title: Drug metabolite generation using a laboratory evolved NADPH independent cytochrome P450: application of in vitro and in silico approaches.
abstract: Twelve disparate drugs were subjected to metabolite generation by a laboratory evolved bacterial cytochrome P450 to investigate feasibility of the bacterial CYP to generate drug metabolites. Seven drugs were metabolised by the bacterial cytochromes to give diverse metabolites, which were compared to human metabolites reported in literature. Several non human metabolites were also generated by the bacterial CYP in addition to the known human metabolites. From docking studies and in silico sites of metabolism results, it was shown that the binding mode of the drug molecule and its distance from the active site in the binding pocket of the CYP was important for metabolism. This contribution reports, for the first time, previously uncharacterised metabolites of this bacterial cytochrome and demonstrates the potential usefulness of human CYP-based prediction software when used in combination with bacterial CYPs for metabolite generation.
authors: Nyaradzo T L
authors: NT
authors: Chigorimbo-Murefu
authors: Mathew
authors: M
authors: Njoroge
authors: Stefan
authors: S
authors: Louw
authors: Grace
authors: G
authors: Mugumbate
authors: Institute of Infectious Diseases and Molecular Medicine University of Cape Town, Rondebosch 7701, South Africa. Kelly.Chibale@uct.ac.za.
authors: Kelly
authors: K
authors: Chibale
mesh_terms: D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003198:Computer Simulation; D004926:Escherichia coli / Q000201:enzymology; D006801:Humans; D013058:Mass Spectrometry; D008958:Models, Molecular; D009154:Mutation; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012984:Software; D015262:Xenobiotics / Q000378:metabolism*
chemical_list: D004364:Pharmaceutical Preparations; D011994:Recombinant Proteins; D015262:Xenobiotics; D009251:NADPH-Ferrihemoprotein Reductase