The roles of glycosyltransferases in shaping flavonoid diversity in plants.

Covering: up to 2026Flavonoids belong to one of the largest families of specialized metabolites in plants and play pivotal roles in plant adaptation and human health. In their biosynthesis, the formation of core aromatic structures is followed by various chemical modifications that further decorate these scaffolds, shaping their chemical diversity, biological functions, and physicochemical properties. Among these modifications, glycosylation is the most prevalent, transferring monosaccharides from activated nucleotide sugars to acceptor molecules to form glycosidic bonds. This reaction is catalyzed by UDP-glycosyltransferases (UGTs), a class of enzymes that generate structurally diverse glycosides from a relatively limited set of flavonoid core structures. Through these catalytic processes, UGTs have driven the structural and functional diversification of flavonoids across plant lineages. This review highlights the structure, biochemistry, and phylogeny of UGTs participating in flavonoid biosynthesis. We discuss how substrate promiscuity, together with broad specificity toward both sugar donors and acceptor substrates, allows UGTs to expand flavonoid chemical diversity. Additional focus is placed on how UGT gene expression is integrated into tissue-specific and stress-responsive regulatory networks that shape flavonoid diversity, and how UGT-dependent glycosylation plays a critical role in the stabilization and subcellular sequestration of diverse flavonoids. Lastly, we highlight emerging strategies for engineering plant flavonoid UGTs and glycosylation pathways, including the opportunities and limitations of computational and artificial intelligence-assisted approaches.