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The mechanism regulating the function of a natural cytotoxin

Research Project

Project/Area Number 15K12740
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Biomolecular chemistry
Research InstitutionHokkaido University

Principal Investigator

WAKIMOTO Toshiyuki  北海道大学, 薬学研究院, 教授 (70363900)

Co-Investigator(Renkei-kenkyūsha) EGAMI Yoko  北海道大学, 大学院薬学研究院, 助教 (50758612)
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsCalyculin A / リン酸化 / 脱リン酸化 / 海綿動物 / カリクリンA / 生合成 / 海綿共生微生物 / calyculin A
Outline of Final Research Achievements

Marine sponges are prolific sources of highly potent cytotoxic compounds, some of which are promising as anticancer drugs. However, the potent cytotoxicity would be harmful to the host sponge, because marine sponges are also animals. Therefore, it is possible that the self-resistance and activated defense systems underlie their biosynthetic mechanism. Wound-activated chemical defense systems are prevalent among terrestrial plants. The precursor molecule and the activating enzyme are compartmentalized in the tissue, which is readily disrupted by wounding to accomplish chemical defense. The similar activated defense strategy has also been found in a few marine sponges. In previous study, we obtained calyculin biosynthetic gene cluster from the metagenomic DNA of Japanese marine sponge Discodermia calyx and the deactivating enzyme was also clustered. The aim of this work is to identify the as-yet unknown enzyme involved in the activating process of the precursor molecule.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (32 results)

All 2017 2016 2015 Other

All Journal Article (19 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 19 results,  Acknowledgement Compliant: 16 results,  Open Access: 6 results) Presentation (11 results) (of which Int'l Joint Research: 5 results,  Invited: 11 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Total synthesis of theonellapeptolide Id2017

    • Author(s)
      Kuranaga, T., Enomoto, A., Tan, H., Fujita, K., Wakimoto, T.
    • Journal Title

      Org. Lett.

      Volume: 19 Issue: 6 Pages: 1366-1369

    • DOI

      10.1021/acs.orglett.7b00249

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Toward dark matter of natural products”2017

    • Author(s)
      Wakimoto, T.
    • Journal Title

      Chem. Rec.

      Volume: 17 Issue: 11 Pages: 1124-1134

    • DOI

      10.1002/tcr.201700009

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Characterization of giant modular PKSs provides insight into genetic mechanism for structural diversification of aminopolyol polyketides2017

    • Author(s)
      Zhang, L., Hashimoto, T., Qin, B., Hashimoto, J., Kozone, I., Kawahara, T., Okada, M., Awakawa, T., Ito, T., Asakawa, Y., Ueki, M., Takahashi, S., Osada, H., Wakimoto, T., Ikeda, H., Shin-ya, K., Abe, I.
    • Journal Title

      Angew. Chem. Int. Ed.

      Volume: 56 Issue: 7 Pages: 1740-1745

    • DOI

      10.1002/anie.201611371

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Identification of pyridinium with three indole moieties as an antimicrobial agent2017

    • Author(s)
      Okada, M., Sugita, T., Wong, C. P., Wakimoto, T., Abe, I.
    • Journal Title

      J. Nat. Prod.,

      Volume: 80 Issue: 4 Pages: 1205-1209

    • DOI

      10.1021/acs.jnatprod.6b01152

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Calyculin: Nature’s way of making the sponge-derived cytotoxin2016

    • Author(s)
      T. Wakimoto, Y. Egami, I. Abe
    • Journal Title

      Nat. Prod. Rep.

      Volume: 未定 Issue: 6 Pages: 751-760

    • DOI

      10.1039/c5np00123d

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] An unusual chimeric diterpene synthase from Emericella varicolor and its functional conversion into a sesterterpene synthase by domain swapping2016

    • Author(s)
      B. Qin, Y. Matsuda, T. Mori, M. Okada, Z. Quan, T. Mitsuhashi, T. Wakimoto, I. Abe
    • Journal Title

      Angew. Chem. Int. Ed.

      Volume: 55 Issue: 5 Pages: 1658-1661

    • DOI

      10.1002/anie.201509263

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Metagenomic analysis of the sponge Discodermia reveals the production of the cyanobacterial natural product kasumigamide by 'Entotheonella'2016

    • Author(s)
      Nakashima, Y., Egami, Y., Kimura, M., Wakimoto, T., Abe, I.
    • Journal Title

      PLoS ONE

      Volume: 11 Issue: 10 Pages: e0164468-e0164468

    • DOI

      10.1371/journal.pone.0164468

    • NAID

      120005893293

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Sulfoureido lipopeptides from the marine sponge Discodermia kiiensis2016

    • Author(s)
      Tan, K. C., Wakimoto, T., Abe, I.
    • Journal Title

      J. Nat. Prod.

      Volume: 79 Issue: 9 Pages: 2418-2422

    • DOI

      10.1021/acs.jnatprod.6b00586

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [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
  • [Journal Article] Concise synthesis of anserine: efficient solvent tuning in asymmetric hydrogenation reaction2016

    • Author(s)
      M. Yamashita, K. Shimizu, Y. Koizumi, T. Wakimotoa, Y. Hamashima, T. Asakawa, M. Inai, T. Kan
    • Journal Title

      Synlet

      Volume: 27 Issue: 19 Pages: 2734-2736

    • DOI

      10.1055/s-0035-1562796

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Syntheses of methylated catechins and theaflavins using the Ns group to protect and deactivate the phenol2016

    • Author(s)
      T. Asakawa, Y. Kawabe, A. Yoshida, Y. Aihara, T. Manabe, Y. Hirose, A. Sakurada, M. Inai, Y. Hamashima, T. Furuta, T. Wakimoto, T. Kan
    • Journal Title

      J. Antibiot.

      Volume: 69 Issue: 4 Pages: 299-312

    • DOI

      10.1038/ja.2016.14

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 海綿共生微生物による生物活性物質の生産2016

    • Author(s)
      江上蓉子, 脇本敏幸, 阿部郁朗
    • Journal Title

      バイオインダストリー

      Volume: 33 Pages: 11-17

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Uncovering the unusual D-ring construction in terretonin biosynthesis by collaboration of a multifunctional cytochrome P450 and a unique isomerase2015

    • Author(s)
      Matsuda, Y., Iwabuchi, T., Wakimoto, T., Awakawa, T., Abe, I.
    • Journal Title

      J. Am. Chem. Soc.

      Volume: 137 Issue: 9 Pages: 3393-3401

    • DOI

      10.1021/jacs.5b00570

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Structural basis for the β-carboline alkaloids production by the microbial homodimeric enzyme McbB2015

    • Author(s)
      T. Mori, S. Hoshino, S. Sahashi, T. Wakimoto, T. Matsui, H. Morita, I. Abe
    • Journal Title

      Chem. Biol.

      Volume: 17 Issue: 7 Pages: 1501-1504

    • DOI

      10.1016/j.chembiol.2015.06.006

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Chojalactones A-C, Cytotoxic Butanolides Isolated from Streptomyces sp. Cultivated with Mycolic Acid Containing Bacterium.2015

    • Author(s)
      Hoshino S, Wakimoto T, Onaka H, Abe I.
    • Journal Title

      Org Lett.

      Volume: 印刷中 Issue: 6 Pages: 1501-1504

    • DOI

      10.1021/acs.orglett.5b00385

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Production of indole antibiotics induced by exogenous gene derived from sponge metagenome2015

    • Author(s)
      Y. Takeshige, Y. Egami, T. Wakimoto, I. Abe
    • Journal Title

      Mol. BioSyst.

      Volume: 11 Issue: 5 Pages: 1290-1294

    • DOI

      10.1039/c5mb00131e

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Dietziamides, novel tetramic acid dimers from Dietzia timorensis MZ-3 with antioxidative activity2015

    • Author(s)
      S. Hoshino, T. Wakimoto, H. Zhang, F. Hayashi, M. Okada, I. Abe
    • Journal Title

      Bioorg. Med. Chem. Lett.

      Volume: 25 Issue: 18 Pages: 3953-3955

    • DOI

      10.1016/j.bmcl.2015.07.035

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Niizalactams A-C, multicyclic macrolactams isolated from combined culture of Streptomyces with mycolic acid-containing bacterium2015

    • Author(s)
      S. Hoshino, M. Okada, T. Wakimoto, H. Zhang, F. Hayashi, H. Onaka, I. Abe
    • Journal Title

      J. Nat. Prod.

      Volume: 78 Issue: 12 Pages: 3011-3017

    • DOI

      10.1021/acs.jnatprod.5b00804

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 海綿動物の化学防御を担う共生細菌2015

    • Author(s)
      江上蓉子、脇本敏幸、阿部郁朗
    • Journal Title

      細胞工学

      Volume: 34 Pages: 412-416

    • NAID

      40020416788

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] Toward the dark matter of marine natural products2017

    • Author(s)
      Toshiyuki Wakimoto
    • Organizer
      International Symposium on Marine Natural Products
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2017-02-28
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A Bacterial Symbiont in Japanese Marine Sponges Produces Biologically Active Metabolites2016

    • Author(s)
      Toshiyuki Wakimoto
    • Organizer
      The 3rd Myanmar-Japan International Symposium
    • Place of Presentation
      Pathein, Myanmar
    • Year and Date
      2016-12-03
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 海綿動物由来生物活性物質の探索と生合成研究2016

    • Author(s)
      脇本敏幸
    • Organizer
      若手研究者のための有機化学札幌セミナー
    • Place of Presentation
      北海道大学理学部(北海道札幌市)
    • Year and Date
      2016-11-29
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Marine sponge-derived metagenomes/uncultured bacteria - a rich source of novel natural product biosynthetic genes2016

    • Author(s)
      Toshiyuki Wakimoto
    • Organizer
      Czech-Japan Joint Workshop
    • Place of Presentation
      Prague, Czech Republic
    • Year and Date
      2016-11-09
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 難培養微生物を起源とする海綿由来生物活性物質の生合成研究2016

    • Author(s)
      脇本敏幸
    • Organizer
      日本農芸化学会2016年度大会
    • Place of Presentation
      札幌コンベンションセンター(北海道札幌市)
    • Year and Date
      2016-03-30
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Recent topics in natural product-derived protein phosphatase inhibitors2016

    • Author(s)
      T. Wakimoto
    • Organizer
      第93回 日本生理学会
    • Place of Presentation
      札幌コンベンションセンター(北海道札幌市)
    • Year and Date
      2016-03-22
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Activated Chemical Defense of a Sponge-Microbe Association2016

    • Author(s)
      T. Wakimoto
    • Organizer
      Gordon Research Conference Marine Natural Products
    • Place of Presentation
      Ventura, CA, USA
    • Year and Date
      2016-03-08
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] A Bacterial Symbiont in Japanese Marine Sponges Produces Biologically Active Metabolites2016

    • Author(s)
      T. Wakimoto
    • Organizer
      The 4th Frontier Chemistry Center International Symposium
    • Place of Presentation
      北海道大学(北海道札幌市)
    • Year and Date
      2016-02-23
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 海綿―共生微生物系の化学防御機構2015

    • Author(s)
      脇本敏幸
    • Organizer
      第67回 日本生物工学会
    • Place of Presentation
      城山観光ホテル(鹿児島県鹿児島)
    • Year and Date
      2015-10-27
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 海洋天然物化学が明示した難培養微生物の存在2015

    • Author(s)
      脇本敏幸
    • Organizer
      第50回 天然物化学談話会
    • Place of Presentation
      グリーンピア岩沼(宮城県岩沼市)
    • Year and Date
      2015-07-03
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 海綿―共生微生物系の化学防御機構2015

    • Author(s)
      脇本敏幸
    • Organizer
      第10回 化学生態学研究会
    • Place of Presentation
      湯の川プリンスホテル渚亭(北海道函館市)
    • Year and Date
      2015-06-13
    • Related Report
      2015 Research-status Report
    • Invited
  • [Book] 「天然物の化学ー魅力と展望ー」上村大輔編, 科学のとびら602016

    • Author(s)
      脇本敏幸
    • Publisher
      東京化学同人
    • Related Report
      2016 Annual Research Report
  • [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

    • Related Report
      2016 Annual Research Report 2015 Research-status Report

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Published: 2015-04-16   Modified: 2018-03-22  

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