Biochemistry and Chemoinformatics Guided Classification of Hirsutane Sesquiterpenes Isolated from Mushroom

作     者：Liu, Yaping Nishishita, Jumpei Liu, Chengwei Oikawa, Hideaki Minami, Atsushi 

作者机构：Hokkaido Univ Fac Sci Dept Chem Sapporo 0600810 Japan Tokyo Inst Technol Dept Chem Tokyo 1528551 Japan Northeast Forestry Univ Coll Life Sci Key Lab Enzyme & Enzyme Like Mat Engn Heilongjiang Harbin 150040 Peoples R China Inst Sci Tokyo Dept Chem Tokyo 1528551 Japan 

出 版 物：《JACS AU》 (JACS. Au.)

年 卷 期：2025年第5卷第2期

页      面：740-746页

基　　金：Japan Society for the Promotion of Science [JP22H02204, JP23H04533, JP24H01741, JP23K23471, JP19H02891] Japan Society for the Promotion of Science, KAKENHI National Natural Science Foundation of China 

主　　题：basidiomycota fungi hirsutanes heterologousexpression chemoinformatics 

摘      要：Hirsutanes are mushroom-derived sesquiterpenes with a characteristic 5-5-5 tricyclic ring skeleton. To date, more than 70 derivatives have been isolated from nature. In this study, we applied heterologous expression, in vitro enzymatic reactions, and biotransformation to characterize the function of nine enzymes involved in the synthesis of anhydroarthrosporone and six novel hirsutanes. The elucidated biosynthesis involves oxidative modifications of the A-ring followed by structural diversification of the B- and C-rings. Most importantly, biosynthetic pathways provide crucial insights into the classification and organization of isolated hirsutanes. We successfully classified 69 natural hirsutanes into three groups based on their A-ring modification patterns. Our classification covered 92% of the natural hirsutanes. A comprehensive understanding of their biosynthesis will provide opportunities to isolate structurally diverse hirsutanes using genetic engineering techniques.