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Identification of biosynthetic gene clusters of bioactive natural products and their producing bacteria based on sponges life cycle

Research Project

Project/Area Number 16H04980
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Aquatic life science
Research InstitutionKitasato University (2018-2019)
The University of Tokyo (2016-2017)

Principal Investigator

Takada Kentaro  北里大学, 海洋生命科学部, 准教授 (90455353)

Co-Investigator(Kenkyū-buntansha) 松永 茂樹  東京大学, 大学院農学生命科学研究科(農学部), 教授 (60183951)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2019: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2018: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Keywords海洋天然物 / 共生微生物 / 生物活性物質 / メタゲノム解析
Outline of Final Research Achievements

Marine sponges have been recognized as critical marine biochemical resources because some sponge-derived natural products are used as research reagents and chemotherapeutic agents. However, the lack of a sufficient supply of bioactive compounds for clinical development has been a problem. In this study, we focus on the sponge life cycle to identify biosynthetic gene clusters of bioactive natural products and their producers. As a result, we found the biosynthetic gene cluster of mycalolides, inhibitors of actin depolymerization, and its producing bacteria. We also revealed that the Mycale sponge inherits symbiotic bacteria producing mycalolides from parents to offspring via microbial transmission.

Academic Significance and Societal Importance of the Research Achievements

本研究は、海洋生物由来の有用物質の生産者および生合成機構を明らかにすることに成功し、創薬における医薬品候補化合物の応用開発に向けた大きな知見を得ることができた。また、活性物質の生産微生物が新規であったことより、海洋には未利用で有用な微生物資源が存在していることを明らかにした。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (22 results)

All 2020 2019 2018 2017 2016

All Journal Article (16 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 16 results,  Open Access: 1 results,  Acknowledgement Compliant: 3 results) Presentation (6 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results)

  • [Journal Article] Metachromins X and Y from a marine sponge Spongia sp. and their effects on cell cycle progression.2020

    • Author(s)
      Hitora Y, Takada K, Ise Y, Woo S.P, Inoue S, Mori N, Takikawa H, Nakamukai S, Okada S, Matsunaga S
    • Journal Title

      Bioorg. Med. Chem.

      Volume: 28 Issue: 2 Pages: 115233-115233

    • DOI

      10.1016/j.bmc.2019.115233

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heptavalinamide A, an Extensively N-Methylated Linear Nonapeptide from a Cyanobacterium Symploca sp. and Development of a Highly Sensitive Analysis of N,N-Dimethylvaline by LCMS2020

    • Author(s)
      Suo R, Watanabe, R, Takada, K, Suzuki T, Oikawa H, Itoi S, Sugita H, Matsunaga S
    • Journal Title

      Org. Lett.

      Volume: 22 Issue: 4 Pages: 1254-1258

    • DOI

      10.1021/acs.orglett.9b04420

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Microsclerodermins N and O, cytotoxic cyclic peptides containing a p-​ethoxyphenyl moiety from a deep-sea marine sponge Pachastrella sp.2020

    • Author(s)
      Tian T, Takada K, Ise. Y, Ohtsuka S, Okada S, Matsunaga S
    • Journal Title

      Tetrahedron

      Volume: 76 Issue: 10 Pages: 130997-130997

    • DOI

      10.1016/j.tet.2020.130997

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Revised Structure of the Cyclic Octapeptide Surugamide A2019

    • Author(s)
      Matsuda Kenichi、Kuranaga Takefumi、Sano Ayae、Ninomiya Akihiro、Takada Kentaro、Wakimoto Toshiyuki
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 67 Issue: 5 Pages: 476-480

    • DOI

      10.1248/cpb.c19-00002

    • NAID

      130007641158

    • ISSN
      0009-2363, 1347-5223
    • Year and Date
      2019-05-01
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Miuramides A and B, Trisoxazole Macrolides from a Mycale sp. Marine Sponge, That Induce a Protrusion Phenotype in Cultured Mammalian Cells2018

    • Author(s)
      Rei Suo, Kentaro Takada, Hisanori Kohtsuka, Yuji Ise, Shigeru Okada, and Shigeki Matsunaga
    • Journal Title

      Journal of Natural Products

      Volume: 81(4) Issue: 4 Pages: 1108-1112

    • DOI

      10.1021/acs.jnatprod.8b00101

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Poecillastrin H, a Chondropsin-type Macrolide with a Conjugated Pentaene Moiety, from a Characella sp. Marine Sponge2018

    • Author(s)
      Rei Suo, Kentaro Takada, Raku Irie, Ryuichi Watanabe, Toshiyuki Suzuki, Yuji Ise, Susumu Ohtsuka, Shigeru Okada, and Shigeki Matsunaga
    • Journal Title

      Journal of Natural Products

      Volume: 81(5) Issue: 5 Pages: 1295-1299

    • DOI

      10.1021/acs.jnatprod.8b00180

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stellatolide H, a cytotoxic peptide lactone from a deep-sea sponge Discodermia sp.2018

    • Author(s)
      Nakamukai Shohei、Takada Kentaro、Furihata Kazuo、Ise Yuji、Okada Shigeru、Morii Yasuhiro、Yamawaki Nobuhiro、Takatani Tomohiro、Arakawa Osamu、Gustafson Kirk R.、Matsunaga Shigeki
    • Journal Title

      Tetrahedron Letters

      Volume: 59 Issue: 26 Pages: 2532-2536

    • DOI

      10.1016/j.tetlet.2018.05.033

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 2.Fukuhara, K., Takada, K.*, Watanabe, R., Suzuki, T., Okada, S., Matsunaga, S.* Colony-wise Analysis of a Theonella swinhoei Marine Sponge with a Yellow Interior Permitted the Isolation of Theonellamide I.2018

    • Author(s)
      2.Fukuhara, K., Takada, K.*, Watanabe, R., Suzuki, T., Okada, S., Matsunaga, S.*
    • Journal Title

      J. Nat. Prod.

      Volume: 81 Issue: 11 Pages: 2595-2599

    • DOI

      10.1021/acs.jnatprod.8b00591

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lactomycins A-C, Dephosphorylated Phoslactomycin Derivatives that Inhibit Cathepsin B, from the Marine-derived Streptomyces sp. ACT2322018

    • Author(s)
      Yi Sun, Rogie Royce Carandang, Yuta Harada, Shigeru Okada, Kazutoshi Yoshitake, Shuichi Asakawa, Yuichi Nogi, Shigeki Matsunaga, Kentaro Takada
    • Journal Title

      Mar. Drugs

      Volume: 16 Issue: 2 Pages: 70-70

    • DOI

      10.3390/md16020070

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Poecillastrin E, F, and G, cytotoxic chondropsin-type macrolides from a marine sponge Poecillastra sp.2018

    • Author(s)
      Raku Irie, Yuki Hitora, Yuji Ise, Shigeru Okada, Kentaro Takada, Shigeki Matsunaga
    • Journal Title

      Tetrahedron

      Volume: 74 Issue: 13 Pages: 1430-1434

    • DOI

      10.1016/j.tet.2018.01.037

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure Revision of Poecillastrin C and the Absolute Configuration of the β-Hydroxyaspartic Acid Residue2017

    • Author(s)
      Raku Irie, Kentaro Takada, Yuji Ise, Susumu Ohtsuka, Shigeru Okada, Kirk R. Gustafson, Shigeki Matsunaga
    • Journal Title

      Org. Lett.

      Volume: 19 Issue: 19 Pages: 5395-5397

    • DOI

      10.1021/acs.orglett.7b02835

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Resolution of the Confusion in the Assignments of Configuration for the Ciliatamides, Acylated Dipeptides2017

    • Author(s)
      Kentaro Takada, Raku Irie, Rei Suo, Shigeki Matsunaga
    • Journal Title

      J. Nat. Prod.

      Volume: 80 Issue: 10 Pages: 2845-2849

    • DOI

      10.1021/acs.jnatprod.7b00684

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dragmacidins G and H, Bisindole Alkaloids Tethered by a Guanidino Ethylthiopyrazine Moiety, from a Lipastrotethya sp. Marine Sponge2016

    • Author(s)
      Hitora, H.; Takada, K.; Ise, Y.; Okada, S.; Matsunaga, S.
    • Journal Title

      Journal of Natural Products

      Volume: 79 Issue: 11 Pages: 2973-2976

    • DOI

      10.1021/acs.jnatprod.6b00710

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Curacin E from the Brittle Star Ophiocoma scolopendrina2016

    • Author(s)
      Ueoka, R.; Hitora, U.; Ito, A.; Yoshida, M.; Okada, S.; Takada, K.; Matsunaga, S.
    • Journal Title

      Journal of Natural Products

      Volume: 79 Issue: 10 Pages: 2754-2757

    • DOI

      10.1021/acs.jnatprod.6b00701

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Yakushinamides, polyoxygenated fatty acid amides that inhibit HDACs and SIRTs, from the marine sponge Theonella swinhoei.2016

    • Author(s)
      Takada K, Imae Y, Ise Y, Ohtsuka S, Ito A, Okada S, Yoshida M, Matsunaga S.
    • Journal Title

      J. Nat. Prod.

      Volume: 79 Issue: 9 Pages: 2384-2390

    • DOI

      10.1021/acs.jnatprod.6b00588

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biosynthetic gene cluster for surugamide A encompasses an unrelated decapeptide, surugamide F2016

    • Author(s)
      Ninomiya, A., Katsuyama, Y., Kuranaga, T., Miyazaki, M., Nogi, Y., Okada, S., Wakimoto, T., Ohnishi, Y., Matsunaga, S., Takada, K.
    • Journal Title

      ChemBioChem

      Volume: 17 Issue: 18 Pages: 1709-1712

    • DOI

      10.1002/cbic.201600350

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 海洋生物の毒を巡る化学コミュニケーション2019

    • Author(s)
      高田健太郎
    • Organizer
      高磁場・高感度NMR利活用促進のための天然物分野シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 海綿動物の細胞毒性物質を生産する共生微生物と伝播機構の解明2019

    • Author(s)
      高田健太郎
    • Organizer
      日本分子生物学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 海綿動物の細胞毒性物質を生産する共生微生物と伝播機構の解明2018

    • Author(s)
      高田健太郎
    • Organizer
      日本農芸化学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Biologically active secondary metabolites from marine-derived actinomycetes2017

    • Author(s)
      Kentaro Takada
    • Organizer
      The JSFS 85th Anniversary-Commemorative International Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Structures and a Function of Surugamides Isolated from Streptomycete2017

    • Author(s)
      Kentaro Takada
    • Organizer
      1st China-Japan Joint Symposium on Natural Product Biosynthesis
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Structures and a function of cyclic peptides isolated from Streptomycete2016

    • Author(s)
      Kentaro Takada
    • Organizer
      15th MaNaPro
    • Place of Presentation
      Ceara, Brazil
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2016-04-21   Modified: 2021-02-19  

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