Beyond ethylmalonyl-CoA: the functional role of crotonyl-CoA carboxylase/reductase homologs in expanding polyketide diversity

This review covers the emerging biosynthetic role of crotonyl-CoA carboxylase/reductase (CCR) homologs in extending the structural and functional diversity of polyketide natural products. CCRs catalyze the reductive carboxylation of α,β-unsaturated acyl-CoA substrates to produce a variety of substituted malonyl-CoA derivatives employed as polyketide synthase extender units. Here we discuss the history of CCRs in both primary and secondary metabolism, the mechanism by which they function, examples of new polyketide diversity from pathway specific CCRs, and the role of CCRs in facilitating the bioengineering novel polyketides.