POLYKETIDE SYNTHESIS - PROSPECTS FOR HYBRID ANTIBIOTICS

Polyketides fall into two structural classes: aromatic and complex. Th e former are built mainly from acetate units through a reiterative pro cess wherein the beta-carbonyl groups formed after each condensation c ycle are left largely unreduced. Complex polyketides are composed of a cetates, propionates, or butyrates, and the extent of beta-carbonyl re duction varies from one cycle to the next. Two themes for polyketide s ynthases are emerging. Aromatic PKSs are determined by four to six gen es encoding mono- or bifunctional enzymes; one PKS complex is used for all synthesis steps. Complex PKSs are composed of several mulitfuncti onal polypeptides that contain enzymatic domains for the condensation and reduction steps; each domain is used at a unique step in the pathw ays, and the extent of beta-carbonyl processing depends on the functio nal domains operating at that cycle. Mutations rendering certain domai ns nonfunctional have been introduced into genes for complex polyketid es, resulting in the production of novel molecules.