ACS Synth Biol. 2026 Mar 30. doi: 10.1021/acssynbio.5c00740. Online ahead of print.

ABSTRACT

Triterpenoid saponins are widely distributed natural products with diverse pharmacological activities. They are synthesized through the attachment of sugar moieties to the triterpenoid skeleton, a process catalyzed by UDP-glycosyltransferases (UGTs). However, the UGTs responsible for the glycosylation of many triterpenoids remain unidentified, primarily due to the limited understanding of sequence-function relationships. Here, we systematically analyzed and characterized UGTs in Glycyrrhiza glabra, revealing that UGT73F/P enzymes mediate the primary glycosylation of triterpenoids with distinctive regioselectivity. This finding was further supported by a kingdom-wide mining effort and selective characterization among 286 UGT73F/P enzymes from 167 plant species, covering 54 families. In addition, we found that UGT73F and UGT73P enzymes were specific to legume species. Finally, we identified a K-region within the enzyme active site that governs the differentiated function of UGT73F/P enzymes. Our study highlights the great potential of UGT73F/P enzymes for precise triterpenoid glycosylation and expands the enzymatic toolkit for triterpenoid saponin biosynthesis.

PMID:41913442 | DOI:10.1021/acssynbio.5c00740