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Int. J. Mol. Sci. 2012, 13(12), 15901-15924; doi:10.3390/ijms131215901
Review

Optimization of the Bacterial Cytochrome P450 BM3 System for the Production of Human Drug Metabolites

 and *
Received: 27 September 2012; in revised form: 1 November 2012 / Accepted: 13 November 2012 / Published: 28 November 2012
(This article belongs to the Special Issue Enzyme Optimization and Immobilization)
Abstract: Drug metabolism in human liver is a process involving many different enzymes. Among them, a number of cytochromes P450 isoforms catalyze the oxidation of most of the drugs commercially available. Each P450 isoform acts on more than one drug, and one drug may be oxidized by more than one enzyme. As a result, multiple products may be obtained from the same drug, and as the metabolites can be biologically active and may cause adverse drug reactions (ADRs), the metabolic profile of a new drug has to be known before this can be commercialized. Therefore, the metabolites of a certain drug must be identified, synthesized and tested for toxicity. Their synthesis must be in sufficient quantities to be used for metabolic tests. This review focuses on the progresses done in the field of the optimization of a bacterial self-sufficient and efficient cytochrome P450, P450 BM3 from Bacillus megaterium, used for the production of metabolites of human enzymes. The progress made in the improvement of its catalytic performance towards drugs, the substitution of the costly NADPH cofactor and its immobilization and scale-up of the process for industrial application are reported.
Keywords: cytochromes P450; drug metabolite; active metabolite; toxicity test; adverse drug reactions cytochromes P450; drug metabolite; active metabolite; toxicity test; adverse drug reactions
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Di Nardo, G.; Gilardi, G. Optimization of the Bacterial Cytochrome P450 BM3 System for the Production of Human Drug Metabolites. Int. J. Mol. Sci. 2012, 13, 15901-15924.

AMA Style

Di Nardo G, Gilardi G. Optimization of the Bacterial Cytochrome P450 BM3 System for the Production of Human Drug Metabolites. International Journal of Molecular Sciences. 2012; 13(12):15901-15924.

Chicago/Turabian Style

Di Nardo, Giovanna; Gilardi, Gianfranco. 2012. "Optimization of the Bacterial Cytochrome P450 BM3 System for the Production of Human Drug Metabolites." Int. J. Mol. Sci. 13, no. 12: 15901-15924.



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