Metabolic Engineering of Corynebacterium glutamicum for Efficient l-Homoserine Production from Lignocellulose-Derived Sugars

l-Homoserine, a nonproteinogenic amino acid, is a promising platform for synthesizing various compounds. Microbial fermentation holds great potential for large-scale l-homoserine production, yet it still faces challenges, such as low yields. Here, we aimed to develop an efficient Corynebacterium glutamicum chassis for high-level l-homoserine production by optimizing the co-utilization of lignocellulose-derived sugars. Co-utilization of mixed sugars was achieved by rewiring the glucose and xylose metabolic pathways, engineering transporter capabilities, and implementing β-glucosidase-secreting strategies. Finally, the resulting strain produced 93.1 g/L l-homoserine in a fed-batch bioreactor with a yield of 0.41 g/g from mixed sugars and a productivity of 1.29 g/L/h. This represents the highest titer and productivity of l-homoserine reported to date for C. glutamicum. Overall, these results underscore the potential of C. glutamicum as a robust chassis for efficient l-homoserine production from simulated lignocellulose-derived sugars, further reinforcing its established role in the industrial-scale biosynthesis of amino acids.