KDO8phosphate

KDO8phosphate is a phosphorylated derivative of 2-keto-3-deoxy-D-manno-octulosonic acid, commonly known as KDO. KDO is a unique nine-carbon sugar acid found primarily in the lipopolysaccharide (LPS) layer of the outer membrane of Gram-negative bacteria. KDO8phosphate is a crucial intermediate in the biosynthesis of KDO and subsequently, LPS.

The synthesis of KDO8phosphate begins with the condensation of arabinose-5-phosphate and phosphoenolpyruvate. This reaction is catalyzed by the enzyme KDO-8-phosphate synthase (KPS). The product, KDO8phosphate, is then dephosphorylated to form KDO by KDO-8-phosphate phosphatase (KPP). KDO is subsequently activated to CDP-KDO, which is then incorporated into the lipid A precursor during LPS assembly.

The KDO core is essential for the structural integrity and function of the Gram-negative bacterial outer membrane. It plays a role in mediating interactions with the environment, such as with host immune systems, and contributes to the barrier function of the cell envelope. Consequently, the enzymes involved in KDO biosynthesis, including KDO8phosphate synthase, are considered potential targets for the development of novel antibiotics. Inhibiting this pathway could disrupt LPS synthesis, leading to bacterial cell death. Research into these enzymes is ongoing to understand their structure, function, and potential as antimicrobial targets.