NMR metabolic profiling of Aspergillus nidulans to monitor drug and protein activity.

We describe a general protocol for using comparative NMR metabolomics data to infer in vivo efficacy, specificity and toxicity of chemical leads within a drug discovery program. The methodology is demonstrated using Aspergillus nidulans to monitor the activity of urate oxidase and orotidine-5'-phosphate decarboxylase and the impact of 8-azaxanthine, an inhibitor of urate oxidase. 8-azaxanthine is shown to inhibit A. nidulans hyphal growth by in vivo inactivation of urate oxidase.