Anthracycline Biosynthesis: Genes, Enzymes and Mechanisms

Abstract

Anthracyclines are an important family of tetracyclic aromatic polyketides produced via a type II iterative polyketide synthase pathway. The polyaromatic aglycones are modified by a variety of tailoring enzymes, including glycosylation with deoxy- and amino deoxysugars. Several of these compounds are presently in clinical use as anticancer drugs. During the last few years important advances in the molecular genetics, structural biology and enzymology of the biosynthetic pathways of anthracyclines have been made. Insights into the mechanistic features of the enzymes involved are expected to have implications for the production of novel compounds with improved therapeutic profiles by combinatorial biosynthesis.