A simple yet efficient fed-batch strategy, dual-point pH-stat (DPPS), was developed for the culture of recombinant Escherichia coli TG1 expressing ToxA5.1, a single domain antibody neutralizing Clostridium difficile toxin A. Cell densities up to 26.6 g DCW/L were achieved with the newly proposed fed-batch strategy. This strategy has shown the potential of enabling high cell density culture of E. coli by providing indirect feedback control over feeding of a solution containing glucose and other macronutrients.