One-Pot Enzymatic Total Synthesis of Presteffimycinone, an Early Intermediate of the Anthracycline Antibiotic Steffimycin Biosynthesis.

Early acting cyclases play critical roles in programming the polyketide biosynthesis toward certain, distinguished scaffolds. Starting from acetyl-CoA and malonyl-CoA, a one-pot enzymatic total synthesis of an anthracyclinone scaffold, presteffimycinone, was achieved by mixing polyketide synthase (PKS) and early post-PKS enzymes from the biosynthetic pathways of three different types of type II-PKS driven anticancer antibiotics, namely, the mithramycin (aureolic acid-type), gilvocarcin (rearranged angucycline-type), and steffimycin (anthracycline) pathways.