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Evolution of New Enzymes and Metabolic Pathways

Extant enzymes are prodigious catalysts, accelerating chemical reactions by as much as 25 orders of magnitude. However, it is safe to say that no enzyme is perfect in the sense of catalyzing only a single reaction with a single substrate. For enzymes such as P450s and glutathione S-transferases that are involved in detoxification, the ability to catalyze multiple reactions is important for fitness. In other cases, secondary reactions are physiologically irrelevant, either because they are too inefficient to affect fitness or because the enzyme never encounters the substrate. Physiologically irrelevant secondary activities are termed “promiscuous” activities. Promiscuous activities are important because they provide opportunities for evolution of new enzymes and new metabolic pathways, both in nature and in the laboratory. The Copley lab is engaged in several projects that explore the evolutionary potential of promiscuous enzyme activities.