A novel pH-stat fed-batch strategy to boost the production of nicotinamide mononucleotide by high cell density fermentation

Nicotinamide mononucleotide (NMN), a naturally occurring nucleotide with various biological activities, has recently attracted significant interest for its potential applications in pharmaceutical and nutraceutical products. In this study, a genetically engineered E. coli via pH-stat fed batch fermentation produced a high concentration of intracellular NMN. The production process involved pH-stat glucose feeding and continuous feeding of nicotinamide (NAM). Various cumulative NAM concentrations of 6.4, 8.4, 10.4, and 14 g/L produced NMN of 16.7, 21.2, 22.5, and 10.7 g/L, respectively. Furthermore, the highest intracellular NMN concentration of 22.5 g/L was produced with 10.4 g/L of total cumulative NAM concentration along with a productivity of 1.13 g/L/h. This is the highest intracellular NMN titer and productivity achieved through optimized fed-batch fermentation to date. This also demonstrates that a high cell density approach through pH-stat feeding offers the potential to produce high quality, substantial NMN at a reasonable cost.