Enhanced protocatechuic acid production using metabolically engineered Corynebacterium glutamicum

Protocatechuate acid (PCA) is a phenolic acid naturally synthesized by various microorganisms. To enhance PCA production during fermentation using Corynebacterium glutamicum , a statistical optimization of the production medium was performed using full factorial design, the steepest ascent method, and the response surface method. The optimized production medium enabled PCA production of over 5 g/L in a 72-h batch culture. PCA cytotoxicity affected strain growth and PCA production rate, with an inhibitory concentration of approximately 5 g/L in the fermentation broth. Finally, continuous fermentation was operated for 150 h in steady-state mode, maintaining the concentration of PCA below 5 g/L. The optimization method established in this study successfully increased PCA production levels, and the findings presented herein are anticipated to contribute to the industrialization of PCA production using C. glutamicum.