Structure-function analysis of biosynthetic enzymes in the biosynthesis of fungal meroterpenoids

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K15703
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 37020:Chemistry and chemical methodology of biomolecules-related
• Research Institution: The University of Tokyo
• Principal Investigator: Mori Takahiro 東京大学, 大学院薬学系研究科(薬学部), 助教 (60734564)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 生合成 / 結晶構造解析 / 酵素

Outline of Final Research Achievements

In this study, we performed biochemical and structural studies of an unique meroterpenoid dioxygenase NvfE, which catalyzes isomerization reaction without utilizing α-KG as a co-factor. Based on these results, we proposed the detailed mechanism of NvfE-catalyzed orthoester formation reaction. In addition, structure and functional analysis of homologue enzyme NvfI, which catalyzes endoperoxide formation reaction, was also succeeded. The detailed mechanistic analysis of the enzyme by using isotope-labeled oxygen and water, and the X-ray crystal structure analysis revealed the structural basis for the endoperoxide formation reaction.

Free Research Field

天然物化学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、これまで非常に困難とされてきた、合理的な酵素機能の改変に成功したものであり、超天然型化合物の酵素合成への利用へとつながることが期待される。特に、エンドペルオキシドを含有する化合物には抗マラリア薬アルテミシニンなど、高い生物活性を示すものが多い。本研究の知見を利用することで、他のエンドペルオキシド含有化合物の生合成の解明につながることも期待される。