From O to N: engineering the gap

"Metabolites of drugs often need to be investigated and tested as part of regulated safety assessments during drug development. _N_-glucuronides are a class of metabolites increasingly observed as a significant route of drug elimination and are most likely to exhibit transporter-mediated pharmacologic activity and drug-drug-interactions. However, _N_-glucuronides are often difficult to produce in scalable amounts needed for evaluation during these trials, thereby creating a healthcare need for accessing these metabolites.

Glucuronides are produced by uridine 5'-diphospho-glucuronosyltransferases (UGTs), enzymes expressed by many organisms from microbes to humans to facilitate elimination of xenobiotics. There are many subtypes which catalyse the glucuronidation of different compound types, including UGTs which specifically _N_-glucuronidate drugs.

The project, in collaboration with University College London, addresses this clinical need through provision of engineered UGT-based biocatalytic solutions to provide a mechanism for obtaining scalable quantities of _N_-glucuronide metabolites for characterisation, which will enhance the development and application of new medicines by providing a more comprehensive understanding of a drug's pharmacology, disposition, drug interaction risk and toxicity."