Planta Med 2012; 78 - PH15
DOI: 10.1055/s-0032-1320674

Human metabolites of natural products generated by bacterial CYP102A1 mutants

CH Yun 1, HI Yim 1, BY Park 1, JY Kang 1, SY Kim 1, HY Jo 1, G Cha 1, SH Ryu 1
  • 1School of Biological Sciences and Technology, Chonnam National University, Gwangju 500–757, Republic of Korea

Cytochrome P450 BM3 (CYP102A1) from Bacillus megaterium is a soluble, catalytically self-sufficient monooxygenase which contains a heme monooxygenase domain and a diflavin reductase domain on a single polypeptide chain. In recent studies, several CYP102A1 mutants were found to generate human metabolites by oxidizing various kinds of drugs. CYP102A1 has therefore become the prime candidate monooxygenase for directed evolution and rational design towards biocatalytic applications. In this study, a set of CYP102A1 mutants were found to oxidize several natural products with chemopreventive potential such as stilbenoids (resveratrol, pterostilbene) and flavonoids (naringenin, genistein), to make human metabolites, mainly monohydroxylated metabolites. These results demonstrate that CYP102A1 mutants can be used to produce human metabolites of natural products, which can be used in several industrial fields including drug development. [This research was supported by Bio-industry Technology Development Program (No. 111052–04–1-SB010), Ministry for Food, Agriculture, Forestry and Fisheries, Republic of Korea.].