Modular engineering of aromatic metabolism in Corynebacterium glutamicum enables protocatechuic acid and gallic acid production

Protocatechuic acid (PCA) and gallic acid (GA) are valuable phenolic compounds with diverse pharmacological activities, including antioxidant and antitumor properties, and have broad applications in the food, cosmetic, chemical, and pharmaceutical industries. However, the industrial production of these compounds remains limited by the insufficient performance of current microbial cell factories, resulting in low productivity and high manufacturing costs. Here, an efficient biosynthetic platform based on Corynebacterium glutamicum was systematically established for the production of PCA and GA. Through reconstruction of the PCA biosynthetic pathway, elimination of competing branches in the shikimate pathway, enhancement of the key rate-limiting enzyme, and modulation of the glucose uptake system to increase phosphoenolpyruvate supply, metabolic flux was effectively redirected toward PCA accumulation, resulting in the engineered strain PCA16 achieving a PCA titer of 19.8 g/L in shake-flask fermentation. Building on this platform, GA biosynthesis was established by introducing a mutant pobA from Pseudomonas aeruginosa and further strengthening the shikimate pathway, enabling strain GA06 to produce 7.86 g/L GA in shake-flask fermentation. Upon scale-up in a 5 L bioreactor, GA production was further increased to 25.66 g/L, representing the highest reported titer for GA production using C. glutamicum to date. Overall, this work demonstrates the strong potential of C. glutamicum as a robust microbial chassis for efficient production of PCA and GA, and provides a versatile platform for the biosynthesis of PCA-derived aromatic compounds.