 665 Pages: 105-133

    • DOI

      10.1016/bs.mie.2021.11.004

    • Peer Reviewed
  • [Journal Article] Developing crosslinkers specific for epimerization domain in NRPS initiation modules to evaluate mechanism2022

    • Author(s)
      Kim, W.E., Ishikawa, F., Re, R.N., Suzuki, T., Dohmae, N., Kakeya, H., Tanabe, G., Burkart, M.D.
    • Journal Title

      RSC Chem. Biol.

      Volume: 27 Pages: 312-319

    • DOI

      10.1039/d2cb00005a

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Differential Biosynthesis and Roles of Two Ferrichrome-Type Siderophores, ASP2397/AS2488053 and Ferricrocin, in Acremonium persicinum2022

    • Author(s)
      Asai, Y., Hiratsuka, T., Ueda, M., Kawamura, Y., Asamizu, S., Onaka, H., Arioka, M., Nishimura, S., Yoshida, M.
    • Journal Title

      ACS Chem. Biol.

      Volume: 17 Pages: 207-216

    • DOI

      10.1021/acschembiol.1c00867

    • Peer Reviewed
  • [Journal Article] Targeting hypoxia-inducible factor 1 (HIF-1) signaling with natural products toward cancer chemotherapy.2021

    • Author(s)
      Ikeda, H., Kakeya, H.
    • Journal Title

      J. Antibiot.

      Volume: 74 Pages: 687-695

    • DOI

      10.1038/s41429-021-00451-0

    • Peer Reviewed
  • [Journal Article] Curcumin beta-D-glucuronide modulates an autoimmune model of multiple sclerosis with altered gut microbiota in the ileum and feces2021

    • Author(s)
      Khadka, S., Omura, S., Sato, F., Nishio, K., Kakeya H., Tsunoda, I.
    • Journal Title

      Front. Cell. Infect. Microbiol.

      Volume: - Pages: -

    • DOI

      10.3389/fcimb.2021.772962

    • Peer Reviewed / Open Access
  • [Journal Article] Design, synthesis, and target identification of new hypoxia-induced factor 1 (HIF-1) inhibitors containing 1-alkyl-1H-pyrazole-3-carboxamide moiety2021

    • Author(s)
      Sakai, M., Takahashi, N., Ikeda, H., Furutani, Y., Higuchi, S., Suzuki, T., Dohmae, N., Kobayashi, S., Harada, H., Kojima, S., Matsuura, T., Hattori, A., Kakeya, H.
    • Journal Title

      Bioorg. Med. Chem.

      Volume: - Pages: -

    • DOI

      10.1016/j.bmc.2021.116375

    • Peer Reviewed
  • [Journal Article] Identification and total synthesis of an unstable anticancer macrolide presaccharothriolide Z produced by Saccharothrix sp.2021

    • Author(s)
      Kuranaga, T., Tamura, M., Ikeda, H., Terada, S., Nakagawa, Y., Kakeya, H.
    • Journal Title

      Org. Lett.

      Volume: 23 Pages: 7106-7111

    • DOI

      10.1021/acs.orglett.lc02506

    • Peer Reviewed
  • [Journal Article] An atypical arginine dihydrolase involved in the biosynthesis of cyclic hexapeptide longicatenamides.2021

    • Author(s)
      Liu, C., Hashimoto, J., Kudo, K., Shin-ya, K., Kakeya, H.
    • Journal Title

      Chem. Asian J.

      Volume: 16 Pages: 1382-1387

    • DOI

      10.1002/asia.202100181

    • Peer Reviewed
  • [Journal Article] Amphiol, an antifungal fungal pigment from Pseudogymnoascus sp. PF1464.2021

    • Author(s)
      Fujita, K., Ikuta, M., Nishimura, S., Sugiyama, R., Yoshimura, A., Kakeya, H.
    • Journal Title

      J. Nat. Med.

      Volume: 84 Pages: 986-992

    • DOI

      10.1021/acs.jnatprod.0c01010

    • Peer Reviewed
  • [Journal Article] Retro-aza-Michael reaction of an o-aminophenol adduct in protic solvents inspired by natural products.2021

    • Author(s)
      Takenaka, K., Kaneko, K., Takahashi, N., Nishimura, S., Kakeya, H.
    • Journal Title

      Bioorg. Med. Chem.

      Volume: - Pages: -

    • DOI

      10.1016/j.bmc.2021.116059

    • Peer Reviewed
  • [Journal Article] Curcumin, an inhibitor of p300-HAT activity, suppresses the development of hypertension-induced left ventricular hypertrophy with preserved ejection fraction in dahl rats.2021

    • Author(s)
      Sunagawa, Y., Funamoto, M., Shimizu, K., Shimizu, S., Sari, N., Katanasaka, Y., Miyazaki, N., Kakeya, H., Hasegawa, K., Morimoto, T.
    • Journal Title

      Nutrients

      Volume: 13 Pages: -

    • DOI

      10.3390/nu13082608

    • Peer Reviewed
  • [Journal Article] Design, synthesis, and antifungal activity of 16,17-dihydroheronamide C and ent-heronamide C2021

    • Author(s)
      Kanoh, N., Terashima, R., Nishiyama, H., Terajima, Y., Nagasawa, S., Sasano, Y., Iwabuchi, Y., Saito, H., Egoshi, S., Dodo, K., Sodeoka, M., Pan, C., Ikeuchi, Y., Nishimura, S., Kakeya, H.
    • Journal Title

      J. Org. Chem.

      Volume: 86 Pages: 16249-16258

    • DOI

      10.1021/acs.joc.1c01761

    • Peer Reviewed
  • [Journal Article] Toward the creation of induced pluripotent small (iPS) molecules: Establishment of a modular synthetic strategy to the heronamide C-type polyene macrolactams and their conformational and reactivity analysis.2021

    • Author(s)
      Kanoh, N., Terajima, Y., Tanaka, S., Terashima, R., Nishiyama, H., Nagasawa, S., Sasano, Y., Iwabuchi, Y., Nishimura, S., Kakeya, H.
    • Journal Title

      J. Org. Chem.

      Volume: 86 Pages: 16231-16248

    • DOI

      10.1021/acs.joc.1c01760

    • Peer Reviewed
  • [Journal Article] Chemoproteomics profiling of surfaction-producing nonribosormal peptide synthetases in living bacterial cells.2021

    • Author(s)
      Ishikawa, F., Konno, S., Uchida, C., Suzuki, T., Takashima, K., Dohmae, N., Kakeya, H., Tanabe, G.
    • Journal Title

      Cell Chem. Biol.

      Volume: 28 Pages: 1-12

    • DOI

      10.1016/j.chembiol.2021.05.014

    • Peer Reviewed
  • [Journal Article] Inhibition of efflux pumps aids small-molecule probe-based fluorescence labeling and imaging in the gram-negative bacterium Escherichia coli.2021

    • Author(s)
      Ishikawa, F., Konno, S., Takashima, K., Kakeya, H., Tanabe, G.
    • Journal Title

      Org. Biomol. Chem.

      Volume: 19 Pages: 8906-8911

    • DOI

      10.1039/d1ob01112j

    • Peer Reviewed
  • [Journal Article] Genomic and targeted approachs unveil the cell membrane as a major target of the antifungal cytotoxin amantelide A2021

    • Author(s)
      Elsadek, L.A., Matthews, J.H., Nishimura, S., Nakatani, T., Ito, A., Gu, T., Luo, D., Salvador-Reyes, L.A., Paul, V.J., Kakeya, H., Luesch, H.
    • Journal Title

      ChemBioChem

      Volume: 22 Pages: 1790-1799

    • DOI

      10.1002/cbic.202000685

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Longicatenamides A-D, two diastereomeric pairs of cyclic hexapeptides produced by combined-culture of Streptomyces sp. KUSC_F05 and Tsukamurella pulmonis TP-B0596.2021

    • Author(s)
      Jiang, Y., Matsumoto, T., Kuranaga, T., Lu, S., Wang, W., Onaka, H., Kakeya, H.
    • Journal Title

      J. Antibiot.

      Volume: 74 Pages: 307-316

    • DOI

      10.1038/s41429-020-00400-3

    • Peer Reviewed
  • [Journal Article] Androgen receptor antagonists produced by Streptomyces overcome resistance to enzalutamide2021

    • Author(s)
      Imoto M, Fujimaki T, Saito S, Tashiro E.
    • Journal Title

      J. Antibiot.

      Volume: 74 Pages: 706-716

    • DOI

      10.1038/s41429-021-00453-y

    • Peer Reviewed
  • [Journal Article] 希少放線菌と異属微生物間化学コミュニケーションを活用したケミカルスペース拡充戦略2021

    • Author(s)
      掛谷秀昭
    • Journal Title

      ファインケミカル

      Volume: 50 Pages: 33-39

    • Peer Reviewed
  • [Presentation] Chemical communication research on microbes toward the development of novel antibiotics2022

    • Author(s)
      Kakeya, H.
    • Organizer
      Japan-the Netherlands Microbiology Symposium 2022
    • Int'l Joint Research / Invited
  • [Presentation] Syetematic screening of new microbial metabolites by combined-culture of actinomycetes2022

    • Author(s)
      Watari, S., Kaneko, K., Iwata, S., Nagao, N., Onaka, H., Shinzato, N., Kakeya, H.
    • Organizer
      Japan-the Netherlands Microbiology Symposium 2022
    • Int'l Joint Research
  • [Presentation] LC-MSを用いた中性条件下の好感度アミノ酸分析2021

    • Author(s)
      森本涼太, 松元拓海, 箕手万由里, 柳沢将行, 山田竜太郎, 倉永健史, 掛谷秀昭
    • Organizer
      創薬懇話会 2020
  • [Presentation] がん幹細胞を標的とした抗がん剤シーズの探索研究2021

    • Author(s)
      池田拓慧, 川見美里, 井本正哉, 掛谷秀昭
    • Organizer
      日本ケミカルバイオロジー学会 第15回年会
  • [Presentation] 微生物間化学コミュニケーションの理解・制御と有用生物活性リガンドの開発2021

    • Author(s)
      掛谷秀昭, 倉永健史, 池田拓慧, 西村慎一, 井本正哉
    • Organizer
      新学術領域研究「化学コミュニケーションのフロンティア」・第8回公開シンポジウム
  • [Presentation] 放線菌由来ロンギカテナミドA-Dに関する研究:異属微生物の複合培養による生産、構造決定、生物活性、及び全合成2021

    • Author(s)
      松元拓海, Yulu Jiang, 倉永健史 Shun Lu, Weicheng Wang, 尾仲宏康, 掛谷秀昭
    • Organizer
      第63回天然有機化合物討論会
  • [Presentation] Design, synthesis , and application of highly sensitive labeling reagents inspired by a scarce natural product.2021

    • Author(s)
      Minote, M., Kuranaga, T., Morimoto, R., Pan, C., Ogawa, H., Kakeya, H.
    • Organizer
      PACIFICHEM2021
    • Int'l Joint Research
  • [Presentation] Highly sensitive amino acid labeling reagents inspired by a scarce natural product yaku'amide B2021

    • Author(s)
      Kuranaga, T., Minote, M., Morimoto, R., Pan, C., Ogawa, H., Kakeya, H.
    • Organizer
      PACIFICHEM2021
    • Int'l Joint Research
  • [Presentation] Discovery of longicatenamides A-D produced by combined-culture of Streptomyces sp. KUSC_F05 and Tsukamurella pulmonis TP-B05962021

    • Author(s)
      Matsumoto, T., Jiang, Y., Kuranaga, T., Lu, S., Wang, W., Onaka, H. Kakeya, H.
    • Organizer
      PACIFICHEM2021
    • Int'l Joint Research
  • [Presentation] Miclxin, a novel MIC60 inhibitor, induces apoptosis via mitochondrial stress in beta-catenin mutant tumor cells2021

    • Author(s)
      Ikeda, H., Muroi, M., Kondoh, Y., Ishikawa, S., Kakeya, H., Osada, H., Imoto, M.
    • Organizer
      PACIFICHEM2021
    • Int'l Joint Research
  • [Presentation] Curcumin mooglucuronide (CMG) treatment alters the gut microbiota, regulating an autoimmune model for multiple sclerosis2021

    • Author(s)
      Omura, S., Khadka, S., Sato, F., Nakamura, Y., Nishio, K., Kakeya, H., Tsunoda, I.
    • Organizer
      PACIFICHEM2021
    • Int'l Joint Research
  • [Presentation] Chemical communication research toward the development of new anticancer drugs2021

    • Author(s)
      Kakeya, H.
    • Organizer
      PACIFICHEM2021
    • Int'l Joint Research / Invited
  • [Presentation] Chemical communication research toward the development of novel antibiotics2021

    • Author(s)
      Kakeya, H.
    • Organizer
      PACIFICHEM2021
    • Invited
  • [Book] くすり大図鑑, Newton大図鑑シリーズ2021

    • Author(s)
      掛谷秀昭(監修)
    • Total Pages
      206
    • Publisher
      ニュートンプレス社
    • ISBN
      978-4-315-52480-2
  • [Book] くすりの科学知識-今こそ知っておきたいくすりの効能、しくみ、正しい付き合い方-(増補 第3版)2021

    • Author(s)
      掛谷秀昭(監修)
    • Total Pages
      175
    • Publisher
      ニュートンプレス社
    • ISBN
      978-4-315-52464-2
  • [Remarks] 京都大学大学院薬学研究科 創発医薬科学専攻 システムケモセラピー(制御分子学)分野

    • URL

      https://www.pharm.kyoto-u.ac.jp/sc-molsci/

URL: 

Published: 2022-12-28  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi