Discovery of novel peptide natural product with anti bacterial activities

• Project/Area Number: 18K19388
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 47:Pharmaceutical sciences and related fields
• Research Institution: Tohoku University (2019-2020); The University of Tokyo (2018)
• Principal Investigator: Teigo Asai 東北大学, 薬学研究科, 教授 (60572310)
• Project Period (FY): 2018-06-29 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 天然物化学 / 抗生物質 / ペプチド天然物 / 生合成 / 異種発現 / ゲノムマインング / 天然物 / 糸状菌 / ゲノムマイニング / 活性天然物 / 非リボソーム型ペプチド合成酵素 / ペプチド / 二次代謝物 / 麹菌

Outline of Final Research Achievements

Peptide natural products are promising source for antibiotics. Therefore, discovery of novel natural peptide natural products is important for drug development. In this research, we aimed to discover novel peptide natural products based on genome mining and heterologous expression of Aspergillus oryzae. Genome mining enabled us to find a biosynthetic gene cluster that may code novel natural depsipeptide in a Chaetomium fungi. Reconstruction of the cluster in Aspergillu oryzae gave us a novel depsipeptide as expected. The structure of the depsipeptide was fully determined by spectral analyses and chemical conversion approach.

Academic Significance and Societal Importance of the Research Achievements

本研究は、糸状菌のゲノム情報から合理的に新しいペプチド天然物を獲得する方法を提示し、実際に、新規デプシペプチドの獲得に成功した。ペプチド天然物は抗生物質の重要な探索源であり、本研究成果は、新しい抗生物質の開発に貢献することが期待される。様々な生物のゲノム上には、膨大な数のペプチド天然物が眠っている。本研究を拡大することで、今後数多くの抗生物質シーズを開拓できることが期待される。

Research Products

• [Journal Article] Synthetic biology based construction of biological activity-related library focused on fungal decalin-containing diterpenoid pyrones (2020)
  • Author(s): 1.Tsukada K, Shinki S, Kaneko A, Murakami K, Irie K, Murai M, Miyoshi H, Dan S, Kawaji K, Hayashi H, Kodama E, Hori A, Salim E, Kuraishi T, Hirata N, Kanda Y, Asai T.
  • Journal Title: Nature Communications Volume: 11 Issue: 1 Pages: 1830-1830
  • DOI: 10.1038/s41467-020-15664-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genome Mining-Based Discovery of Fungal Macrolides Modified by glycosylphosphatidylinositol (GPI)?Ethanolamine Phosphate Transferase Homologues (2020)
  • Author(s): Morishita Yohei、Aoki Yu、Ito Mei、Hagiwara Daisuke、Torimaru Kensho、Morita Daichi、Kuroda Teruo、Fukano Hanako、Hoshino Yoshihiko、Suzuki Masato、Taniguchi Tohru、Mori Keiji、Asai Teigo
  • Journal Title: Organic Letters Volume: 22 Issue: 15 Pages: 5876-5879
  • DOI: 10.1021/acs.orglett.0c01975
  • Peer Reviewed / Open Access
• [Presentation] Chaetomium属菌のゲノム上にコードされた新規デプシペプチドの獲得 (2021)
  • Author(s): 本間悠人、森下陽平、塚田健人、浅井禎吾
  • Organizer: 日本薬学会第141年会
• [Presentation] Post-genomic discovery of fungal natural products based on genome mining and heterologous expression (2020)
  • Author(s): Teigo Asai
  • Organizer: Cutting-edge natural product chemistry -next generation biomolecule redesign-
• [Presentation] 糸状菌ゲノム情報を活用するポストゲノム型天然物探索研究 (2019)
  • Author(s): 浅井禎吾
  • Organizer: 第102回日本細菌学会関東支部総会
• [Presentation] 糸状菌ゲノム情報に基づくポストゲノム型天然物探索研究 (2019)
  • Author(s): 浅井禎吾
  • Organizer: 第 66 回日本放線菌学会学術講演会
• [Presentation] 新たな医薬資源を開拓する糸状菌ポストゲノム型天然物探索研究 (2019)
  • Author(s): 浅井禎吾
  • Organizer: 第139回日本薬学会年会シンポジウム
  • Invited
• [Presentation] 麹菌異種発現を基盤とする天然物探索研究 (2018)
  • Author(s): 浅井禎吾
  • Organizer: 糸状菌相互応答学セミナー
  • Invited
• [Presentation] Discovery of natural products based on re-construction and re-designing of fungal cryptic biosynthetic gene clusters in Aspergillus oryzae (2018)
  • Author(s): Teigo Asai
  • Organizer: Japanese-German Symposium
  • Int'l Joint Research / Invited