Plant type III polyketide synthases (PKSs) exhibit unusually broad, promiscuous substrate specificities; the structurally simple homodimeric proteins accept a variety of nonphysiological substrates, including aromatic and aliphatic CoA thioesters, to produce an array of chemically and structurally divergent unnatural polyketides. Here we present most recent examples including enzymatic formation of (i) tricyclic and tetracyclic unnatural novel alkaloidal scaffolds by PKS1 from Huperzia serrata, and (ii) a C_<19> hexzketide stilbene and a C_<21> heptaketide chalcone by octaketide synthase (OKS) from Aloe arborescens. Manipulation of the enzyme reactions by combination of the precursor directed biosynthesis and sructure-guided engineering of the enzyme would thus lead to further production of unnatural novel polyketide and alkaloid scaffolds.
