Enzymatic formation of unnatural novel polyketide scaffolds by plant-specific type III polyketide synthase

摘要

The catalytic potential of octaketide synthase (OKS), a plant-specific type III polyketide synthase (PKS) from Aloe arborescens, was investigated by phenylacetyl-CoA and benzoyl-CoA as starter substrates. As a result, a novel C_(16) pentaketide coumarin was produced from phenylacetyl-CoA, whereas benzoyl-CoA was not a good substrate of OKS. Remarkably, a structure-guided OKS N222G mutant dramatically extended the product chain length to yield four novel polyketides including C_(22) aromatic octaketides from the C6-C2 phenylacetyl starter, as well as a novel C_(19) heptaketide benzophenone from the C6-C1 benzoyl starter.