Control of stereoselectivity of benzylic hydroxylation catalysed by wild-type cytochrome P450BM3 using decoy molecules

作者：Suzuki Kazuto; Stanfield Joshua Kyle; Shoji Osami^*; Yanagisawa Sota; Sugimoto Hiroshi; Shiro Yoshitsugu; Watanabe Yoshihito^*

来源：Catalysis Science & Technology, 2017, 7(15): 3332-3338.

DOI：10.1039/c7cy01130j

The hydroxylation of non-native substrates catalysed by wild-type P450BM3 is reported, wherein "decoy molecules", i.e., native substrate mimics, controlled the stereoselectivity of hydroxylation reactions. We employed decoy molecules with diverse structures, resulting in either a significant improvement in enantio-selectivity or clear inversion of stereoselectivity in the benzylic hydroxylation of alkylbenzenes and cyclo-alkylbenzenes. For example, supplementation of wild-type P450BM3 with 5-cyclohexylvaleric acid-L-phenylalanine (5CHVA-Phe) and Z-proline-L-phenylalanine yielded 53% (R) ee and 56% (S) ee for indane hydroxylation, respectively, although 16% (S) ee was still observed in the absence of any additives. Moreover, we performed a successful crystal structure analysis of 5CHVA-L-tryptophan-bound P450BM3 at 2.00 angstrom, which suggests that the changes in selectivity observed were caused by conformational changes in the enzyme induced by binding of the decoy molecules.

• 出版日期2017-8-7
• 单位RIKEN