From gene discovery to synthetic biology: recent advances in the biosynthesis of oleanane-type pentacyclic triterpenoids

Covering: 2010 to January 2026Oleanane-type pentacyclic triterpenoids (OPTs) represent a prominent class of plant-derived natural products, widely recognized for their potent pharmacological properties, including anticancer, anti-inflammatory, and antidiabetic effects. Although they have significant therapeutic potential, their production is limited by their low natural abundance, intricate biosynthetic pathways, and complex regulatory mechanisms. Recent advances have substantially improved our understanding of the biosynthesis of OPTs, particularly focusing on the elucidation of key enzymes, such as β-amyrin synthases (β-ASs), cytochrome P450 monooxygenases (CYP450s), and UDP-glycosyltransferases (UGTs). Sophisticated transcriptional regulation of OPT biosynthesis is achieved through diverse transcription factors (TFs), which integrate signals from hormonal elicitors, environmental stimuli, and metabolic feedback. Additionally, microRNAs (miRNAs) have emerged as pivotal post-transcriptional regulators, adding another dimension to the complex regulatory networks influencing OPT production. Modern approaches integrating genomics, transcriptomics, proteomics, metabolomics, and advanced computational tools have facilitated the discovery and functional characterization of novel genes and pathways, enabling targeted metabolic engineering strategies. Moreover, recent developments in synthetic biology, including heterologous expression platforms in microbial and plant hosts and innovative genome-editing techniques, offer powerful tools to overcome the current production bottlenecks of OPTs. The integration of artificial intelligence (AI) and machine learning (ML) into OPT research promises a paradigm shift from empirical trial-and-error methods to predictive optimization, facilitating the systematic discovery of biosynthetic gene clusters, rational engineering of key enzymes, and pathway optimization to unlock sustainable and high-yield production of OPTs. This review summarizes the recent advancements in biosynthetic gene discovery, regulatory mechanisms, and synthetic biology strategies for enhancing the OPT production, highlighting future opportunities for the sustainable and scalable production of these valuable natural compounds.