RT Journal Article SR Electronic T1 Generation of Human Metabolites of 7-Ethoxycoumarin by Bacterial Cytochrome P450 BM3 JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 2166 OP 2170 DO 10.1124/dmd.108.021220 VO 36 IS 11 A1 Dong-Hyun Kim A1 Keon-Hee Kim A1 Dae-Hwan Kim A1 Kwang-Hyeon Liu A1 Heung-Chae Jung A1 Jae-Gu Pan A1 Chul-Ho Yun YR 2008 UL http://dmd.aspetjournals.org/content/36/11/2166.abstract AB Recently, wild-type and mutant forms of bacterial cytochrome P450 BM3 (CYP102A1) have been found to metabolize various drugs through reactions similar to those catalyzed by human cytochromes P450 (P450s). Therefore, it has been suggested that CYP102A1 may be used to produce large quantities of the metabolites of human P450-catalyzed reactions. In this report, we show that the oxidation of 7-ethoxycoumarin, a typical human P450 substrate, is catalyzed by both wild-type and mutant forms of CYP102A1. Two major products were produced as a result of O-deethylation and 3-hydroxylation reactions. These results demonstrate that CYP102A1 mutants catalyze the same reactions as human P450s. High noncompetitive intermolecular kinetic deuterium isotope effects were observed for 7-ethoxycoumarin O-deethylation in the CYP102A1 system. These results suggest that there is a common mechanism for the oxidation reactions catalyzed by both the bacterial CYP102A1 and human P450 enzymes. The American Society for Pharmacology and Experimental Therapeutics