Aromatic Polyketides Produced by Bacterial Iterative Type I Polyketide Synthases

Polyketides comprise a large and highly diverse group of natural products produced by polyketide synthases (PKSs), and many of these compounds display remarkable biological activities. Although PKSs share a common mechanism in the assembly of polyketides from short carboxylic acid precursors, different types of PKSs have been classified according to their structures and modes of action. This review discusses a growing group of bacterial PKSs that are structurally type I but act in an iterative manner to produce aromatic polyketides. We summarize the genetic and biochemical features of these enzymes and compare them with other types of PKSs with an emphasis on the evolutionary relationship. We also discuss the different mechanisms for polyketide off-loading and the diverse post-PKS modifications on the resulting aromatic rings. Insights into bacterial iterative type I PKSs for aromatic polyketide, formation and the relevant tailoring enzymes may guide rational bioengineering efforts to produce novel natural products.