High hydrogen peroxide concentration in the feed-zone affects bioreactor cell productivity with liquid phase oxygen supply strategy

Abstract

Liquid phase oxygen supply strategy (LPOS), in which hydrogen peroxide (H(2)O(2)) is used to supply oxygen to the bioreactor, leads to low cell productivity despite high specific productivities of relevant metabolites. We hypothesized that high H(2)O(2) concentrations in the feed-zone led to local cell death, which in turn, lead to lower cell productivity. To test the hypothesis, a mathematical model was developed. Bacillus subtilis 168 was used as the model system in this study. The model simulations of cell concentrations in the bioreactor-zone were verified with the experimental results. The feed-zone H(2)O(2) concentrations remained 12-14 times higher than bulk bioreactor concentrations. The high local concentrations are expected to cause local cell killing, which explains the decrease in overall cell production by 50% at 300 rpm compared to conventional cultivation. Further, among the four different feed strategies studied using the model, dissolved oxygen (DO) controlled H(2)O(2) feed strategy caused least local cell killing and improved overall cell production by 34%.