Metabolic engineering of Yarrowia lipolytica for heterologous oleanolic acid production

Oleanolic acid (OA) is a pentacyclic triterpenoid known for its biological properties such as antioxidation activity. Herein, we developed an efficient biosynthetic pathway for OA production in Yarrowia lipolytica. The engineered strain, YL-OA0, produced 16.3 mg/L of OA, and the production efficiency was further increased by 5.65-fold to 92.1 mg/L following overexpression of the key genes involved in the mevalonate (MVA) pathway. Transcriptomic and metabolomic analyses demonstrated the increase in the percentage of unsaturated fatty acids. The electron transfer of the strain YL-OA7 was restricted. Therefore, we fused the gene encoding cytochrome P450 (CYP716A12) to that encoding NADPH-P450 reductase; this resulted in an increase in the OA yield to 129.9 mg/L in the strain YL-fuOA1. The strain YL-fuOA1 could produce 540.7 mg/L OA in fed-batch fermentation in a 5 L fermenter. This study shows the feasibility of the production of high value triterpenoid compounds using Y. lipolytica as a platform.