Glycobiology is dogged by the relative scarcity of synthetic, defined oligosaccharides. Enzyme-catalysed glycosylation using glycoside hydrolases is feasible, but is hampered by the innate hydrolytic activity of these enzymes. Protein engineering methods are applicable, though usually require prior structural knowledge of the target enzyme and the use of powerful computing methods, and/or relies on extensive screening methodologies. Here we describe a straightforward strategy that involves rapid in silico analysis of protein sequences. The method pinpoints a small number (<10) of mutant candidates aimed at diminishing hydrolysis and thus tipping the reaction balance toward transglycosylation. Requiring no other significant prior knowledge of the target enzyme than its sequence, the results reveal that the method is quite generic, allowing the improvement of glycoside hydrolases that act on different α-/β-pyranosides or furanosides. Moreover, the presented data support that mutational hotspots that are validated in one enzyme can be transposed to other related enzymes.