Advances in UDP-Glycosyltransferases from Medicinal Plants: Discovery, Catalytic Mechanism, Engineering and Biosynthetic Application.

Glycosylation is a critical structural modification that shapes the pharmacological properties of bioactive ingredients from Traditional Chinese Medicine (TCM), and UDP-glycosyltransferases (UGTs) are the core rate-limiting biocatalysts mediating this process. Traditional plant extraction methods are constrained by resource scarcity, long growth cycles, low target content and high environmental costs, which cannot meet the large-scale industrial demand for high-value medicinal glycosides. This review systematically outlines the latest global advances in medicinal plant UGT research, covering family classification and physiological functions, multi-omics and AI-assisted gene mining, molecular basis of substrate recognition and catalytic specificity, protein engineering for performance optimization, and the construction of full-spectrum biomanufacturing systems including in vitro multi-enzyme cascades, microbial cell factories and plant suspension cell cultures. We further discuss the core challenges of industrial scale-up, regulatory compliance and clinical translation, as well as the significant economic and technical advantages of synthetic biology-based UGT biomanufacturing platforms. This work provides a complete technical framework for the engineering application of medicinal plant UGTs, to support the green and scalable production of rare natural therapeutic glycosides.