Researchers in Canada have found an alternative, cheaper way of making complex carbohydrate structures found in biological systems. 

Creating glycan structures using glycosyltransferase enzymes is a useful way to begin to understand their role in biological systems. However the sugar nucleotide substrates needed for glycosyltransferases are expensive. Stephen Withers and co-workers from the University of British Columbia and the National Research Council of Canada have found that nitrophenyl glycosides can be used as alternative, cheaper substrates for these enzymes, as long as a small catalytic amount of the relevant natural substrate is present. The enzyme works by first catalysing the formation of the natural sugar donor from the artificial substrate. 

Glycans are complex carbohydrate structures found in cells, often linked to proteins. The individual carbohydrate building blocks are linked in a variety of stereochemical orientations, a process catalysed by glycosyltransferases. It is very difficult to access these structures with traditional synthetic chemistry, which could be why the role that glycans play in normal and pathological biology remains poorly understood compared to proteins and DNA. 

David Jakeman, an expert in carbohydrate enzymology from Dalhousie University, Canada, explains that glycosyltransferases are involved in a myriad of important biochemical and cellular functions, and this work provides a new solution for their substrate accessibility. 'It removes the need to access sugar nucleotides, which are often synthetically challenging targets, by forming them in situ from synthetically accessible glycosides,' said Jakeman. 

According to Withers, the next step will be to explore the generality of this approach amongst a range of glycosyltransferases. Protein engineering approaches will also be useful to increase rates of reactions using the alternative substrates. 

Katherine Vickers