Electrocatalytically driven omega-hydroxylation of fatty acids using cytochrome P450 4A1
The cyclic enzymatic function of a cytochrome P450, as it catalyzes the oxygen-dependent metabolism of many organic chemicals, requires the delivery of two electrons to the hemeprotein. In general these electrons are transferred from NADPH to the P450 via an FMN- and FAD-containing flavoprotein (NAD...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1995-08, Vol.92 (17), p.7705-7709 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Faulkner, K M Shet, M S Fisher, C W Estabrook, R W |
| description | The cyclic enzymatic function of a cytochrome P450, as it catalyzes the oxygen-dependent metabolism of many organic chemicals, requires the delivery of two electrons to the hemeprotein. In general these electrons are transferred from NADPH to the P450 via an FMN- and FAD-containing flavoprotein (NADPH-P450 reductase). The present paper shows that NADPH can be replaced by an electrochemically generated reductant [cobalt(II) sepulchrate trichloride] for the electrocatalytically driven omega-hydroxylation of lauric acid. Results are presented illustrating the use of purified recombinant proteins containing P450 4A1, such as the fusion protein (rFP450 [mRat4A1/mRatOR]L1) or a system reconstituted with purified P450 4A1 plus purified NADPH-P450 reductase. Rates of formation of 12-hydroxydodecanoic acid by the electrochemical method are comparable to those obtained using NADPH as electron donor. These results suggest the practicality of developing electrocatalytically dependent bioreactors containing different P450s as catalysts for the large-scale synthesis of stereo- and regio-selective hydroxylation products of many chemicals. |
| doi_str_mv | 10.1073/pnas.92.17.7705 |
| format | Article |
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In general these electrons are transferred from NADPH to the P450 via an FMN- and FAD-containing flavoprotein (NADPH-P450 reductase). The present paper shows that NADPH can be replaced by an electrochemically generated reductant [cobalt(II) sepulchrate trichloride] for the electrocatalytically driven omega-hydroxylation of lauric acid. Results are presented illustrating the use of purified recombinant proteins containing P450 4A1, such as the fusion protein (rFP450 [mRat4A1/mRatOR]L1) or a system reconstituted with purified P450 4A1 plus purified NADPH-P450 reductase. Rates of formation of 12-hydroxydodecanoic acid by the electrochemical method are comparable to those obtained using NADPH as electron donor. 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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1995-08, Vol.92 (17), p.7705-7709 |
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| language | eng |
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| source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Acids Animals Biochemistry Catalysis Cobalt - metabolism Cytochrome P-450 CYP4A Cytochrome P-450 Enzyme System - metabolism Electrochemistry Flavin-Adenine Dinucleotide - metabolism Hydroxylation Kinetics Lauric Acids - metabolism Mixed Function Oxygenases - metabolism NADP - metabolism NADPH-Ferrihemoprotein Reductase - metabolism Organic chemistry Proteins Rats Recombinant Fusion Proteins - metabolism |
| title | Electrocatalytically driven omega-hydroxylation of fatty acids using cytochrome P450 4A1 |
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