Improving succinic acid production by tuning polysulfides metabolism in Yarrowia lipolytica.

BACKGROUD: Succinic acid (SA) is a significant C4-dicarboxylic acid with broad applications in the food, chemical, and pharmaceutical industries. In microbial SA production, Yarrowia lipolytica shows great potential. Polysulfides are vital for maintaining redox balance and cellular health in yeast. RESULTS: In this study, we changed the polysulfides metabolism of Y. lipolytica to enhance SA production. The 3-mercaptopyruvate sulfurtransferase (3-MST) and rhodanese (RHOD) encoding genes were disrupted in Y. lipolytica PGC01003, which led to increased biomass and SA production. In a 3-L scale bioreactor, the mutant strain produced 64.5 g/L SA, representing a 37.8% increase compared with PGC01003. Further investigations indicated that the number of mitochondria was decreased, but the ATP production and oxygen consumption rate were increased in the mutant strain. Transcriptomic analysis indicated that apoptosis genes were downregulated, and cell cycle related genes were upregulated. CONCLUSIONS: This study demonstrated that polysulfides affected the overall growth and metabolism of Y. lipolytica. The same strategy may have the potential to be applied in improving other cell factories.