Enhancing L-serine production in Corynebacterium glutamicum based on increasing carbon flow from sucrose to L-serine

L-serine is utilized in various applications across the pharmaceutical and food industry. Corynebacterium glutamicum, a non-pathogenic strain, is extensively used in amino acid production. However, the current titer and productivity of L-serine through direct fermentation are insufficient to meet the demands of industrial production. This shortfall arises from the strain’s inadequacy sucrose utilization, which affects both L-serine productivity and sucrose consumption rate. To solve the problem, this research conducted three strategies to increase the carbon flow from sucrose to L-serine. Initially, ALE was performed using a stress of 300 g/L sucrose based on A36-pDSer, and a biosensor-assisted high-throughput screening platform was utilized to identify the mutants with higher intracellular L-serine concentration. The strain A36-mut achieved 39.0 g/L L-serine titer, marking a notable 25.3% improvement over the parent strain A36 (31.1 g/L). Subsequently, the overexpression of the L-serine exporter serE along with its transcription factor serR in strain A36-mut led to an improvement in the L-serine production, reaching 44.8 g/L. Finally, by optimizing the fed-batch fermentation process, the L-serine titer and productivity were improved to 53.7 g/L and 0.50 g/L/h, respectively. This research presented the highest L-serine titer from sucrose in C. glutamicum to date, offering the possibility for the industrialization production of L-serine by fermentation.