Reprogramming of the polyketide synthase/peptide synthetase from Streptomyces

• Project/Area Number: 16K13084
• 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: Abe Ikuro 東京大学, 大学院薬学系研究科(薬学部), 教授 (40305496)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 合成生物学 / 生合成 / 天然物化学 / 酵素工学 / 構造生物学 / アンチマイシン

Outline of Final Research Achievements

Reprogramming of the NRPS/PKS assembly line is an attractive method for the creation of novel bioactive molecules. In this study, we successfully accomplished three manipulations: i) ring contraction, ii) ring expansion, and iii) alkyl chain diversification, to generate a set of unnatural novel derivatives in practical yields. This study presented a useful strategy for engineering NRPS-PKS module enzymes.

Research Products

• [Int'l Joint Research] 上海有機化学研究所(中国)
• [Journal Article] Characterization of giant modular PKSs provides insight into genetic mechanism for structural diversification of aminopolyol polyketides (2017)
  • 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
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Unusual Enzyme Reactions in Fungal Meroterpenoid Biosynthesis (2018)
  • Author(s): Ikuro Abe
  • Organizer: The Society for Industrial Microbiology (SIMB), “2nd International Conference on Natural Product Discovery and Development in the Genomic Era”
  • 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）
  • 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] 放線菌由来生物活性二次代謝産物の生合成研究 (2017)
  • Author(s): 阿部郁朗
  • Organizer: 公益財団法人日本感染症医薬品協会、メディカルサイエンス・セミナー、住木・梅澤記念賞受賞講演
  • Invited
• [Presentation] Engineered Biosynthesis of Medicinal Natural Product (2017)
  • Author(s): Ikuro Abe
  • Organizer: The American Society of Pharmacognosy Annual Meeting
  • Int'l Joint Research / Invited
• [Presentation] Enzymes Involved in the Complex Natural Products Biosynthesis (2017)
  • Author(s): Ikuro Abe
  • Organizer: 9th US-Japan Seminar on Natural Product Biosynthesis
  • Int'l Joint Research / 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: 2016-11-09
  • 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
• [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