In vitro reconstitution of two essential steps in wall teichoic acid biosynthesis

Abstract

Wall teichoic acids (WTAs) are anionic polymers that decorate the cell walls of many gram-positive bacteria. These structures are essential for survival or virulence in many organisms, which makes the enzymes involved in their biosynthesis attractive targets for the development of new antibacterial agents. We present a strategy to obtain WTA biosynthetic intermediates that involves a combination of chemical and enzymatic transformations. Using these intermediates, we have reconstituted the first two committed steps in the biosynthetic pathway. This work enables the exploration of WTA-synthesizing enzymes as antibiotic targets.