Biochemical and structural basis for a flavin-monooxygenase catalyzing oxepinone formation and the complete biosynthesis of vibralactone
Research Square (Research Square)(2022)
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