Functional characterization and substrate promiscuity analysis of UDP-glucose dehydrogenases from licorice (Glycyrrhiza uralensis)

Abstract

Uridine diphosphate glucose dehydrogenase (UGDH) has a crucial role in the synthesis of UDP-glucuronic acid (UDPGA), which is the important sugar donor in the glucuronosylation of bioactive triterpene saponins in the traditional Chinese medicine Glycyrrhiza uralensis Fisch. UGDHs usually exist as isoforms in plants, but knowledge of their unique binding sites and patterns remains largely incomplete. Here, we mined five UGDH isoforms in G. uralensis transcriptome that catalyze the oxidation of UDP-glucose (UDPG) to UDPGA and had different catalytic efficiencies. Molecular modeling and molecular dynamics simulation revealed the potential catalytic residues for the catalytic efficiencies of the isoforms. Moreover, the UGDH isoforms exhibited substrate promiscuity by catalyzing two structurally diverse UDPG derivatives, which was further demonstrated by docking studies. This work gives new insights into the UGDH isoforms involved in the biosynthesis of glucuronides in G. uralensis, and extends the understanding of the versatility of UGDHs.