Enzyme Evolution in Secondary Metabolism

Abstract

Despite a deep overall understanding of the evolution of enzyme function, very little work has specifically focused on the evolution of enzymes in secondary metabolism. This knowledge gap in such a biotechnologically relevant group of enzymes is in contrast with our understanding of the genetic, chemical, and biophysical mechanisms driving the enzymatic synthesis of secondary metabolites. In recent years, evolutionary thinking has transformed this otherwise mechanistically-dominated field, stimulating progress towards deciphering the evolutionary forces driving the vast chemical diversity synthesized by secondary metabolism. Here, we review emerging concepts that have appeared over the last 10 years concerning the evolution of secondary metabolism, moving beyond early, speculative proposals of the evolutionary relationships of enzymes based largely in circumstantial observations. Although our emphasis is mainly at the enzymatic level, the context in which these unique proteins exert their catalytic activities is provided, as well as applications of evolutionary lessons for synthetic biology.