Scale-down studies for the scale-up of a recombinant Corynebacterium glutamicum fed-batch fermentation: loss of homogeneity leads to lower levels of cadaverine production

BACKGROUND: The loss of efficiency and performance of bioprocesses on scale-up is well known, but not fully understood. This work addresses this problem, by studying the effect of some fermentation gradients (pH, glucose and oxygen) that occur at the larger scale in a bench-scale two-compartment reactor [plug flow reactor (PFR) + stirred tank reactor (STR)] using the cadaverine-producing recombinant Corynebacterium glutamicum DM1945 Δact3 Ptuf-ldcC_OPT. The new scale-down strategy developed here studied the effect of increasing the magnitude of fermentation gradients by considering not only the average cell residence time in the PFR (τ_PFR), but also the mean frequency at which the bacterial cells entered the PFR (f_m) section of the two-compartment reactor. RESULTS: On implementing this strategy the cadaverine production decreased on average by 26%, 49% and 59% when the τ_PFR was increased from 1 to 2 min and then 5 min respectively compared to the control fermentation. The carbon dioxide productivity was highest (3.1-fold that of the control) at a τ_PFR of 5 min, but no losses were observed in biomass production. However, the population of viable but non-culturable cells increased as the magnitude of fermentation gradients was increased. The new scale-down approach was also shown to have a bigger impact on fermentation performance than the traditional one. CONCLUSION: This study demonstrated that C. glutamicum DM1945 Δact3 Ptuf-ldcC_OPT physiological response was a function of the magnitude of fermentation gradients simulated. The adaptations of a bacterial cell within a heterogeneous environment ultimately result in losses in fermentation productivity as observed here.