dTDPglucose

dTDP-glucose, short for thymidine diphosphate glucose, is a nucleotide sugar that serves as an activated donor of glucose in various bacterial biosynthetic pathways. It consists of a thymidine diphosphate moiety linked to a glucose residue, typically in the β-anomer form, making it a high-energy sugar donor used by glycosyltransferases.

Biosynthesis and metabolism: dTDP-glucose is formed from glucose-1-phosphate and dTTP by the enzyme thymidylyltransferase (often encoded by the rmlA gene in bacteria). The reaction yields dTDP-glucose and pyrophosphate. This activated sugar is an intermediate in the dTDP-L-rhamnose biosynthetic pathway, where a sequence of enzymes (commonly rmlB, rmlC, and rmlD) converts dTDP-glucose into dTDP-L-rhamnose, a component of many bacterial cell wall polysaccharides and surface structures. Beyond rhamnose production, dTDP-glucose serves as a precursor for other deoxysugars in various organisms, contributing to diverse glycoconjugates.

Occurrence and significance: dTDP-glucose is widespread in bacteria and is central to the assembly of cell wall and capsule polysaccharides, particularly in pathways that generate deoxysugars such as rhamnose. This metabolite is absent from humans, making the dTDP-glucose–dependent pathways attractive targets for antimicrobial drug development. In research, these pathways are studied to understand bacterial virulence, cell wall biosynthesis, and the engineering of microbial glycoconjugates.

regulation and variation: while the core steps are conserved in many bacteria, the exact set of enzymes and regulatory controls can vary among species, reflecting differences in sugar composition and cell surface structures.