Broadening glycosylation applications
Glycosylation is the process whereby a sugar molecule is attached to a macromolecule, and is catalysed by specialised enzymes referred to as glycotransferases. These post-translational modifications confer novel structural and functional properties to the modified molecules.Lectins are carbohydrate-binding proteins which recognise specific sugar moieties on macromolecules and mediate biological recognition phenomena. The EU-funded FLYGLYGAN project used certain fungal lectins to unveil the glycosylation pathways in the fruit fly Drosophila melanogaster.Scientists screened various lectins to find that only a couple were toxic when fed to Drosophila. Detailed investigation into the mechanism behind the lack of toxicity suggested that Drosophila could generate and express target glycans for these lectins. Additional mechanisms such as enzymes implicated in glycosphingolipid biosynthesis were found to be responsible for the toxic reaction against the Marasmius oreades agglutinin (MOA) lectin.By focusing on glycans encountered in the neuromuscular junction, a strong association was found between lectins and the glycotransferase enzymes that catalyse the addition of the lectin-target glycan. This was validated through loss-of-function experiments.Collectively the FLYGLYGAN work showed that genetics analysis can link genes encoding glycosyltransferases to the glycans they generate. Also, it was possible to identify novel proteins with candidate glycosyltransferase activity. Given the chemical and medical applicability of bioactive glycans and glycoconjugant biosynthesis, the outcome of the study is expected to significantly expand these biotechnology fields.
Keywords
Glycan, glycotransferase, lectins, Drosophila, biosynthesis, bioactive
