Enhancing cytidine biosynthesis by coupling minicell-forming morphology with biofilm-based fermentation

Cytidine is an important nucleoside in the pharmaceutical and biotechnology fields. To improve its biosynthesis efficiency, this study proposes a strategy that integrates minicell-forming recombinant strains with biofilm-based fermentation. By knocking out the key gene minC that regulates cell division, a cytidine-producing strain capable of stable minicell formation was constructed. In the biofilm-based fermentation system, the cytidine titer of this strain reached 1.74 g/L, representing a 114% increase compared to traditional free-cell fermentation. The study further revealed that minicell formation may promote biofilm formation, which in turn helps mitigate acidification during the fermentation process. This work provides a new approach for the synergistic optimization of morphology engineering and fermentation processes in microbial cytidine production, with significant potential in industrial biotechnology.