Drug Metabolite Generation Using a Laboratory Evolved NADPH Independent Cytochrome P450: Application of in vitro and in silico Approaches
Nyaradzo T. L. Chigorimbo-Murefu,
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
Keywords: Biocatalysis, Cytochrome p450, in silico predictions, in vitro drug metabolism, metabolite generation, recombinant
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