Direct Hydroxylation of Benzene to Phenol by Cytochrome P450BM3 Triggered by Amino Acid Derivatives

• Published in: Angewandte Chemie International Edition 2017-08, Vol.56 (35), p.10324-10329
• Main Authors: Shoji, Osami, Yanagisawa, Sota, Stanfield, Joshua Kyle, Suzuki, Kazuto, Cong, Zhiqi, Sugimoto, Hiroshi, Shiro, Yoshitsugu, Watanabe, Yoshihito
• Format: Article
• Language: English
• Subjects: Amino acids; Amino Acids - chemistry; Amino Acids - metabolism; Benzene; Benzene - chemistry; Benzene - metabolism; Catalysis; Cytochrome; Cytochrome P-450 Enzyme System - metabolism; cytochrome P450; Derivatives; Fatty acids; Hydrocarbons; Hydroxylation; L-Proline; Molecular Structure; phenol; Phenols; Phenols - chemistry; Phenols - metabolism; Phenylalanine; Proline; Turnover rate
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201703461

The selective hydroxylation of benzene to phenol, without the formation of side products resulting from overoxidation, is catalyzed by cytochrome P450BM3 with the assistance of amino acid derivatives as decoy molecules. The catalytic turnover rate and the total turnover number reached 259 min−1 P450BM3−1 and 40 200 P450BM3−1 when N‐heptyl‐l‐proline modified with l‐phenylalanine (C7‐l‐Pro‐l‐Phe) was used as the decoy molecule. This work shows that amino acid derivatives with a totally different structure from fatty acids can be used as decoy molecules for aromatic hydroxylation by wild‐type P450BM3. This method for non‐native substrate hydroxylation by wild‐type P450BM3 has the potential to expand the utility of P450BM3 for biotransformations. Amino acid derivatives, with structures that are totally different from those of fatty acids, efficiently activate cytochrome P450BM3 for the direct hydroxylation of benzene to phenol. The catalytic turnover rate and total turnover number reached 259 min−1 P450BM3−1 and 40 200 P450BM3−1, respectively.