Glycosyltransferases as versatile tools to study the biology of glycans.

This article focuses on the use of glycosyltransferases (GTs) as versatile biochemical tools to advance the chemoenzymatic synthesis and glyco-engineering of complex glycans, glycoproteins, and cell surfaces. It details how GTs enable site-, branch-, and glycan subclass-specific installation of defined glyco-epitopes on human milk oligosaccharides, N-glycans, and O-glycans, overcoming challenges in studying glycan functions due to their structural complexity. The review also highlights applications of GTs in protein glycan editing to probe native glycosylation patterns, remodel antibody glycans for therapeutic purposes, and introduce novel functionalities such as bioorthogonal chemical reporters for bioconjugation. Furthermore, it discusses cellular glyco-engineering strategies using GTs to selectively modify cell-surface glycans for studying biological interactions, enhancing cell therapies, and enabling selective labeling and capture of glycoproteins. The article identifies current limitations and opportunities for expanding the GT toolkit to access a broader range of glyco-epitopes and improve targeted glycan remodeling on proteins and cells.