A case study of evolutionary variability and determinism among type III polyketide synthases

Abstract

Repeated evolution of the same enzymatic activity represents a powerful model of determinism across diverse lineages, yet its underlying evolutionary trajectories remain poorly understood. Here we identified three 3-oxo-glutaric acid (OGA)-forming type III polyketide synthases (PKSs) from Brassicaceae plants through in vitro enzyme assays. Structure–function analysis combined with comparative genomics indicates a strong correlation between OGA- and triacetic acid lactone (TAL)-forming activities during the evolution of these PKSs. An evolutionary change in a key active-site residue enables a functional switch from TAL-forming activity to OGA-forming activity. Intriguingly, further chalcone synthase activity assays and expanded exploration of PKSs from additional plant lineages suggest that OGA-forming PKSs may have evolved repeatedly from the intrinsic TAL-forming activity of chalcone synthases in a lineage-specific manner. This evolutionary feature may help explain the recurrent emergence of OGA-forming PKSs in vascular plants and provide insight into the trajectories underlying the independent evolution of homologous isoenzymes in plants. This study suggests that 3-oxo-glutaric acid-forming polyketide synthases evolved repeatedly from the intrinsic triacetic acid lactone-forming activity of chalcone synthases through independent, lineage-specific evolutionary events.