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Publication Abstract from PubMed

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.

Unexpected Activities of CYP152 Peroxygenases towards Non-carboxylic Substrates Reveal Novel Substrate Recognition Mechanism and Catalytic Versatility.,Jiang Y, Gong P, Li Z, Li Z, Li Y, Wang B, Huang H, Peng W, Gao X, Li S Angew Chem Int Ed Engl. 2025 Apr 19:e202506614. doi: 10.1002/anie.202506614. PMID:40252015^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.