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Chemical genetics for understanding structure and function of cell membranes

Research Project

Project/Area Number 25702048
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypePartial Multi-year Fund
Research Field Biomolecular chemistry
Research InstitutionKyoto University

Principal Investigator

Nishimura Shinichi  京都大学, 薬学研究科(研究院), 助教 (30415260)

Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥25,220,000 (Direct Cost: ¥19,400,000、Indirect Cost: ¥5,820,000)
Fiscal Year 2016: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2014: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2013: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Keywords天然物化学 / 生体膜 / 脂質 / 化学遺伝学
Outline of Final Research Achievements

So far, a large number of natural products (around half a million) has been catalogued in databases. They show unique, complex chemical structures, which make themselves as attractive resources for drug candidates and research tools. In this research project, we have worked on natural products with a molecular function of ‘membrane binding’. This is because a variety of chemotypes has been and will be disclosed to have unique interactions with cell membranes. In addition, research tools are requisite for deeper understanding of the cell membrane. Finally, we have to remember that the cell membrane is one of the major targets of antimicrobials. In this project, we discovered several new natural products and revealed their molecular functions. Functions and regulation mechanisms of membrane lipids were investigated using them as chemical tools. In summary, we successfully demonstrated that chemical genetics is a powerful approach for investigating cell membranes.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (33 results)

All 2016 2015 2014 2013 Other

All Int'l Joint Research (6 results) Journal Article (15 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 14 results,  Open Access: 3 results,  Acknowledgement Compliant: 5 results) Presentation (12 results) (of which Int'l Joint Research: 5 results,  Invited: 2 results)

  • [Int'l Joint Research] University of Florida(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] University of Cambridge(英国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Universidad de Salamanca(Spain)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Northwestern University/University of Florida(米国)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] Universidad de Salamanca(Spain)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] University of Cambridge(英国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Tetherin is an exosomal tether.2016

    • Author(s)
      Edgar, J.R., Manna, P.T., Nishimura, S., Banting, G. & Robinson, M.S.
    • Journal Title

      eLife

      Volume: 5

    • DOI

      10.7554/elife.17180

    • NAID

      120005997859

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sterol-dependent membrane association of the marine sponge-derived bicyclic peptide Theonellamide A as examined by 1H NMR2016

    • Author(s)
      Kimberly Cornelio, Rafael Atillo Espiritu, Yasuto Todokoro, Shinya Hanashima, Masanao Kinoshita, Nobuaki Matsumori, Michio Murata, Shinichi Nishimura, Hideaki Kakeya, Minoru Yoshida, Shigeki Matsunaga
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 24 Issue: 21 Pages: 5235-5242

    • DOI

      10.1016/j.bmc.2016.08.043

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Discovery and Total Synthesis of Streptoaminals: Antimicrobial [5,5]-Spirohemiaminals from  the Combined-Culture of Streptomyces nigrescens and Tsukamurella pulmonis.2016

    • Author(s)
      Sugiyama R, Nishimura S, Ozaki T, Asamizu S, Onaka H, Kakeya H.
    • Journal Title

      Angew Chem Int Ed Engl.

      Volume: 55(35) Issue: 35 Pages: 10278-10282

    • DOI

      10.1002/anie.201604126

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Stereochemical assignment and biological evaluation of BE-14106 unveils the importance of one acetate unit for the antifungal activity of polyene macrolactams2016

    • Author(s)
      Fujita, K.; Sugiyama, R.; Nishimura, S.; Ishikawa, N.; Arai, M. A.; Ishibashi, M.; Kakeya, H.
    • Journal Title

      J. Nat. Prod.

      Volume: 79 Issue: 7 Pages: 1877-1880

    • DOI

      10.1021/acs.jnatprod.6b00250

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Asymmetric total synthesis of heronamides A-C: stereochemical confirmation and impact of long-range stereochemical communication on the biological activity.2016

    • Author(s)
      Kanoh, N., Itoh, S., Fujita, K., Sakanishi, K., Sugiyama, R., Terajima, Y., Iwabuchi, Y., Nishimura, S. & Kakeya, H.
    • Journal Title

      Chem. Eur. J.

      Volume: 22 Issue: 25 Pages: 8586-8595

    • DOI

      10.1002/chem.201600569

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Marine sponge cyclic peptide theonellamide A disrupts lipid bilayer integrity without forming distinct membrane pores.2016

    • Author(s)
      1.Espiritu, R. A., Cornelio, K., Kinoshita, M., Matsumori, N., Murata, M., Nishimura, S., Kakeya, H., Yoshida, M. & Matsunaga, S.
    • Journal Title

      Biochim. Biophys. Acta

      Volume: 1858 Issue: 6 Pages: 1373-1379

    • DOI

      10.1016/j.bbamem.2016.03.019

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Susceptibility of outer hair cells to cholesterol chelator 2-hydroxypropyl-β-cyclodextrine is prestin-dependent2016

    • Author(s)
      Satoe Takahashi, Kazuaki Homma, Yingjie Zhou, Shinichi Nishimura, Chongwen Duan, Jessie Chen, Aisha Ahmad, Mary Ann Cheatham & Jing Zheng
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 21973-21973

    • DOI

      10.1038/srep21973

    • NAID

      120005818274

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] In Vivo Linking of Membrane Lipids and the Anion Transporter Band 3 with Thiourea-modified Amphiphilic Lipid Probes2015

    • Author(s)
      Akihiro Moriyama, Naohiro Katagiri, Shinichi Nishimura, Nobuaki Takahashi & Hideaki Kakeya
    • Journal Title

      Scientific Reports

      Volume: 5 Issue: 1 Pages: 17427-17427

    • DOI

      10.1038/srep17427

    • NAID

      120005708010

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 5-Alkyl-1,2,3,4-tetrahydroquinolines, New Membrane-Interacting Lipophilic Metabolites Produced by Combined Culture of Streptomyces nigrescens and Tsukamurella pulmonis.2015

    • Author(s)
      Sugiyama R, Nishimura S, Ozaki T, Asamizu S, Onaka H, Kakeya H.
    • Journal Title

      Org Lett.

      Volume: 印刷中 Issue: 8 Pages: 1918-1921

    • DOI

      10.1021/acs.orglett.5b00607

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 生体膜微小環境への挑戦:膜ステロールに作用する海洋天然物セオネラミド2015

    • Author(s)
      西村慎一, 掛谷秀昭
    • Journal Title

      CSJカレントレビュー「生物活性分子のケミカルバイオロジー」

      Volume: 19 Pages: 102-108

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Balance of exocytosis and endocytosis determines the efficiency of sterol-targeting antibiotics.2014

    • Author(s)
      Nishimura, S., Tokukura, M., Ochi, J., Yoshida, M. & Kakeya H.
    • Journal Title

      Chem. Biol.

      Volume: 21 Issue: 12 Pages: 1690-1699

    • DOI

      10.1016/j.chembiol.2014.10.014

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Structure and biological activity of 8-deoxyheronamide C from a marine-derived Streptomyces sp.: heronamides target saturated hydrocarbon chains in lipid membranes.2014

    • Author(s)
      Sugiyama, R., Nishimura, S., Matsumori, N., Tsunematsu, Y., Hattori, A. & Kakeya, H.
    • Journal Title

      J. Am. Chem. Soc.

      Volume: 136 Issue: 14 Pages: 5209-5212

    • DOI

      10.1021/ja500128u

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Total synthesis of the proposed structure of heronamide C2014

    • Author(s)
      K. Sakanishi, S. Itoh, R. Sugiyama, S. Nishimura, H. Kakeya, Y. Iwabuchi, N. Kanoh
    • Journal Title

      European Journal of Organic Chemistry

      Volume: なし Issue: 7 Pages: 1376-1380

    • DOI

      10.1002/ejoc.201301487

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Visualization of cholesterol-rich membrane domains with fluorescently-labeled theonellamides.2013

    • Author(s)
      Nishimura, S., Ishii, K., Iwamoto, K., Matsunaga, S., Ohno-Iwashita, Y., Sato, S. B., Kakeya, H., Kobayashi, T. & Yoshida, M.
    • Journal Title

      PLOS ONE

      Volume: 8 Issue: 12 Pages: e83716-e83716

    • DOI

      10.1371/journal.pone.0083716

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interaction between the marine sponge cyclic peptide theonellamide A and sterols in lipid bilayers as viewed by surface plasmon resonance and solid state 2H NMR.2013

    • Author(s)
      Espiritu, R. A., Matsumori, N., Murata, M., Nishimura, S., Kakeya, H., Matsunaga, S. & Yoshida, M.
    • Journal Title

      Biochemistry

      Volume: 52 Issue: 14 Pages: 2410-2418

    • DOI

      10.1021/bi4000854

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] 微生物の複合培養で得られる5aTHQとstreptoaminalの構造と機能2016

    • Author(s)
      西村慎一, 杉山龍介, 仲谷崇宏, 尾崎太郎, 浅水俊平, 尾仲宏康, 掛谷秀昭
    • Organizer
      第21回 天然薬物の開発と応用シンポジウム
    • Place of Presentation
      千葉
    • Year and Date
      2016-10-27
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 生体膜と相互作用する5aTHQ類の構造活性相関と蛍光プローブ開発2016

    • Author(s)
      仲谷崇宏、杉山龍介、西村慎一、掛谷秀昭
    • Organizer
      日本ケミカルバイオロジー学会 第11回年会
    • Place of Presentation
      京都
    • Year and Date
      2016-06-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] Strict recognition of membrane lipids by a sea cucumber saponin, holotoxin B2016

    • Author(s)
      Nishimura, S., Ito, A., Kakeya, H.
    • Organizer
      Gordon Research Conference-Marine Natural Products-
    • Place of Presentation
      Ventura, CA, USA
    • Year and Date
      2016-03-06
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] In vivo linking of membrane lipids and membrane proteins using amphiphilic lipid probes2016

    • Author(s)
      Nishimura, S., Moriyama, A., Katagiri, N., Takahashi, N., Kakeya, H.
    • Organizer
      The 8th Takeda Science Foundation Symposium on PharmaSciences: Biomolecule-Based Medicinal Science: Featuring Mid-Size Drugs
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      2016-01-21
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 生体膜に着目した天然有機化合物の機能開拓2016

    • Author(s)
      西村慎一
    • Organizer
      第4回関西バイオ創薬研究会
    • Place of Presentation
      大阪
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Structure and function of heronamides, polyene macrolactams from marine-derived actinomycetes2015

    • Author(s)
      Nishimura, S., Sugiyama, R., Fujita, K., Ito, S., Sakanishi, K., Iwabuchi, Y., Kanoh, N., Matsumori, N., Kakeya, H.
    • Organizer
      The International Chemical Congress of Pacific Basin Societies 2015 (PACIFICHEM 2015)
    • Place of Presentation
      Honolulu, HA, USA
    • Year and Date
      2015-12-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Sterol-targeting antibiotics and the balance of membrane trafficking2015

    • Author(s)
      Nishimura, S., Kakeya, H.
    • Organizer
      The International Chemical Congress of Pacific Basin Societies 2015 (PACIFICHEM 2015)
    • Place of Presentation
      Honolulu, HA, USA
    • Year and Date
      2015-12-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Abnormal cell wall deposition by heronamides, small molecules targeting phospholipids possessing saturated hydrocarbon chain2015

    • Author(s)
      Nishimura, S., Sugiyama, R., Fujita, K., Kakeya, H
    • Organizer
      Pombe 2105 (8th International Fission Yeast Meeting)
    • Place of Presentation
      Kobe, Japan
    • Year and Date
      2015-06-21
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Marine natural products targeting cell membrane.2014

    • Author(s)
      Nishimura, S., Sugiyama, R., Matsumori, N., Kakeya, H.
    • Organizer
      3rd Annual Conference of the International Chemical Biology Society
    • Place of Presentation
      San Francisco
    • Year and Date
      2014-11-17 – 2014-11-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] Mode of action of heronamides, polyene macrolactams from marine-derived Streptomyces sp.2014

    • Author(s)
      Nishimura, S.
    • Organizer
      Gordon Research Conference-Marine Natural Products-
    • Place of Presentation
      CA, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] 抗生物質が好む生体膜の解析2013

    • Author(s)
      西村慎一、徳倉将人、越智純子、吉田稔 & 掛谷秀昭.
    • Organizer
      第6回北陸合同バイオシンポジウム
    • Place of Presentation
      石川
    • Related Report
      2013 Annual Research Report
  • [Presentation] Sterol-rich membrane domains and the balance of membrane traffic2013

    • Author(s)
      Nishimura, S., Tokukura, M., Ochi, J., Yoshida, M. & Kakeya, H.
    • Organizer
      7th International fission Yeast Meeting
    • Place of Presentation
      London, UK
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2022-02-16  

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