Production of diclofenac metabolites by applying cytochrome P450 technology

Cytochrome P450 monooxygenases can catalyze highly regio- and stereo-selective oxidations of many organic compounds. Nevertheless, the scale-up of such biooxidations remains challenging due to the often-low activity, level of expression and stability of P450 biocatalysts. Despite these challenges the demand for these recombinant biocatalysts is increasing, particularly for the production of drug metabolites. Diclofenac is a widely used anti-inflammatory drug that is persistent in the environment along with the 4'-and 5-hydroxy metabolites. Here we report selective hydroxylation of diclofenac to 4'-hydroxy-and 5-hydroxy-diclofenac on multi hundred-gram scale.