Identification and genome analysis of bacterial symbiont producing sponge-derived secondary metabolites

• Project/Area Number: 25560399
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biomolecular chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: WAKIMOTO Toshiyuki 東京大学, 薬学研究科(研究院), 准教授 (70363900)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 海綿共生微生物 / 生物活性物質 / Discodermia / Theonella / 生合成

Outline of Final Research Achievements

In this study, we tried to identify the bacterial symbiont producing sponge-derived secondary metabolites. Theonellidae family sponges are well known to contain diverse secondary metabolites. However, the real producer of them had been unknown, though it had been supposed to be symbiont bacteria. The identification of such bacteria could be a key issue to pave the way for the supply limitation of medicinally important sponge-derived compounds. Three Theonellidae sponge species were therefore subjected to genetic evaluation, cell separation and single cell analysis. As a result, the Entotheonella was identified to be the real producer of almost all secondary metabolites of three sponge spieces. Our findings provide not only the proof of a sponge-specific molecule synthesized by the unique and uncultured bacterium rather than sponge itself, but also useful insights into the supply of sponge-derived medicinally important compounds.

Research Products

• [Journal Article] Calyculin biogenesis from a pyrophosphate protoxin produced by a sponge symbiont (2014)
  • Author(s): Wakimoto, T., Egami, Y., Nakashima, Y., Wakimoto,Y., Mori, T., Awakawa,T., Ito, T., Kenmoku, H., Asakawa, Y., Piel, J., Abe, I.
  • Journal Title: Nature Chem. Biol. Volume: 10 Issue: 8 Pages: 648-655
  • DOI: 10.1038/nchembio.1573
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Complete biosynthetic pathway of anditomin: nature's sophisticated synthetic route to a complex fungal meroterpenoid (2014)
  • Author(s): Matsuda, Y., Wakimoto, T., Mori, T., Awakawa, T., Abe, I.
  • Journal Title: J. Am. Chem. Soc. Volume: 136 Issue: 43 Pages: 15326-15336
  • DOI: 10.1021/ja508127q
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A methyltransferase initiates terpene cyclization in teleocidin B biosynthesis (2014)
  • Author(s): Awakawa, T., Zhang, L., Wakimoto, T., Hoshino, S., Mori, T., Ito, T., Ishikawa, J., Tanner, M. E., Abe, I.
  • Journal Title: J. Am. Chem. Soc. Volume: 136 Issue: 28 Pages: 9910-9913
  • DOI: 10.1021/ja505224r
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Phosphocalyculin C as a pyrophosphate protoxin of calyculin C in the marine sponge Discodermia calyx (2014)
  • Author(s): Y. Egami, T. Wakimoto, I. Abe
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 24 Issue: 22 Pages: 5150-5153
  • DOI: 10.1016/j.bmcl.2014.10.002
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Arcyriaflavin E, a new cytotoxic indolocarbazole alkaloid isolated by combined-culture of mycolic acid-containing bacteria and Streptomyces cinnamoneus NBRC 13823. (2014)
  • Author(s): S. Hoshino, L. Zhang, T. Awakawa, T. Wakimoto, H. Onaka, I. Abe
  • Journal Title: J. Antibiot. Volume: 67 Issue: 5 Pages: 1-3
  • DOI: 10.1038/ja.2014.147
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Three acyltetronic acid derivatives: noncanonical cryptic polyketides from Aspergillus niger identified by genome mining (2014)
  • Author(s): Yang, X.-L., Awakawa, T., Wakimoto, T., Abe, I.
  • Journal Title: ChemBioChem Volume: 15 Issue: 11 Pages: 1578-1583
  • DOI: 10.1002/cbic.201402172
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Lipodiscamides A-C, new cytotoxic lipopeptides from the marine sponge Discodermia kiiensis (2014)
  • Author(s): K. C. Tan, T. Wakimoto, I. Abe
  • Journal Title: Org. Lett. Volume: 16 Issue: 12 Pages: 3256-3259
  • DOI: 10.1021/ol501271v
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] An environmental bacterial taxon with a large and distinct metabolic repertoire (2014)
  • Author(s): Wilson, M. C., Mori, T., Ruckert, C., Uria, A. R., Helf, M. J., Takada, K., Gernert, C., Steffens, U. A. E., Heycke, N., Schmitt, S., Rinke, C., Helfrich, E. J. N., Brachmann, A. O., Gurgui, C., Wakimoto. T., Kracht, M., Crusemann, M., Hentschel, U., Abe, I., Matsunaga, S., Kalinowski, J., Takeyama, H., Piel, J.
  • Journal Title: Nature Volume: 506 Issue: 7486 Pages: 58-62
  • DOI: 10.1038/nature12959
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Revised structure of cyclolithistide A, a cyclic depsipeptide from the marine sponge Discodermia japonica (2014)
  • Author(s): H. Tajima, T. Wakimoto, K. Takada, Y. Ise, I. Abe
  • Journal Title: J. Nat. Prod. Volume: 77 Issue: 1 Pages: 154-158
  • DOI: 10.1021/np400668k
  • Peer Reviewed
• [Journal Article] Enantioselective Synthesis of SB-203207 (2014)
  • Author(s): Yasuo Hirooka, Kazutada Ikeuchi, Yuichiro Kawamoto, Yusuke Akao, Takumi Furuta, Tomohiro Asakawa, Makoto Inai, Toshiyuki Wakimoto, Tohru Fukuyama and Toshiyuki Kan
  • Journal Title: Org. Lett. Volume: 16 Issue: 6 Pages: 1646-1646
  • DOI: 10.1021/ol5002973
  • Peer Reviewed
• [Journal Article] Spiro-ring formation is catalyzed by a multifunctional dioxygenase in austinol biosynthesis (2013)
  • Author(s): Y. Matsuda, T. Awakawa, T. Wakimoto, and I. Abe
  • Journal Title: J. Am. Chem. Soc. Volume: 135 Issue: 30 Pages: 10962-10965
  • DOI: 10.1021/ja405518u
  • Peer Reviewed
• [Journal Article] Pyranonigrin E : a novel PKS-NRPS hybrid metabolite from Aspergillus niger ide ntified by genome mining (2013)
  • Author(s): Takayoshi Awakawa., Xiao-Long Xia o-Long Yang, Toshiyuki Wakimoto., Ikuro Abe
  • Journal Title: Chembiochem Volume: 14 Issue: 16 Pages: 2095-2099
  • DOI: 10.1002/cbic.201300430
  • Peer Reviewed
• [Journal Article] Cycloforskamide, a cytotoxic macrocyclic peptide from the sea slug Pleurobranchus forskalii (2013)
  • Author(s): K. C. Tan, T. Wakimoto, K. Takada, T. Ohtsuki, N. Uchiyama, Y. Goda, I. Abe
  • Journal Title: J. Nat. Prod. Volume: 76 Issue: 7 Pages: 1388-1391
  • DOI: 10.1021/np400404r
  • Peer Reviewed
• [Journal Article] Cycloforskamide, a cytotoxic macrocyclic peptide from the sea slug Pleurobranchus forskalii (2013)
  • Author(s): K. C. Tan, T. Wakimoto, K. Takada, T. Ohtsuki, N. Uchiyama, Y. Goda, I. Abe
  • Journal Title: Toxicon Volume: 72 Pages: 1-4
  • DOI: 10.1016/j.toxicon.2013.05.021
  • Peer Reviewed
• [Journal Article] Indole-porphyrin hybrids produced by metagenomics (2013)
  • Author(s): Yang, X. -L., Wakimoto, T., Takeshige, Y., He, R., Egami, Y., Abe, I.
  • Journal Title: Bioorganic & Medicinal Chemistry Letters Volume: 23 Issue: 13 Pages: 2810-2813
  • DOI: 10.1016/j.bmcl.2013.04.076
  • Peer Reviewed
• [Journal Article] Induced production of novel prenyldepside and coumarins in endophytic fungi Pestalotiopsis acaciae (2013)
  • Author(s): X.-L. Yang, T. Awakawa, T. Wakimoto, I. Abe
  • Journal Title: Tetrahedron Lett. Volume: 54 Pages: 5814-5817
  • Peer Reviewed
• [Journal Article] Induced production of the novel glycolipid ustilagic acid C in the plant pathogen Ustilago maydis (2013)
  • Author(s): X.-L. Yang, T. Awakawa, T. Wakimoto, I. Abe
  • Journal Title: Tetrahedron Lett. Volume: 54 Pages: 3655-3657
  • Peer Reviewed
• [Journal Article] Induced biosyntheses of a novel butyrophenone and two aromatic polyketides in the plant pathogen Stagonospora nodorum (2013)
  • Author(s): X.-L. Yang, T. Awakawa, T. Wakimoto, I. Abe
  • Journal Title: Nat. Prod. Bioprospect. Volume: 3 Pages: 141-144
  • Peer Reviewed
• [Journal Article] Epigenetic modifier-induced biosynthesis of novel fusaric acid derivatives in endophytic fungi from Datura stramonium L. (2013)
  • Author(s): H.-J. Chen, T. Awakawa, J.-Y. Sun, T. Wakimoto, I. Abe
  • Journal Title: Nat. Prod. Bioprospect. Volume: 3 Pages: 20-23
  • Peer Reviewed
• [Presentation] The significance of unstable marine natural products (2015)
  • Author(s): Toshiyuki Wakimoto
  • Organizer: Marine Biotechnology Seminar
  • Place of Presentation: Adelaide, Australia
  • Year and Date: 2015-02-09
  • Invited
• [Presentation] 海綿由来生物活性物質の生合成に関する研究 (2014)
  • Author(s): 脇本敏幸
  • Organizer: 日本生薬学会第61年会
  • Place of Presentation: 福岡県福岡市
  • Year and Date: 2014-09-14
  • Invited
• [Presentation] 多様な天然物を生産する海綿共生バクテリア (2014)
  • Author(s): 脇本敏幸
  • Organizer: 静岡大学農学部公開講演会
  • Place of Presentation: 静岡県静岡市
  • Year and Date: 2014-07-14
  • Invited
• [Presentation] A bacterial symbiont of Japanese marine sponge Discodermia calyx, produces biologically active metabolites (2013)
  • Author(s): T. Wakimoto, Y. Egami, Y. Nakashima, I. Abe
  • Organizer: 9th World Sponge Conference
  • Place of Presentation: Perth, Australia
  • Invited
• [Presentation] A bacterial symbiont of Japanese marine sponge Discodermia calyx, produces biologically active metabolites (2013)
  • Author(s): T. Wakimoto, Y. Egami, Y. Nakashima, I. Abe
  • Organizer: The 14th International Symposium of Marine Natural Products
  • Place of Presentation: La Toja, Spain
  • Invited
• [Presentation] 海洋生物に由来する医薬品資源の開拓と利用を目指して
  • Author(s): 脇本敏幸
  • Organizer: 第34回和漢医薬学総合研究所 特別セミナー
  • Place of Presentation: 富山県富山市
  • Invited
• [Presentation] 海洋生物に由来する医薬品資源の開拓と利用を目指して
  • Author(s): 脇本敏幸
  • Organizer: 福井県立大学 生物資源学特別セミナー
  • Place of Presentation: 福井県福井市
  • Invited
• [Presentation] 海綿共生微生物を起源とする生理活性物質の生産機構解析
  • Author(s): 脇本敏幸
  • Organizer: 第1回薬学の有機化学を考えるin北海道
  • Place of Presentation: 北海道札幌市
  • Invited
• [Book] Handbook of Anticancer Drug from Marine Origin (2014)
  • Author(s): T. Wakimoto, K. C. Tan, H. Tajima, I. Abe
  • Total Pages: 800
  • Publisher: Springer
• [Remarks] カイメンを気づかう共生バクテリア ―チョコガタイシカイメンの毒性物質はバクテリアが生産していた―
  • URL: http://www.u-tokyo.ac.jp/public/public01_260630_02_j.html
• [Remarks] 海綿動物の化学防御を担う共生細菌
  • URL: http://first.lifesciencedb.jp/archives/9108