The Streptomyces peucetius dpsC gene determines the choice of starter unitin biosynthesis of the daunorubicin polyketide

The starter unit used in the biosynthesis of daunorubicin is propionyl coen zyme A (CoA) rather than acetyl-CoA, which is used in the production of mos t of the bacterial aromatic polyketides studied to date. In the daunorubici n biosynthesis gene cluster of Streptomyces peucetius, directly downstream of the genes encoding the beta-ketoacyl:acyl carrier protein synthase subun its, are two genes, dpsC and dpsD, encoding proteins that are believed to f unction as the starter unit-specifying enzymes. Recombinant strains contain ing plasmids carrying dgsC and dpsD, in addition to other daunorubicin poly ketide synthase (PKS) genes, incorporate the correct starter unit into poly ketides made by these genes, suggesting that, contrary to earlier reports, the enzymes encoded by dpsC and dpsD play a crucial role in starter unit sp ecification. Additionally, the results of a cell-free synthesis of 21-carbo n polyketides from propionyl-Coa and malonyl-CoA that used the protein extr acts of recombinant strains carrying other daunorubicin PKS genes to which purified DpsC was added suggest that this enzyme has the primary role in st arter unit discrimination for daunorubicin biosynthesis.