UGT708 glycosyltransferases: Nature's architects of C-glycosides

Uridine Diphosphate glycosyltransferases (UGTs) catalyze the transfer of glycosyl moieties from donors to acceptors, a modification critical for plant growth, development, and metabolic homeostasis. These enzymes are ubiquitous across all life domains, playing key roles in the biosynthesis of diverse glycosides. This review focuses on the plant UGT708 family, which is uniquely characterized by its ability to form stable C-glycosidic bonds on flavonoid backbones, enhancing metabolic stability and bioactivity. We conducted a comprehensive analysis of UGT distribution and functional evolution across life forms, highlighting their evolutionary significance and diversification. Emphasizing plant-specific adaptations, UGT708 enzymes specialize in C-glycosylation of flavonoid, polyphenolic compounds, diketones and aromatic hydrocarbons, particularly 2-hydroxyflavanones and polyhydroxy ketones, facilitating the production of defense metabolites such as schaftosides and isoschaftosides which enhance plant resilience to environmental stresses. Clade-specific variations in the conserved PSPG motif, notably in monocots, correlate with differences in sugar-donor specificity and substrate promiscuity, reflecting structural and functional diversity within the family. Structural analyses reveal key active site residues responsible for selective C-glycosylation, resulting in a broad spectrum of glycosides with ecological and therapeutic importance. While UGT708s hold great promise as biocatalysts for generating bioactive compounds, more detailed studies on their molecular interactions and catalytic mechanisms are essential to fully exploit their potential in agriculture, medicine, and industry.