Reports: G4
45864-G4 Chemical Mechanism of a Unique, Cofactor-Independent Decarboxylase
For the last 12 months, this PRF grant has continued to fund our exploration of catalytic promiscuity in sugar kinases. We have also begun to search for additional examples of promiscuity harbored within the genome of the common proteobacterium, Escherichia coli. We have succeeded in identifying several genes whose overexpression confers resistance to bromoacetic acid, a toxic small molecule that provides a useful model for antibiotics and anthropogenic compounds. Our laboratory has demonstrated that a number of putative membrane pumps confer resistance to bromoacetic acid. In addition, we have found that MurA, a key enzyme in the biosynthesis of the the bacterial peptidoglycan layer, is the primary target of bromoacetate. We are in the process of expanding upon these preliminary results by searching for latent antibiotic resistance determinants that may result from catalytic promiscuity. Significantly, this PRF award has provided us with support necessary for the collection of preliminary data that we will use in an upcoming submission to the NIH.
