Studies on the biosyntheses of fungal dimeric anhydrides

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K05836
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 38040:Bioorganic chemistry-related
• Research Institution: Tohoku University (2021); Hokkaido University (2019-2020)
• Principal Investigator: Ozaki Taro 東北大学, 薬学研究科, 准教授 (40709060)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 生合成

Outline of Final Research Achievements

In this study, the biosynthetic pathway of fungal dimeric anhydrides such as an antifungal agent zopfiellin were analyzed. As reported in previous studies, maleic anhyride monomers are constructed by the action of polyketide synthase, alkylcitrate synthase, alkylcitrate dehydratase. After the biogenesis of monomers, ketosteroid isomerase-like enzymes (KIs) catalyze dimerization, yielding maleic anhydride dimers. KI in each pathway catalyzes dimerization in distinct mode, showing that KIs are key enzymes for structural diversification of fungal maleic anhydrides. Non-heme iron/alpha-ketoglutarate dependent dioxygenases are also involved in the late stage modifications, further diversifying the structure to furnish structures of natural products.

Free Research Field

天然物化学

Academic Significance and Societal Importance of the Research Achievements

本研究課題では、糸状菌が生産する生物活性物質の中でも特にユニークな化学構造を持ち、多くの部分が未解明だった酸無水物多量体の生合成経路を明らかにした点に意義がある。近年、酵素反応や生合成系を利用した物質生産が着目されているが、生合成経路を明らかにし、異種宿主内で生合成経路の再構築にも成功したことから、形質転換体の培養による化合物の持続的な供給が可能になる。また、将来的には経路の改変や再設計などにより、天然物用の構造を持つ新規物質の創製にもつながりうる重要な成果である。