Enrichment of new alkane oxidizing bacterial strains for human drug metabolite production

Human metabolites of active pharmaceutical ingredients (APIs) are of high interest for pharmacokinetic and toxicological studies. Moreover, some API metabolites are also under investigation as possible next generation drugs. However, often highly selective chemical reactions, e.g. stereo- and regioselective hydroxylations are required to enable the production of these compounds and biocatalysis offers the only feasible synthetic approach. Screening microorganisms to discover new catalytic activities is usually a time consuming task and the outcome is unpredictable. Aerobic alkane oxidizing bacteria depend on their ability to hydroxylate hydrocarbons to introduce such non-activated carbon sources to their central metabolic pathways. Hence, we expected that alkane metabolizers generally might also enable hydroxylation of other substrates, e.g. APIs. Based on this working hypothesis a collection of alkane metabolizing strains was established, roughly classified by 16S rDNA sequencing and screened for metabolite production of seven different pharmacological compounds. Several active strains were found, metabolizing dextromethorphan, harmine, phenacetin and tolbutamide. Overall, almost 30% of the new isolated strains showed activity with at least one of the 7 substrates.