Biosynthesis and Biotransformation of Plant Triterpenoids: Current Advances and Future Perspectives.

Abstract

Plant triterpenoids, including tetracyclic and pentacyclic triterpene saponins, represent a large and structurally diverse class of natural products with broad pharmacological activities such as anti-inflammatory, antitumor, hepatoprotective, and immunomodulatory effects. These compounds are widely used in pharmacy and food industries. However, their production relies largely on plant extraction, which is associated with low yield, long cultivation cycles, and environmental pollution. In contrast, microbial biosynthesis offers a sustainable and environmentally friendly approach. In recent years, synthetic biology has greatly accelerated the development of microbial cell factories for triterpenoid production. This review provides a comprehensive overview of the biosynthetic pathways of plant triterpenoids. We also systematically summarize the key enzyme families involved, including oxidosqualene cyclases (OSCs), cytochrome P450 monooxygenases (P450s), and UDP-glycosyltransferases (UGTs), with emphasis on the diversity of their activities and substrate specificities. We further discuss the structural diversity and bioactivity of representative tetracyclic and pentacyclic triterpenoids, such as ginsenosides, licorice triterpenoids, mogrosides, saikosaponins, and lupeol-type triterpenoids. To address the challenges of low productivity in microbial cell factories, we reviewed current challenges and corresponding strategies for efficient triterpenoid biosynthesis in engineered microbial hosts, particularly Saccharomyces cerevisiae. These strategies include metabolic flux rewiring, pathway compartmentalization and cytotoxicity alleviation. Finally, this review outlines future directions in the field, with a focus on how artificial intelligence (AI) can accelerate pathway elucidation, engineering of heterologous enzyme and microbial chassis, and process optimization, paving the way toward cost-effective, eco-friendly, and sustainable production of plant triterpenoids.