Collection and survey of biosynthetic genes of spore-derived biologically active substances and clarification of biosynthetic machinery

• Project/Area Number: 26303005
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 海外学術
• Research Field: Biomolecular chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: Abe Ikuro 東京大学, 大学院薬学系研究科(薬学部), 教授 (40305496)
• Co-Investigator(Kenkyū-buntansha): 脇本 敏幸 北海道大学, 薬学研究院, 教授 (70363900)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000); Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2016: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2015: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
• Keywords: 海洋天然物 / 生合成遺伝子 / 海綿動物 / 共生菌 / 採集調査 / 海洋天然薬物

Outline of Final Research Achievements

By collecting sponges in the Pacific region and isolating and comparing biosynthesis genes, we elucidated its biosynthetic machinery and searched for origin of structural diversity of natural products. At the same time, we investigated the possibility of producing bacteria common to these sponges and investigated the universality of the distribution of symbiotic bacteria excelling in substance production. As a result, the importance of marine biological resources in the Pacific region was demonstrated, and great contribution was expected to future drug development.

Research Products

• [Int'l Joint Research] ヤンゴン大学(ミャンマー)
• [Int'l Joint Research] ＬＩＰＩ/バンドン工科大学(インドネシア)
• [Int'l Joint Research] マレーシア大学ＵＫＭ(マレーシア)
• [Int'l Joint Research] Jinan大学/北京医薬大(中国)
• [Int'l Joint Research] フリンダース大学(オーストラリア)
• [Int'l Joint Research]
• [Int'l Joint Research] The Indonesian Institute of Sciences(インドネシア)
• [Int'l Joint Research] フリンダース大学(オーストラリア)
• [Int'l Joint Research] フエ医科薬科大学(ベトナム)
• [Int'l Joint Research] ヤンゴン大学(ミャンマー)
• [Journal Article] Two new pyrrolo-2-aminoimidazoles, Clathriroles A and B, from marine sponge, Clathria prolifera collected in Myanmar (2018)
  • Author(s): Woo, S.-Y., Win, N. N., Wong, C. P., Ito, T., Hoshino, S., Ngwe, H., Aye, A. A., Han, N., Zhang, H., Hayashi, F., Abe, I., Morita, H.
  • Journal Title: J. Nat. Med., Volume: 72 Issue: 3 Pages: 803-807
  • DOI: 10.1007/s11418-018-1205-y
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Umezawamides, new bioactive polycyclic tetramate macrolactams isolated from a combined-culture of Umezawaea sp. and mycolic acid-containing bacterium (2018)
  • Author(s): Hoshino Shotaro、Wong Chin Piow、Ozeki Masahiro、Zhang Huiping、Hayashi Fumiaki、Awakawa Takayoshi、Asamizu Shumpei、Onaka Hiroyasu、Abe Ikuro
  • Journal Title: The Journal of Antibiotics Volume: 71 Issue: 7 Pages: 653-657
  • DOI: 10.1038/s41429-018-0040-4
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Tetrahydrofuran lignans: Melanogenesis inhibitors from Premna integrifolia wood collected in Myanmar (2018)
  • Author(s): Win Nwet Nwet、Woo So-Yeun、Ngwe Hla、Prema、Wong Chin Piow、Ito Takuya、Okamoto Yasuko、Tanaka Masami、Imagawa Hiroshi、Asakawa Yoshinori、Abe Ikuro、Morita Hiroyuki
  • Journal Title: Fitoterapia Volume: 123 Pages: 308-313
  • DOI: 10.1016/j.fitote.2018.03.002
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Identification of pyridinium with three indole moieties as an antimicrobial agent (2017)
  • 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
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Total synthesis of theonellapeptolide Id (2017)
  • 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
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 3,5-Dimethylorsellinic Acid Derived Meroterpenoids from Penicillium chrysogenum MT-12, an Endophytic Fungus Isolated from Huperzia serrata (2017)
  • Author(s): Qi Bowen、Liu Xiao、Mo Ting、Zhu Zhixiang、Li Jun、Wang Juan、Shi Xiaoping、Zeng Kewu、Wang Xiaohui、Tu Pengfei、Abe Ikuro、Shi Shepo
  • Journal Title: Journal of Natural Products Volume: 80 Issue: 10 Pages: 2699-2707
  • DOI: 10.1021/acs.jnatprod.7b00438
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Labdane diterpenoids from Curcuma amada rhizomes collected in Myanmar and their antiproliferative activities (2017)
  • Author(s): Win Nwet Nwet、Ito Takuya、Ngwe Hla、Win Yi Yi、Prema、Okamoto Yasuko、Tanaka Masami、Asakawa Yoshinori、Abe Ikuro、Morita Hiroyuki
  • Journal Title: Fitoterapia Volume: 122 Pages: 34-39
  • DOI: 10.1016/j.fitote.2017.08.006
  • Peer Reviewed / Int'l Joint Research
• [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
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Calyculin: Nature’s way of making the sponge-derived cytotoxin (2016)
  • 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
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Sulfoureido lipopeptides from the marine sponge Discodermia kiiensis (2016)
  • 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
  • Peer Reviewed / Acknowledgement Compliant
• [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
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Production of indole antibiotics induced by exogenous gene derived from sponge metagenome (2015)
  • 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
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 海綿–共生微生物系の化学防御機構 (2015)
  • Author(s): 脇本敏幸, 江上蓉子, 阿部郁朗
  • Journal Title: KAGAKU TO SEIBUTSU Volume: 53 Issue: 8 Pages: 497-499
  • DOI: 10.1271/kagakutoseibutsu.53.497
  • NAID: 130005165653
  • ISSN: 0453-073X, 1883-6852
  • 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
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] カイメンー共生バクテリア系の化学防御機 (2015)
  • Author(s): 脇本敏幸, 阿部郁朗
  • Journal Title: バイオサイエンスとインダストリー Volume: 34 Pages: 49-51
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] カイメンー共生バクテリア系の化学防御機構 (2015)
  • Author(s): 脇本敏幸, 阿部郁朗
  • Journal Title: バイオサイエンスとインダストリー Volume: 73 Pages: 49-51
• [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] 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] 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] 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] 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
• [Presentation] Engineered Biosynthesis of Medicinal Natural Products (2018)
  • Author(s): Ikuro Abe
  • Organizer: 34th International Conference on Natural Products 2018 (ICNP 2018)
  • Int'l Joint Research / Invited
• [Presentation] Engineered Biosynthesis of Medicinal Natural Products (2018)
  • Author(s): Ikuro Abe
  • Organizer: 8th CMDD Symposium on Marine Natural Products
  • Int'l Joint Research / Invited
• [Presentation] Redesigning Complex Natural Products Biosynthesis (2017)
  • Author(s): 阿部郁朗
  • Organizer: PSJ-AAPS Joint Symposium, Creation of Complex Functional Molecules by Rational Redesign of Biosynthetic Machineries
  • Place of Presentation: 仙台国際センター（宮城県・仙台市）
  • Year and Date: 2017-03-26
  • Int'l Joint Research / Invited
• [Presentation] 複雑骨格天然物の生合成マシナリーの解明と再設計 (2017)
  • Author(s): 阿部郁朗
  • Organizer: 日本農芸化学会2017年度京都大会シンポジウム、農芸化学から発信する次世代型天然物化学
  • Place of Presentation: 京都女子大（京都府・京都市）
  • Year and Date: 2017-03-18
  • Invited
• [Presentation] Engineered Biosynthesis of Medicinal Natural Products (2017)
  • Author(s): 阿部郁朗
  • Organizer: The 2nd International Conference on Herbal and Traditional Medicine (HTM2017)
  • Place of Presentation: Bangkok (Thailand)
  • Year and Date: 2017-01-25
  • Int'l Joint Research / Invited
• [Presentation] 薬用天然物の生合成リデザイン (2017)
  • Author(s): 阿部郁朗
  • Organizer: 理研シンポジウム、高磁場・高感度NMR利活用促進のための天然物分野における日中連携シンポジウム2017
  • Int'l Joint Research / Invited
• [Presentation] 薬用天然物の生合成工学に関する研究 (2017)
  • Author(s): 阿部郁朗
  • Organizer: 日本生薬学会 第64回年会、生薬学会賞受賞講演
  • Invited
• [Presentation] Marine sponge-derived metagenomes/uncultured bacteria - a rich source of novel natural product biosynthetic genes (2017)
  • Author(s): Toshiyuki Wakimoto
  • Organizer: International Conference on Marine Biodiversity and Biotechnology (Jakarta, Indonesia)
  • Int'l Joint Research / Invited
• [Presentation] Activated Chemical Defense of Japanese Marine Sponge Discodermia calyx (2017)
  • Author(s): Toshiyuki Wakimoto
  • Organizer: 2017 ISCE/APACE (Kyoto, Japan)
  • Int'l Joint Research / Invited
• [Presentation] Activated Chemical Defense of a Sponge-microbe Association (2017)
  • Author(s): Toshiyuki Wakimoto
  • Organizer: University of Yangon (Yangon, Myanmar)
  • Invited
• [Presentation] メタゲノムマイニングによる海綿由来新規天然物の探索 (2017)
  • Author(s): 脇本敏幸
  • Organizer: 理研シンポジウム、高磁場・高感度NMR利活用促進のための天然物分野における 日中連携シンポジウム2017
  • Invited
• [Presentation] Engineered Biosynthesis of Medicinal Natural Products (2016)
  • Author(s): 阿部郁朗
  • Organizer: 2016 Mogan Mountain International Summit on Green Pharmaceuticals
  • Place of Presentation: Hangzhou (China)
  • Year and Date: 2016-11-02
  • Int'l Joint Research / Invited
• [Presentation] Multifunctional Oxygenases Involved in Complex Natural Products Biosynthesis (2016)
  • Author(s): 阿部郁朗
  • Organizer: Cytochrome P450 Biodiversity & Biotechnology 2016
  • Place of Presentation: Vancouver (Canada)
  • Year and Date: 2016-07-26
  • Int'l Joint Research / Invited
• [Presentation] Activated Chemical Defense of a Sponge-Microbe Association (2016)
  • Author(s): Toshiyuki Wakimoto
  • Organizer: Gordon Research Conference, Marine Natural Products
  • Place of Presentation: Ventura, USA
  • Year and Date: 2016-03-06
  • Int'l Joint Research / Invited
• [Presentation] Activated Chemical Defense of a Sponge-Microbe Association (2015)
  • Author(s): Toshiyuki Wakimoto
  • Organizer: PACIFICHEM2015
  • Place of Presentation: Hawaii, USA
  • Year and Date: 2015-12-15
  • Int'l Joint Research / Invited
• [Presentation] Engineered Biosynthesis of Medicinal Natural Products (2015)
  • Author(s): 阿部郁朗
  • Organizer: International Conference on Natural Products 2015
  • Place of Presentation: Johor Bahru, Malaysia
  • Year and Date: 2015-03-24 – 2015-03-25
  • Invited
• [Presentation] Calyculin Biogenesis from a Pyrophosphate Protoxin Produced by a Sponge Symbiont (2014)
  • Author(s): 阿部郁朗
  • Organizer: Flinders University Lecture Series
  • Place of Presentation: Flinders Univ, Australia
  • Year and Date: 2014-11-24 – 2014-11-27
  • Invited
• [Presentation] Calyculin Biogenesis from a Pyrophosphate Protoxin Produced by a Sponge Symbiont (2014)
  • Author(s): 阿部郁朗
  • Organizer: International Symposium on Marine Biotechnology and Ocean Conservation
  • Place of Presentation: Surya Univ, Indonesia
  • Year and Date: 2014-09-15 – 2014-09-16
  • Invited
• [Presentation] Engineered Biosynthesis of Medicinal Natural Products (2014)
  • Author(s): 阿部郁朗
  • Organizer: 9th International Symposium on Chromatography of Natural Product
  • Place of Presentation: Lubrin, Poland
  • Year and Date: 2014-05-26 – 2014-05-29
  • Invited
• [Remarks] 東京大学大学院薬学系研究科天然物化学教室
  • URL: http://www.f.u-tokyo.ac.jp/~tennen/head.htm
• [Remarks] 東京大学大学院薬学系研究科天然物化学教室ホームページ
  • URL: http://www.f.u-tokyo.ac.jp/~tennen/head.htm
• [Remarks] 東京大学大学院薬学系研究科天然物化学教室ホームページ
  • URL: http://www.f.u-tokyo.ac.jp/~tennen/publications.html