Research in the Copley lab centers on the molecular evolution of catalysts and metabolic pathways. Enzymes in metabolic pathways are superb catalysts, accelerating chemical reactions by up to 16 orders of magnitude. Many enzymes also catalyze adventitious secondary reactions, simply because active sites are loaded with highly reactive acids, bases, nucleophiles, metal ions, and cofactors. Although these “promiscuous” activities are inefficient, they provide a repertoire of activities that can be drawn upon if conditions change and catalysis of a secondary reaction becomes important for fitness. Projects in the lab seek to identify biochemical and physiological factors that influence the potential for evolution of novel activities from promiscuous enzymes. Other projects focus on the assembly of promiscuous activities into novel combinations that allow microbes to degrade a novel carbon source or bypass a metabolic block caused by a genetic lesion.
molecular evolution of enzymes and metabolic pathways, the evolutionary potential of promiscuous enzymes in the context of complex metabolic and regulatory networks, mechanistic enzymology