A flavin-monooxygenase catalyzing oxepinone formation and the complete biosynthesis of vibralactone

doi:10.1038/s41467-023-39108-x

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	A flavin-monooxygenase catalyzing oxepinone formation and the complete biosynthesis of vibralactone
	Feng,Ke-Na; Zhang,Yue; Zhang,Mingfang; Yang,Yan-Long; Liu,Ji-Kai; Pan,Lifeng; Zeng,Ying
	2023
发表期刊	NATURE COMMUNICATIONS
ISSN	2041-1723
卷号	14 期号:1 页码:3436
摘要	Vibralactone is a strong lipase inhibitor and a bicyclic beta-lactone containing an oxepinone ring, whose biosynthetic construction was unknown. Here the authors identify an oxepinone-building flavin monooxygenase VibO that is involved in the biosynthesis of vibralactone, and determine its X-ray crystal structure. 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. Cyclization of 3 forms vibralactone (1) whose beta-lactone-fused bicyclic core originates from 4-hydroxybenzoate, yet it remains elusive how 4-hydroxybenzoate is converted to 3 especially for the oxepinone ring construction in the biosynthesis of 1. In this work, using activity-guided fractionation together with proteomic analyses, we identify an 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 of 3. 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. Computational modeling and solution studies provide insight into the likely VibO active site geometry, and suggest possible involvement of a flavin-C4a-OO(H) intermediate.
关键词	ENZYMATIC TOTAL-SYNTHESIS PHENOL HYDROXYLASE PANCREATIC LIPASE CRYSTAL-STRUCTURE INHIBITOR LACTONE FERMENTATIONS GILVOCARCIN METABOLITES
学科领域	Science & Technology - Other Topics
DOI	10.1038/s41467-023-39108-x
WOS记录号	WOS:001003866300026
引用统计	被引频次：4[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74867
专题	中国科学院昆明植物研究所
推荐引用方式 GB/T 7714	Feng,Ke-Na,Zhang,Yue,Zhang,Mingfang,et al. A flavin-monooxygenase catalyzing oxepinone formation and the complete biosynthesis of vibralactone[J]. NATURE COMMUNICATIONS,2023,14(1):3436.
APA	Feng,Ke-Na.,Zhang,Yue.,Zhang,Mingfang.,Yang,Yan-Long.,Liu,Ji-Kai.,...&Zeng,Ying.(2023).A flavin-monooxygenase catalyzing oxepinone formation and the complete biosynthesis of vibralactone.NATURE COMMUNICATIONS,14(1),3436.
MLA	Feng,Ke-Na,et al."A flavin-monooxygenase catalyzing oxepinone formation and the complete biosynthesis of vibralactone".NATURE COMMUNICATIONS 14.1(2023):3436.

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