Natural products of pentacyclic triterpenoids: from discovery to heterologous biosynthesis

cytochrome P450 monooxygenases (CYP450s) and glycosyltransferases (GTs). Many biosynthetic pathways of triterpenoid saponins have been elucidated by studying their metabolic regulation network through the use of multiomics and identifying their functional genes. Unfortunately, natural resources of pentacyclic triterpenoids are limited due to their low content in plant tissues and the long growth cycle of plants. Based on the understanding of their biosynthetic pathway and transcriptional regulation, plant bioreactors and microbial cell factories are emerging as alternative means for the synthesis of desired triterpenoid saponins. The rapid development of synthetic biology, metabolic engineering, and fermentation technology has broadened channels for the accumulation of pentacyclic triterpenoid saponins. In this review, we summarize the classification, distribution, structural characteristics, and bioactivity of pentacyclic triterpenoids. We further discuss the biosynthetic pathways of pentacyclic triterpenoids and involved transcriptional regulation. Moreover, the recent progress and characteristics of heterologous biosynthesis in plants and microbial cell factories are discussed comparatively. Finally, we propose potential strategies to improve the accumulation of triterpenoid saponins, thereby providing a guide for their future biomanufacturing.