Cytochrome P450 Catalyzes Benzene Ring Formation in the Biosynthesis of Trialkyl‐Substituted Aromatic Polyketides

作者：Yu Yang, Er Juan Zhao, Wanqing Wei, Zi Fei Xu, Jing Shi, Xuan Wu, Bo Zhang, Yasuhiro Igarashi, Rui Jiao, Yong Liang, Ren Xiang Tan, Hui Ming Ge · 发表于：Angewandte Chemie International Edition · 年份：2022 · DOI：10.1002/anie.202214026 · 被引用次数：17 · 研究领域：Microbial Natural Products and Biosynthesis、Plant biochemistry and biosynthesis、Fungal Biology and Applications

Lorneic acid and related natural products are characterized by a trialkyl-substituted benzene ring. The formation of the aromatic core in the middle of the polyketide chain is unusual. We characterized a cytochrome P450 enzyme that can catalyze the hallmark benzene ring formation from an acyclic polyene substrate through genetic and biochemical analysis. Using this P450 as a beacon for genome mining, we obtained 12 homologous type I polyketide synthase (PKS) gene clusters, among which two gene clusters are activated and able to produce trialkyl-substituted aromatic polyketides. Quantum chemical calculations were performed to elucidate the plausible mechanism for P450-catalyzed benzene ring formation. Our work expands our knowledge of the catalytic diversity of cytochrome P450.