Promiscuous yet specific: a methionine-aromatics interaction drives the reaction scope of the family 1 glycosyltransferase GmUGT88E3 from soybean.

Family 1 glycosyltransferases (GT1s, UGTs) catalyze the regioselective glycosylation of natural products in a single step. We identified GmUGT88E3 as a particularly promising biocatalyst, able to produce a variety of pure, single glycosidic products from polyphenols with high chemical yields. We investigated this particularly desirable duality towards specificity, i.e., promiscuous towards acceptors while regiospecific. Using high-field NMR, kinetic characterization, molecular dynamics simulations and mutagenesis studies, we uncovered that the main molecular determinant of GmUGT88E3 specificity is a methionine-aromatic bridge, an interaction often present in protein structures but never reported for enzyme-substrate interactions.