High yield strategies for triterpenoid biosynthesis in cell factories

Triterpenoids are natural products widely found in the plant kingdom and have various pharmacological effects such as anti-inflammatory, antioxidant and anti-tumour. However, the content of triterpenoids in medicinal plants is low, and it is difficult to purify and isolate them due to their complex structure. The efficient production of some triterpenoids in chassis organisms has been achieved by constructing a heterologous triterpenoid synthesis pathway in engineered strains such as yeast, modifying the key enzymes in the pathway, and adjusting the metabolism of yeast. Modification of key enzymes in the synthetic pathway is currently an effective strategy to enhance the heterologous synthesis of triterpenoids. This paper reviews the current research progress on the modification of key enzymes downstream in the synthetic pathway and the design of key enzymes around them to enhance triterpenoid production in five main areas: 1) increasing the supply of triterpenoid precursors; 2) inhibition of the natural sterol pathway; 3) fusion expression of related enzymes; 4) compartmentalisation of the metabolic pathway; and 5) tapping and enhancing the triterpenoid efflux pump. Finally, recent advances and applications of artificial intelligence (AI) in enzyme engineering and pathway design for triterpenoid biosynthesis are highlighted. Challenges and perspectives for further increasing the yield of triterpenoid synthesis in Saccharomyces cerevisiae are presented.