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

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 C16 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 C22 aromatic octaketides from the C6–C2 phenylacetyl starter, as well as a novel C19 heptaketide benzophenone from the C6–C1 benzoyl starter.