Engineering Critical Enzymes and Pathways for Improved Triterpenoid Biosynthesis in Yeast

Triterpenoids represent a diverse group of phytochemicals that are widely distributed in the plant kingdom and have many biological activities. The heterologous production of triterpenoids in Saccharomyces cerevisiae has been successfully implemented by introducing various triterpenoid biosynthetic pathways. By engineering related enzymes as well as through yeast metabolism, the yield of various triterpenoids is significantly improved from the milligram per liter scale to the gram per liter scale. This achievement demonstrates that engineering critical enzymes is considered a potential strategy to overcome the main hurdles of the industrial application of these potent natural products. Here, we review strategies for designing enzymes to improve the yield of triterpenoids in S. cerevisiae in terms of three main aspects: 1, elevating the supply of the precursor 2,3-oxidosqualene; 2, optimizing triterpenoid-involved reactions; and 3, lowering the competition of the native sterol pathway. Then, we provide challenges and prospects for further enhancing triterpenoid production in S. cerevisiae.