Enzyme Promiscuity: Engine of Evolutionary Innovation [Enzymology]

September 10th, 2014 by Pandya, C., Farelli, J. D., Dunaway-Mariano, D., Allen, K. N.

Catalytic promiscuity and substrate ambiguity are keys to evolvability, which in turn is pivotal to the successful acquisition of novel biological functions. Action on multiple substrates (substrate ambiguity) can be harnessed for performance of functions in the cell that supersede catalysis of a single metabolite. These functions include proofreading, scavenging of nutrients, removal of anti-metabolites, balancing of metabolite pools, and establishing system redundancy. In this review we present examples of enzymes that perform these cellular roles by leveraging substrate ambiguity and then present the structural features that support both specificity and ambiguity. We focus on the phosphatases of the haloalkanoate dehalogenase superfamily and the thioesterases of the hotdog-fold superfamily.