Engineering Starter Units in Aromatic Polyketides

Abstract

The starter unit represents an attractive site in the aromatic polyketide scaffold for introducing alternative chemical functionalities. Most aromatic polyketide synthases (PKSs) are primed by acetate through the decarboxylative condensation of malonyl-ACP. Nonacetate-primed PKSs have been sequenced and characterized. Precursor-directed biosynthesis and heterologous recombination of initiation and elongation modules have led to the engineered biosynthesis of completely new aromatic polyketide scaffolds containing novel starter units, as well as the regioselective modification of known aromatic polyketides.