Investigation of a polyprenyl/dolichyl phosphate mannose synthase involved in bacterial protein mannosylation

Glycosylation is one of the most prevalent post-translational modifications that significantly affects protein structure, localisation and function. Protein mannosylation is particularly crucial for the development of healthy organisms, and it is also involved in the pathogenesis of infectious diseases such as tuberculosis and meningitis. Protein mannosylation is carried out in various organisms by highly specific glycosyltransferases (GTs) that utilise polyprenyl phosphate mannosyl donor substrates, such as undecaprenyl phosphate mannose in prokaryotes and dolichyl phosphate mannose in eukaryotes. This research work concerned the investigation of the function and the structure of polyprenyl/dolichyl phosphate mannose synthase enzymes. These catalyse the conversion of polyprenyl/dolichyl phosphate substrates to the corresponding β-mannosyl phospholipids using GDP-mannose. Currently, there is scarce information about this enzyme class due to challenges associated to protein solubility, stability and limited substrate availability. Insights into the structure and the function of these enzymes would greatly aid the development of glycosyltransferases as both biocatalysts and as novel therapeutics targeting glycosylation ... (continues)