Identification of new natural products targeting cell membrane and analyses of their modes of action.

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06717
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47050:Environmental and natural pharmaceutical resources-related
• Research Institution: The University of Tokyo
• Principal Investigator: Nishimura Shinichi 東京大学, 大学院農学生命科学研究科(農学部), 講師 (30415260)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 生理活性化合物 / 天然物 / 生体膜 / 膜脂質

Outline of Final Research Achievements

Compounds that target the cell membrane with unique modes of action were explored from natural sources. First, 5aTHQs, actinomycete metabolites, were revealed to form aggregates and bind to lipid membranes. Notably, their membrane binding and anti-yeast activities were enhanced when congeners were mixed. This seems to explain why congeners of natural products are produced. Next, amantelide A, a marine cyanobacterial metabolite, was found to bind to lipid membranes containing sterols. Its molecular mechanism for the sterol recognition seems to be novel. Third, amphiol, an antifungal fungal pigment, was discovered. This compound may target fungal cell membrane although a precise analysis remains to be done. In addition to these findings, unique bioactivities of unusual fatty acids were investigated to suggest a highly specific molecular target for these molecules.

Free Research Field

天然物化学

Academic Significance and Societal Importance of the Research Achievements

生体膜を構成する膜脂質はゲノムに直接コードされておらず解析手法に限りがあることから、その機能の理解は遅れています。一方で膜脂質は感染症治療薬の標的であり、新しい膜脂質標的型の化合物が求められています。本研究では膜脂質に作用して抗真菌活性を示す新しい生理活性化合物を取得し、それらのユニークな表現型と作用メカニズムの一端を解明しました。取得した化合物を用いた膜脂質の機能理解と抗真菌剤開発への貢献が期待されます。