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http://dx.doi.org/10.4062/biomolther.2009.17.2.156

Self-Sufficient Catalytic System of Human Cytochrome P450 4A11 and NADPH-P450 Reductase  

Han, Song-Hee (Department of Biological Sciences, Konkuk University)
Eun, Chang-Yong (Department of Biological Sciences, Konkuk University)
Han, Jung-Soo (Department of Biological Sciences, Konkuk University)
Chun, Young-Jin (College of Pharmacy, Chung-Ang University)
Kim, Dong-Hyun (School of Biological Sciences and Technology, Chonnam National University)
Yun, Chul-Ho (School of Biological Sciences and Technology, Chonnam National University)
Kim, Dong-Hak (Department of Biological Sciences, Konkuk University)
Publication Information
Biomolecules & Therapeutics / v.17, no.2, 2009 , pp. 156-161 More about this Journal
Abstract
The human cytochrome P450 4A11 is the major monooxygenase to oxidize the fatty acids and arachidonic acid. The production of 20-hydroxyeicosatetraenoic acid by P450 4A11 has been implicated in the regulation of vascular tone and blood pressure. Oxidation reaction by P450 4A11 requires its reduction partners, NADPH-P450 reductase (NPR). We report the functional expression in Escherichia coli of bicistronic constructs consisting of P450 4A11 encoded by the first cistron and the electron donor protein, NPR by the second. Typical P450 expression levels of wild type and several N-terminal modified mutants was observed in culture media and prepared membrane fractions. The expression of functional NPR in the constructed P450 4A11: NPR bicistronic system was clearly verified by reduction of nitroblue tetrazolium. Membrane preparation containing P450 4A11 and NPR efficiently oxidized lauric acid mainly to $\omega$-hydroxylauric acid. Bicistronic coexpression of P450 4A11 and NPR in E. coli cells can be extended toward identification of novel drug metabolites or therapeutic agents involved in P450 4A11 dependent signal pathways.
Keywords
P450 4A11; Bicistronic expression; Lauric acid; Arachidonic acid;
Citations & Related Records
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Times Cited By Web Of Science : 2  (Related Records In Web of Science)
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