Yuanyuan Jiang, Piqian Gong, Zijia Li, Zhong Li, Yuxuan Li, Binju Wang, He Huang, Wei Peng, Xiang Gao, Shengying Li
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引用次数: 0
Abstract
Exploring and exploiting the catalytic promiscuity of enzymes is a central topic and captivating challenge in enzymology. CYP152 peroxygenases are attractive biocatalysts for diverse reactions under mild conditions using H2O2 as cofactor. However, their substrate scope is limited by a carboxyl group required for substrate assisted acid-base catalysis, following the well-accepted principle that heme-dependent H2O2-utilizing enzymes employ a carboxyl group within their active sites to facilitate H2O2 activation. Herein, we reveal for the first time that several CYP152 family members can directly degrade various aromatic pollutants without any carboxyl group, exhibiting novel aromatic hydroxylation and dehalogenation activities. Through crystal structure analysis, isotope tracing experiments, and QM/MM calculations, we elucidate that the phenolic hydroxyl group activated by electron-withdrawing substituent(s) functionally replaces the carboxyl group, forming hydrogen bonds with the conserved arginine leading to Compound I formation. The oxygen atom of the newly formed hydroxyl group originates from water, bypassing the conventional oxygen rebound step. These findings provide first insights into the mechanisms of P450 peroxygenases towards non-carboxylic substrates, expanding our knowledge of biological C-H activation and C-halogen bond cleavage beyond canonical P450 reactions. This discovery holds immense potential for harnessing these enzymes in innovative strategies for industrial biocatalysis and environmental remediation.
期刊介绍:
Angewandte Chemie, a journal of the German Chemical Society (GDCh), maintains a leading position among scholarly journals in general chemistry with an impressive Impact Factor of 16.6 (2022 Journal Citation Reports, Clarivate, 2023). Published weekly in a reader-friendly format, it features new articles almost every day. Established in 1887, Angewandte Chemie is a prominent chemistry journal, offering a dynamic blend of Review-type articles, Highlights, Communications, and Research Articles on a weekly basis, making it unique in the field.