Pentaketide chromone synthase (PCS) from Aloe arborescens is a novel plant-specific type IIIpolyketide synthase (PKS) that produces 5,7-dihydroxy-2-methylchromone from five molecules of malonyl-CoA. On the basis of the crystal structures of wild-type and M207G mutant PCS, the F80A/Y82A/M207Gtriple mutant was constructed and shown to produce an unnatural novel nonaketide naphthopyrone bysequential condensations of nine molecules of malonyl-CoA. This is the first demonstration of the formationof a nonaketide by the structurally simple type III PKS. A homology model predicted that the active-sitecavity volume of the triple mutant is increased to 4 times that of the wild-type PCS.
