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| Main Authors: | , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Angewandte Chemie (International ed. in English)
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/40252015/ |
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| _version_ | 1868266214127566849 |
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| author | Jiang, Yuanyuan Gong, Piqian Li, Zijia Li, Zhong Li, Yuxuan Wang, Binju Huang, He Peng, Wei Gao, Xiang Li, Shengying |
| author_facet | Jiang, Yuanyuan Gong, Piqian Li, Zijia Li, Zhong Li, Yuxuan Wang, Binju Huang, He Peng, Wei Gao, Xiang Li, Shengying Jiang, Yuanyuan Gong, Piqian Li, Zijia Li, Zhong Li, Yuxuan Wang, Binju Huang, He Peng, Wei Gao, Xiang Li, Shengying |
| collection | PubMed - marine biology |
| contents | Unexpected Activities of CYP152 Peroxygenases Toward Non-carboxylic Substrates Reveal Novel Substrate Recognition Mechanism and Catalytic Versatility. Jiang, Yuanyuan Gong, Piqian Li, Zijia Li, Zhong Li, Yuxuan Wang, Binju Huang, He Peng, Wei Gao, Xiang Li, Shengying Cytochrome P-450 Enzyme System Substrate Specificity Biocatalysis Mixed Function Oxygenases Hydroxylation Molecular Structure Catalytic Domain Crystallography, X-Ray 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 HO 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 HO-utilizing enzymes employ a carboxyl group within their active sites to facilitate HO 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 toward 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. |
| format | Artículo científico |
| id | pubmed_40252015 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Angewandte Chemie (International ed. in English) |
| record_format | pubmed |
| spellingShingle | Unexpected Activities of CYP152 Peroxygenases Toward Non-carboxylic Substrates Reveal Novel Substrate Recognition Mechanism and Catalytic Versatility. Jiang, Yuanyuan Gong, Piqian Li, Zijia Li, Zhong Li, Yuxuan Wang, Binju Huang, He Peng, Wei Gao, Xiang Li, Shengying Cytochrome P-450 Enzyme System Substrate Specificity Biocatalysis Mixed Function Oxygenases Hydroxylation Molecular Structure Catalytic Domain Crystallography, X-Ray Unexpected Activities of CYP152 Peroxygenases Toward Non-carboxylic Substrates Reveal Novel Substrate Recognition Mechanism and Catalytic Versatility. Jiang, Yuanyuan Gong, Piqian Li, Zijia Li, Zhong Li, Yuxuan Wang, Binju Huang, He Peng, Wei Gao, Xiang Li, Shengying Cytochrome P-450 Enzyme System Substrate Specificity Biocatalysis Mixed Function Oxygenases Hydroxylation Molecular Structure Catalytic Domain Crystallography, X-Ray 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 HO 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 HO-utilizing enzymes employ a carboxyl group within their active sites to facilitate HO 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 toward 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. |
| title | Unexpected Activities of CYP152 Peroxygenases Toward Non-carboxylic Substrates Reveal Novel Substrate Recognition Mechanism and Catalytic Versatility. |
| topic | Cytochrome P-450 Enzyme System Substrate Specificity Biocatalysis Mixed Function Oxygenases Hydroxylation Molecular Structure Catalytic Domain Crystallography, X-Ray |
| url | https://pubmed.ncbi.nlm.nih.gov/40252015/ |