Biochemical and structural basis for a flavin-monooxygenase catalyzing oxepinone formation and the complete biosynthesis of vibralactone

Research Square (Research Square)(2022)

引用 0|浏览0
暂无评分
摘要
Abstract Oxepinone rings represent one of structurally unusual motifs of natural products and the biosynthesis of oxepinones is not fully understood. 1,5-seco-vibralactone (3) features an oxepinone motif and is a stable metabolite isolated from mycelial cultures of the mushroom Boreostereum vibrans. Prior studies confirmed the cyclization of 3 to form vibralactone (1) whose β-lactone-fused bicyclic core originates from 4-hydroxybenzoate (2), yet it is still unknown how 4-hydroxybenzoate is converted to 3 especially for the oxepinone ring construction in the biosynthesis of 1. In this study, using activity-guided fractionation together with proteomic analyses, we identify a NADPH/FAD-dependent monooxygenase VibO as the key enzyme performing a crucial ring-expansive oxygenation on the phenol ring to generate the oxepin-2-one structure. The crystal structure of VibO reveals that it forms a dimeric phenol hydroxylase-like architecture featured with a unique substrate-binding pocket adjacent to the bound FAD. Importantly, relevant biochemical and structural analyses support a Baeyer-Villiger oxidation mechanism adopted by VibO for catalyzing the oxepinone formation. Finally, the complete five-enzyme vibralactone pathway has been functionally reconstructed both in vitro and in Escherichia coli.
更多
查看译文
关键词
oxepinone formation,complete biosynthesis,flavin-monooxygenase
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要