Minimizing acetate formation from overflow metabolism in : comparison of genetic engineering strategies to improve robustness toward sugar gradients in large-scale fermentation processes.

, a well characterized workhorse in biotechnology, has been used to produce many recombinant proteins and metabolites, but have a major drawback in its tendency to revert to overflow metabolism. This phenomenon occurs when excess sugar triggers the production of mainly acetate under aerobic conditions, a detrimental by-product that reduces carbon efficiency, increases cell maintenance, and ultimately inhibits growth. Although this can be prevented by controlled feeding of the sugar carbon source to limit its availability, gradients in commercial-scale bioreactors can still induce it in otherwise carbon-limited cells.

Impact of Elevated Levels of Dissolved CO on Performance and Proteome Response of an Industrial 2'-Fucosyllactose Producing Strain.

Large-scale microbial industrial fermentations have significantly higher absolute pressure and dissolved CO concentrations than otherwise comparable laboratory-scale processes. Yet the effect of increased dissolved CO (dCO) levels is rarely addressed in the literature. In the current work, we have investigated the impact of industrial levels of dCO (measured as the partial pressure of CO, pCO) in an -based fed-batch process producing the human milk oligosaccharide 2'-fucosyllactose (2'-FL).