Effect of fermentation parameters during scale-up on enzyme stability

During scale-up of fermentation process, there are many factors that can impact the fermentation performance and therefore require close attention. Cell growth, mixing, respiration are some of the main factors that need to be balanced across scales so that product concentration, yield and productivity can be maintained at consistent levels. But among such factors that need careful balancing, protein stability was found to be one. A specific protein which had expected production and activity during small scale work showed dramatic loss in activity at successively larger scales, even when all major fermentation parameters were unchanged between scales. This loss of activity was attributed to loss of protein stability and the causes for this impact were explored. The impact of pH, temperature, mixing and aeration on growth of cells, and health of culture, typically is clear and therefore effort is made to keep constant across scales. But the effect of such variables on stability of a single protein among a cocktail of enzymes during scale-up is more subtle. We hypothesize that fermentation parameters in scale-up were impacting the stability of this enzyme, causing a drop in its relative ratio to other proteins. In this case then, we explored ways to adjust these fermentation parameters without compromising overall performance.