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

摘要

Early acting cyclases play critical roles in programming the polyketide biosynthesis towards 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.