Accessing Mammalian Drug Metabolites Using PolyCYPs® Enzymes

Presented at: ISSX meeting, Portland 2019

This poster illustrates the application of a new biocatalysis kit, PolyCYPs®, to enable scalable synthesis of CYP-derived metabolites of drugs. The PolyCYPs platform is comprised of a set of recombinant cytochrome P450 enzymes and redox partners cloned from some of the talented actinomycetes in Hypha’s biotransformation panel. Enzymes in the kit catalyze the oxidation of a wide variety of substrate types to generate multiple mammalian and microbial-derived CYP metabolites.

The poster features application of selected PolyCYPs isoforms to produce oxidized human metabolites of drugs. Further, the utility of PolyCYPs enzymes for introducing oxygen into a drug candidate as part of a late-stage functionalization program is illustrated, in which derivatives can be generated in parallel which may possess superior properties such as improved metabolic stability and LLE (lipophilic ligand efficiency), and for exploration of structure-activity relationships.