A Mushroom P450-Monooxygenase Enables Regioand Stereoselective Biocatalytic Synthesis of Epoxycyclohexenones

doi:10.1002/anie.202313817

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	A Mushroom P450-Monooxygenase Enables Regioand Stereoselective Biocatalytic Synthesis of Epoxycyclohexenones
	Yang,Yan-Long; Zhou,Man; Yang,Lin; Gressler,Markus; Rassbach,Johannes; Wurlitzer,Jacob M.; Zeng,Ying; Gao,Kun; Hoffmeister,Dirk
	2023
发表期刊	ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
ISSN	1521-3773
卷号	62 期号:49
摘要	An epoxycyclohexenone (ECH) moiety occurs in natural products of both bacteria and ascomycete and basidiomycete fungi. While the enzymes for ECH formation in bacteria and ascomycetes have been identified and characterized, it remained obscure how this structure is biosynthesized in basidiomycetes. In this study, we i) identified a genetic locus responsible for panepoxydone biosynthesis in the basidiomycete mushroom Panus rudis and ii) biochemically characterized PanH, the cytochrome P450 enzyme catalyzing epoxide formation in this pathway. Using a PanH-producing yeast as a biocatalyst, we synthesized a small library of bioactive ECH compounds as a proof of concept. Furthermore, homology modeling, molecular dynamics simulation, and site directed mutation revealed the substrate specificity of PanH. Remarkably, PanH is unrelated to ECH-forming enzymes in bacteria and ascomycetes, suggesting that mushrooms evolved this biosynthetic capacity convergently and independently of other organisms. PanH, a cytochrome P450 monooxygenase, was identified and verified as the enzyme responsible for epoxycyclohexenone formation in panepoxydone biosynthesis in the basidiomycete mushroom Panus rudis. A PanH-producing yeast as a biocatalyst enabled an enzymatic approach to synthesize a library of bioactive epoxycyclohexenone compounds.+image
关键词	Biocatalysis Biosynthesis Cytochrome P450 Epoxycyclohexenone Natural Products OPPOSITE FACIAL SPECIFICITY NATURAL-PRODUCTS STREPTOMYCES LL-C10037 BIOSYNTHESIS EPOXYQUINONE CYTOCHROME-P450 FERMENTATION PANEPOXYDONE EPOXIDATION INHIBITION
DOI	10.1002/anie.202313817
收录类别	SCI
WOS记录号	WOS:001095653800001
引用统计	被引频次：8[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/151853/75332
专题	中国科学院昆明植物研究所
推荐引用方式 GB/T 7714	Yang,Yan-Long,Zhou,Man,Yang,Lin,et al. A Mushroom P450-Monooxygenase Enables Regioand Stereoselective Biocatalytic Synthesis of Epoxycyclohexenones[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,2023,62(49).
APA	Yang,Yan-Long.,Zhou,Man.,Yang,Lin.,Gressler,Markus.,Rassbach,Johannes.,...&Hoffmeister,Dirk.(2023).A Mushroom P450-Monooxygenase Enables Regioand Stereoselective Biocatalytic Synthesis of Epoxycyclohexenones.ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,62(49).
MLA	Yang,Yan-Long,et al."A Mushroom P450-Monooxygenase Enables Regioand Stereoselective Biocatalytic Synthesis of Epoxycyclohexenones".ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 62.49(2023).

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