platenolide-i and protylonolide

The lactone rings of the polyketides platenolide and tylactone are synthesized by condensation of acetate-, proprionate-, and butyrate-derived precursors. A hybrid tylactone/platenolide synthase was constructed to determine if the choice of substrate is programmed by the polyketide synthase and to ascertain if a substrate different than that normally used in the first step of platenolide synthesis could be incorporated into the final polyketide. In this work, we report the successful incorporation of a propionate in place of the acetate normally used in the first step of platenolide synthesis. This result demonstrates that polyketide synthases choose a particular substrate at defined steps and provides strong evidence that substrate choice is programmed by the acyl transferase domain of a large, multifunctional polyketide synthase.

Topics: Acyl Coenzyme A; Acyltransferases; Anti-Bacterial Agents; Lactones; Macrolides; Malonyl Coenzyme A; Multienzyme Complexes; Open Reading Frames; Recombinant Proteins; Sequence Deletion; Streptomyces; Substrate Specificity; Tylosin