2beta-Deoxy-Kdo Is an Inhibitor of the Arabidopsis thaliana CMP-2-Keto-3-Deoxymanno-Octulosonic Acid Synthetase, the Enzyme Required for Activation of Kdo Prior to Incorporation into Rhamnoaalacturonan II

摘要

Gram-negative bacteria utilize the acid sugar 2-keto-3-de-oxymanno-octulosonic acid (Kdo) as an essential component of the lipopolysaccharide (LPS). The enzyme CMP-Kdo synthetase (KdsB) is required to activate Kdo prior to incorporation into the LPS,utilizing Kdo and CTP to form CMP-Kdo and pyrophosphate. The potential of KdsB as a target for antibacterial agents has long been recognized and a number of inhibitors have been developed (Hammond et al., 1987). In eukaryotes, Kdo has been found in the embryophyte cell wall as a component of the pectic polysaccharide rhamnoga-lacturonan II (RG-II) and interestingly as a major component of the cell walls of thecae and scales of prasinophyte algae (Becker et al., 1995). RG-II is a complex, structurally conserved polysaccharide with a critical but as-yet only partially characterized function (O'Neill et al., 2004; Bar-Peled et al., 2012). RG-II has four side chains (A-D) and Kdo occurs only in side chain C, which consists of the disaccharide u-L-Rhap-(1—>5)-a-D-Kdo-(2—>3). The Kdo biosynthesis pathway is conserved in plants but traditional gene knockout approaches to study the effect of disrupting Kdo biosynthesis have been limited by the lethality of these mutants (Delmas et al., 2008).