Insights into Enzymes Involved in the Biosynthesis of Protopanaxadiol-Type Ginsenosides in Panax Species.

Protopanaxadiol (PPD)-type ginsenosides, as the primary bioactive components of Panax medicinal plants, have become a research hotspot in natural products due to their diverse pharmacological activities. The biosynthetic pathway of PPD-type ginsenosides in Panax species and the related enzymes is becoming increasingly clear. However, for most enzymes, research has been largely limited to identifying their functions in the pathway, with insufficient exploration of their biochemical properties, structures, and mechanisms. This review, from the perspective of enzymatic catalysis, systematically elucidates the biosynthetic pathway of PPD-type ginsenosides in Panax species. It focuses on the functions, sequence, and biochemical features of the enzymes and uses homology modeling and AlphaFold predictions to generate testable hypotheses regarding their structures and catalytic mechanisms, while also summarizing directed evolution strategies, aiming to provide a theoretical foundation for the construction of in vitro or microbial "cell factories" and to promote the efficient synthesis and application of highly bioactive PPD-type ginsenosides.