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Drug Metabolism and Disposition Fast Forward
First published on July 31, 2008; DOI: 10.1124/dmd.108.021220

0090-9556/08/3611-2166-2170$20.00
DMD 36:2166-2170, 2008

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SHORT COMMUNICATION

Generation of Human Metabolites of 7-Ethoxycoumarin by Bacterial Cytochrome P450 BM3

Dong-Hyun Kim, Keon-Hee Kim, Dae-Hwan Kim, Kwang-Hyeon Liu, Heung-Chae Jung, Jae-Gu Pan, and Chul-Ho Yun

School of Biological Sciences and Technology and Hormone Research Center, Chonnam National University, Gwangju, Republic of Korea (Do.-H.K., K.-H.K., Da.-H.K., C.-H.Y.); Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea (K.-H.L.); and Systems Microbiology Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea (H.-C.J., J.-G.P.)

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.

Address correspondence to: Chul-Ho Yun, School of Biological Sciences and Technology and Hormone Research Center, Chonnam National University, Gwangju 500-757, Republic of Korea. E-mail: chyun{at}jnu.ac.kr




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D.-H. Kim, T. Ahn, H.-C. Jung, J.-G. Pan, and C.-H. Yun
Generation of the Human Metabolite Piceatannol from the Anticancer-Preventive Agent Resveratrol by Bacterial Cytochrome P450 BM3
Drug Metab. Dispos., May 1, 2009; 37(5): 932 - 936.
[Abstract] [Full Text] [PDF]


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