Development and applications of biomimetic peptide synthesis

• Project/Area Number: 18K14396
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 38040:Bioorganic chemistry-related
• Research Institution: Kyoto University
• Principal Investigator: Kuranaga Takefumi 京都大学, 薬学研究科, 助教 (70625201)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: ペプチド / 生合成 / 有機合成 / 全合成 / 天然物化学

Outline of Final Research Achievements

In this project, the development of a new methodology for the biomimetic peptide synthesis and its applications to the biosynthetic studies on the structurally unique peptidic natural products were achieved. The new methodology has been efficiently utilized in the biosynthetic studies on the peptidic natural products, namely, cyclic peptides surugamides A-E, a linear peptide surugamide F, and a hybrid peptide-polyketide natural product kasumigamide.
In addition to this, the complete structural determination of the new peptiditic natural products,thioamycolamides A-E, were also accomplished by the chemical syntheses program in this project.

Academic Significance and Societal Importance of the Research Achievements

本研究は学術界・産業界いずれでも当然のように文字通り「不自然」な向きにペプチド鎖が伸長されている現在の化学合成を一新しうる重大な意義を持つ研究である。また現代における未知の生合成酵素メカニズム解明は、遺伝子操作や配列相同性検索などから芋づる式に未知の天然物の発見を導く。そのため本研究は化学合成を足がかりとした生合成メカニズム解明研究から、新規有用生物活性化合物(新規創薬リード)探索研究としての展開・社会への貢献が期待される研究でもある。

Research Products

• [Journal Article] Thioamycolamides A-E, Sulfur-Containing Cycliclipopeptides Produced by the Rare Actinomycete Amycolatopsis sp. (2020)
  • Author(s): Chengqian Pan, Takefumi Kuranaga, Chao Liu, Shan Lu, Naoya Shinzato, Hideaki Kakeya
  • Journal Title: Org. Lett. Volume: 22 Issue: 8 Pages: 3014-3017
  • DOI: 10.1021/acs.orglett.0c00776
  • Peer Reviewed
• [Journal Article] A New Cyclase Family Catalyzing Head-to-Tail Macrolactamization of Non-ribosomal Peptides (2019)
  • Author(s): Matsuda Kenichi、Kuranaga Takefumi、Wakimoto Toshiyuki
  • Journal Title: Journal of Synthetic Organic Chemistry, Japan Volume: 77 Issue: 11 Pages: 1106-1115
  • DOI: 10.5059/yukigoseikyokaishi.77.1106
  • NAID: 130007742538
  • ISSN: 0037-9980, 1883-6526
  • Year and Date: 2019-11-01
  • Peer Reviewed
• [Journal Article] The Revised Structure of the Cyclic Octapeptide Surugamide A (2019)
  • 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
  • Peer Reviewed
• [Journal Article] ペニシリン結合タンパク質によるペプチド環化 (2019)
  • Author(s): 松田 研一、倉永 健史、脇本 敏幸
  • Journal Title: Farumashia Volume: 55 Issue: 7 Pages: 650-654
  • DOI: 10.14894/faruawpsj.55.7_650
  • NAID: 130007671605
  • ISSN: 0014-8601, 2189-7026
  • Peer Reviewed
• [Journal Article] Scrobiculosides A and B from the deep-sea sponge Pachastrella scrobiculosa (2019)
  • Author(s): Jomori Takahiro、Ise Yuji、Kohtsuka Hisanori、Matsuda Kenichi、Kuranaga Takefumi、Wakimoto Toshiyuki
  • Journal Title: Journal of Natural Medicine Volume: 73 Issue: 4 Pages: 1058-1061
  • DOI: 10.1007/s11418-019-01315-6
  • NAID: 40021995195
  • Peer Reviewed
• [Journal Article] Introduction of D-Amino Acids in Minimalistic Peptide Substrates by an S-Adenosyl-L-Methionine Radical Epimerase (2019)
  • Author(s): Anna L. Vagstad, Takefumi Kuranaga, Salome Puentener, Vijay Pattabiraman, Jeffrey W. Bode, Joern Piel
  • Journal Title: Angew. Chem. Int. Ed. Volume: 58 Issue: 8 Pages: 2246-2250
  • DOI: 10.1002/anie.201809508
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] SurE is a trans-acting thioesterase cyclizing two distinct non-ribosomal peptides (2019)
  • Author(s): Matsuda, K., Kobayashi, M., Kuranaga, T., Takagda, K., Ikeda, H., Matsunaga, S., Wakimoto, T.,
  • Journal Title: Org. Biomol. Chem. Volume: 17 Issue: 5 Pages: 1058-1061
  • DOI: 10.1039/c8ob02867b
  • Peer Reviewed / Open Access
• [Journal Article] Total Synthesis of the Nonribosomal Peptide Surugamide?B and Identification of a New Offloading Cyclase Family (2018)
  • Author(s): Kuranaga Takefumi、Matsuda Kenichi、Sano Ayae、Kobayashi Masakazu、Ninomiya Akihiro、Takada Kentaro、Matsunaga Shigeki、Wakimoto Toshiyuki
  • Journal Title: Angewandte Chemie International Edition Volume: 57 Issue: 30 Pages: 9447-9451
  • DOI: 10.1002/anie.201805541
  • Peer Reviewed
• [Presentation] 実用的inverseペプチド合成法の開発 (2020)
  • Author(s): 森本涼太, 倉永健史, 脇本敏幸, 掛谷秀昭
  • Organizer: 日本薬学会第140年会
• [Presentation] Chemical Synthesis and Biosynthesis of Peptidic Natural Products (2020)
  • Author(s): Takefumi Kuranaga
  • Organizer: 日本化学会第100春季年会「若い世代の特別講演」
  • Invited
• [Presentation] 田地川千里1, 松田研一2, 倉永健史3,脇本敏幸2 (2019)
  • Author(s): スルガミド環化酵素SurEによる環状カスミガミドの合成
  • Organizer: 第８回食品薬学シンポジウム
• [Presentation] ものとり指向型化学合成 (2019)
  • Author(s): 倉永健史
  • Organizer: 第54回天然物化学談話会（受賞講演）
  • Invited
• [Presentation] Chemical Synthesis and Biosynthesis of Scarce Natural Products (2018)
  • Author(s): Takefumi Kuranaga
  • Organizer: International Congress on Pure & Applied Chemistry Langkawi (ICPAC Langkawi)
  • Int'l Joint Research / Invited