GDPmannuronate

GDP-mannuronate, or GDP-ManA, is the guanosine diphosphate ester of D-mannuronic acid. It is a nucleotide-activated sugar used as an essential precursor in the biosynthesis of alginate, a negatively charged exopolysaccharide produced by certain bacteria.

Biological context and role. GDP-mannuronate is most notably involved in alginate production by mucoid strains of Pseudomonas aeruginosa and by some Azotobacter species. Alginate forms part of the biofilm matrix and contributes to the mucoid phenotype that enhances persistence in hostile environments, including the lungs of people with cystic fibrosis. The monomer units in alginate comprise mannuronate and its C-5 epimer guluronate, and GDP-mannuronate provides the mannuronate units used by the polymerization machinery to build the alginate polymer at the cell surface.

Biosynthesis. In bacteria capable of alginate production, GDP-mannuronate is generated within the alginate biosynthesis pathway from GDP-mannose and then supplied to the membrane-associated polymerase complex that constructs the alginate chain. Enzymes encoded within the alginate gene cluster catalyze the conversion and incorporation of these activated sugars into growing polysaccharide chains, with subsequent epimerization creating blocks of guluronate units.

Importance and research. GDP-mannuronate is central to understanding bacterial biofilms and alginate-related mucoidy, which are linked to chronic infections and antibiotic tolerance. As such, the GDP-mannuronate–alginate pathway is a focus of research aiming to develop anti-biofilm strategies and to engineer alginate production for industrial applications.