[Metabolic engineering of Corynebacterium glutamicum for glutaric acid production]

Glutaric acid is an important monomer for the synthesis of polymeric materials such as polyesters and polyamides, whereas its bio-based production efficiency has long been limited. In this study, we focused on the key metabolic bottlenecks in glutaric acid biosynthesis and constructed a high-producing Corynebacterium glutamicum cell factory. First, the glutaric acid biosynthetic pathway was integrated into the genome of a high-lysine-producing C. glutamicum strain to establish a basal production strain. Subsequently, modular metabolic engineering strategies were employed to strengthen the biosynthetic modules and eliminate byproduct formation pathways, resulting in a glutaric acid titer of 78.67 g/L. To alleviate α-ketoglutarate depletion, a cofactor regeneration cycle composed of l-glutamate oxidase and catalase was introduced, further increasing the glutaric acid titer to 84.43 g/L. Finally, pH and temperature were optimized in a 5 L bioreactor, leading to a final glutaric acid titer of 97.63 g/L with a yield of 0.36 g/g. This study lays a foundation for the construction of high-producing glutaric acid cell factories based on C. glutamicum.