Metabolic engineering and high-cell-density fermentation of Corynebacterium glutamicum to improve isopropanol production.

Isopropanol is a major chemical used in the chemical industry as a chemical intermediate, organic solvent, and hand sanitizer. In this study, engineered Corynebacterium glutamicum strains capable of high-cell-density fermentation were developed to efficiently produce isopropanol. Transcriptome analysis identified genes that showed significant expression changes under high-cell-density fermentation condition. Based on this analysis, metabolic pathways involved in fermentation byproducts were inhibited, leading to improved isopropanol production under high-cell-density fermentation. To address the metabolic imbalance caused by this metabolic redesign, a glycolysis bypass was introduced, which improved glucose consumption and isopropanol production. High-cell-density fed-batch fermentation under an optimal condition achieved a production titer of 30.66 ± 1.24 g/L, a yield of 0.53 ± 0.03 mol/mol, and a productivity of 511.08 ± 20.72 mg/L/h, representing the highest isopropanol production in C. glutamicum. The development of this strain capable of high-cell-density fermentation demonstrates great potential for the industrial production of isopropanol.