Highly Selective Hydroxylation of Benzene to Phenol by Wild-type Cytochrome P450BM3 Assisted by Decoy Molecules

摘要

Phenol is a key intermediate in industry for the synthesis of drugs, dyes, and functional polymers. Because phenol is currently produced by the cumene process, which involves high energy consumption and significant formation of side products such as acetone and methylstyrene, direct hydrox-ylation of benzene has attracted much attention as an alternative method of production. The direct hydroxylation of benzene to phenol using a variety of catalysts, electrochemical oxidation systems, and photochemical systems has thus been extensively investigated. In contrast to many oxidation reactions at high temperature, monooxygenases in nature, such as cytochrome P450, efficiently catalyze the oxidation of inert alkanes and aromatic compounds under mild conditions. Thus, various engineered enzymes have been constructed by site-directed mutagenesis, random mutagenesis, and chemical modification. Biocatalysts for exclusive hydroxylation of the benzene ring using natural enzymes, if they could be developed, would be ideal systems for the production of phenol. Herein we report an efficient and selective hydroxylation of benzene to phenol catalyzed by wild-type cytochrome P450BM3 (P450BM3) with the assistance of decoy molecules.