Compartmentalizing metabolic pathway in Candida glabrata for acetoin production

Acetoin, a valuable compound, has high potential as a biochemical building block. In this study, subcellular metabolic engineering was applied to engineer the mitochondrion of Candida glabrata for acetoin production. With the aid of mitochondrial targeting sequences, a heterologous acetoin pathway was targeted into the mitochondria to increase the enzyme concentrations and level of intermediate, followed by coupling with the mitochondrial pyruvate carrier (MPC) to increase the availability of mitochondrial pyruvate. As a result, the strain comprising the combination of the mitochondrial pathway and MPC could yield approximately 3.26 g/L of acetoin, which was about 59.8% higher than that produced by the cytoplasmic pathway. These results provided a new insight into the metabolic engineering of C. glabrata for acetoin production, and offered a potential platform to improve the performance of engineered pathways.