Model-based process development for a continuous lactic acid bacteria fermentation

A mechanistic process model describing a lactic acid bacteria (LAB) fermentation was applied to develop a continuous fermentation process. Producing LAB for the dairy industry in a continuous cultivation, which would allow harvesting the cells during the cultivation, would reduce production costs compared to traditional batch processes.

To this end, a validated mechanistic model of a Streptococcus thermophilus fermentation was used for a model-based continuous process evaluation. The fermentation model consists of biological and chemical mechanisms including a description of the growth rate as a function of pH and inhibition effects of metabolites.

The optimal dilution rate and substrate concentration in the feed were estimated in order to maximize the cell yield (biomass concentration) and to minimize the waste of substrate during the continuous fermentation in a 50 m3 bioreactor for two scenarios: downstream capabilities are i) flexible, and ii) fixed.

The biomass concentration is restricted by the growth-inhibiting lactic acid concentration, which is produced by the growing bacteria. Furthermore, the substrate, which is supplied by the feed, should be consumed completely in the fermentation and not wasted in the bioreactor effluent owing to raw material costs.

The resulting non-linear optimization problem was formulated and solved in MATLAB®. A Monte Carlo simulation showed the robustness of the results, where a biomass concentration of 5 g L-1 could be achieved in the continuous fermentation with a substrate wastage of less than 3 % in the bioreactor effluent.

The productivity of the continuous process was similar to a traditional batch process, but frequent cleaning and sterilization are no longer necessary in a continuous process resulting in a shorter unproductive downtime of the bioreactors. This promising potential of a continuous process for LAB cultivations encourages pilot-scale studies for a comprehensive techno-economic evaluation.