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Generation of the Human Metabolite Piceatannol from the Anti-Cancer Preventive Agent Resveratrol by Bacterial Cytochrome P450 Bm3
( Dong Hyun Kim ) , ( Tae Ho Ahn ) , ( Heung Chae Jung ) , ( Jae Gu Pan ) , ( Chul Ho Yun )
연구논문집 2009권 1-28(28pages)
UCI I410-ECN-0102-2012-510-000860117
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Recently, the wild-type and mutant forms of cytochrome P450 BM3 (CYP102A1) from Bacillus megaterium were found to metabolize various drugs through reactions similar to those catalyzed by human P450 enzymes. Therefore, it was suggested that CYP102A1 can be used to produce large quantities of the metabolites of human P450-catalyzed reactions. trans-Resveratrol, an anti-cancer preventive agent, is oxidized by human P450 1A2 to produce two major metabolites, piceatannol and another hydroxylated product. In this report, we show that the oxidation of trans-resveratrol, a human P450 1A2 substrate, is catalyzed by wild-type and a set of CYP102A1 mutants. One major hydroxylated product, piceatannol, was produced as a result of the hydroxylation reaction. Other hydroxylated products were not produced. Piceatannol formation was confirmed by HPLC and GC-MS by comparing the metabolite to the authentic piceatannol compound. These results demonstrate that CYP102A1 mutants can be used to produce piceatannol, a human metabolite of resveratrol.

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