Generation of human metabolites of 7-ethoxycoumarin by bacterial cytochrome P450 BM3

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Title
Generation of human metabolites of 7-ethoxycoumarin by bacterial cytochrome P450 BM3
Author(s)
D H Kim; K H Kim; D H Kim; K H Liu; Heung Chae Jung; Jae Gu Pan; C H Yun
Bibliographic Citation
Drug Metabolism and Disposition, vol. 36, no. 11, pp. 2166-2170
Publication Year
2008
Abstract
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.
ISSN
0090-9556
Publisher
Amer Soc Pharmacology Experimental Therapeutics
DOI
http://dx.doi.org/10.1124/dmd.108.021220
Type
Article
Appears in Collections:
Division of Bio Technology Innovation > SME Support Center > 1. Journal Articles
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