Wei Hui-Ling, Chen Xiao-Ling, Dai Yu, Yang Li, Li Shu-Ming
Philipps-Universität Marburg, Fachbereich Pharmazie, Institut für Pharmazeutische Biologie und Biotechnologie Robert-Koch-Straße 4 35037 Marburg Germany
Haikou Key Laboratory for Research and Utilization of Tropical Natural Products, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences 571101 Haikou P. R. China.
Chem Sci. 2025 Jul 21. doi: 10.1039/d5sc03423j.
The fungal octaketide deoxyverrucosidin shares the same α-pyrone core with several nonaketides, including aurovertins, citreoviridin, and asteltoxin. Deoxyverrucosidin features a unique epoxytetrahydrofuran ring. In this study, we demonstrate that this ring system is formed a flavin-containing monooxygenase-mediated epoxidation on the polyene chain, followed by rearrangement with an epoxide expandase and a second epoxidation on the resulting 2,5-dihydrofuran ring with a cytochrome P450 enzyme. This catalytic cascade differs clearly from the formation of dioxybicyclooctane or tetrahydrofuran motifs in other α-pyrone-containing metabolites, involving one flavin-containing monooxygenase and one hydrolase for up to two rounds of epoxide ring formation and expansion.
真菌八酮脱氧疣孢菌素与几种九酮化合物具有相同的α-吡喃酮核心结构，这些九酮化合物包括黄绿青霉素、桔霉素和黄绿青霉素。脱氧疣孢菌素具有独特的环氧四氢呋喃环。在本研究中，我们证明该环系是由含黄素单加氧酶介导的多烯链环氧化反应形成的，随后通过环氧扩张酶进行重排，并由细胞色素P450酶对生成的2,5-二氢呋喃环进行第二次环氧化反应。这种催化级联反应与其他含α-吡喃酮代谢产物中二氧双环辛烷或四氢呋喃基序的形成明显不同，后者涉及一种含黄素单加氧酶和一种水解酶，进行多达两轮的环氧环形成和扩张。
