Mutating enzymes from GH families 2, 10, 20, 29, and 51, which represent different clans (A, K and R), led to the successful enhancement of transglycosylation yields (2-to 9-fold compared to WT enzymes) in more than 50% of selected candidates. This powerful demonstration validates our conserved-residue approach and illustrates its applicability to retaining GHs irrespective of the structural fold and the specific mechanism. Moreover, a variety of sugars, D/L-configurations, pyranose/furanose forms and α/β-stereochemistry are tolerated, thus new access to hitherto refractory syntheses is provided. In a rather fast and direct manner, the strategy procured the means to reach transglycosylation yields in the range 50-80%, and thus allowed the high yield synthesis of oligosaccharides such as α-L-Fucp-(1→3)-D-GlcNAc, α-L-Fucp-(1→6)-D-GlcNAc, lacto-N-triose II (LNT2), oligomannosides, oligoxylosides and arabinoxylo-oligosaccharides. Remarkably, in each of the five GHs families targeted, while using reasonable enzyme loadings, it proved possible to obtain at least one mutant displaying enhanced transglycosylation yield.