Synthetic biomanufacturing of triterpenoids: From laboratory to industry

Triterpenoids are important natural secondary metabolites with diverse bioactivities, including antioxidant, anti-inflammatory, and anti-cancer properties, making them valuable for applications in the pharmaceutical, cosmetic, and food industries. Currently, triterpenoids are mainly obtained through natural extraction or chemical synthesis. However, these conventional approaches are often limited by production efficiency, environmental burdens, and product diversity. Rapid advances in metabolic engineering and synthetic biology have promoted the emergence of heterologous biosynthesis as a promising, efficient, and sustainable strategy for triterpenoids production. In this review, we first summarize the classification and bioactive properties of triterpenoids, together with the challenges and potential solutions associated with their microbial synthesis. Then, we analyze the key characteristics of microbial hosts and their corresponding biosynthetic pathways for triterpenoids production, aiming to establish programmable platforms that overcome the limitations of natural biosynthesis. Subsequently, we propose metabolic engineering and synthetic biology strategies, including enzyme optimization, pathway optimization, compartmentalization engineering, and systems biology approaches, for optimizing matter and energy transmission and thereby enhancing triterpenoids production. We further discuss the potential challenges for scaling up triterpenoids production from laboratory-scale studies to industrial-scale applications, including the optimization of large-scale fermentation process and the improvement of downstream extraction and recovery. Finally, we discuss the techno-economic feasibility and industrial prospects of microbial triterpenoid production, highlight current regulation and governance in synthetic biology related to triterpenoids biosynthesis, analyze existing limitations, and propose potential solutions to provide insights for future research on the biomanufacturing of triterpenoids.