9IY1

P450 BS beta mutant F46A

9IY1 の概要

• エントリーDOI: 10.2210/pdb9iy1/pdb
• 分子名称: Fatty-acid peroxygenase, PROTOPORPHYRIN IX CONTAINING FE, PALMITIC ACID, ... (7 entities in total)
• 機能のキーワード: peroxygenases, oxidoreductase
• 由来する生物種: Bacillus subtilis (strain 168)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 297957.18

構造登録者

Gong, P.Q.,Gao, X. (登録日: 2024-07-29, 公開日: 2025-04-30, 最終更新日: 2025-09-10)

主引用文献

Jiang, Y.,Gong, P.,Li, Z.,Li, Z.,Li, Y.,Wang, B.,Huang, H.,Peng, W.,Gao, X.,Li, S.
Unexpected Activities of CYP152 Peroxygenases Toward Non-carboxylic Substrates Reveal Novel Substrate Recognition Mechanism and Catalytic Versatility.
Angew.Chem.Int.Ed.Engl., 64:e202506614-e202506614, 2025

PubMed 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 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.

PubMed: 40252015
DOI: 10.1002/anie.202506614

実験手法

X-RAY DIFFRACTION (2.29 Å)