Prenylated phenolic glycosides, such as nodakenin, represent a class of natural products with diverse bioactivities. Their metabolic engineering production remains largely unexplored, primarily due to the scarcity of efficient UDP-glycosyltransferases (UGTs) capable of catalyzing prenylated phenolic substrates. In this study, we characterized several UGT93 enzymes from Angelica decursiva that catalyzed the glycosylation of nodakenetin. Enzymatic assays revealed a pronounced catalytic preference of these enzymes toward various types of prenylated phenolic substrates. Notably, this substrate preference is conserved across UGT93s from other species and a reconstructed ancestral enzyme. Structural analysis and mutation experiments revealed that the preference was caused by the substrate binding with several hydrophobic and aromatic residues. This study highlights the biocatalytic potential of the UGT93 family enzymes, offering promising biocatalysts for the glycosylation of plant-derived prenylated phenolics.
Li et al. (2026) studied this question.