Overcoming acetate in Escherichia coli recombinant protein fermentations

Minimizing acetate formation in E. coli fermentations

“…In addition to a loss of carbon and therefore an economic sink, acetate is also detrimental to recombinant protein production and inhibits cell growth [2]. For more information about overcoming acetate in E. coli recombinant protein fermentations see reference [3].…”

“…A culture of E. coli will generate acetate when the cells surpass a threshold specific rate of glucose consumption, regardless of the availability of oxygen to the culture [3]. In the literature, several specific fermentation strategies are mentioned to reduce acetate production [1,[16][17][18][19][20].…”

“…Another approach to hold the growth rate below the threshold for acetate production, is the pH-stat, where a nutrient feed is activated when the pH increases and variants, where the culture is dosed with more nutrient than necessary. However a fundamental drawback of the pH-stat is that it detects starvation rather than the acetate threshold directly [3]. In general, a consequence of limiting the growth rate is that biomass is generated at a slower rate than the cells are capable of achieving.…”

High Yield Production of Heterologous Proteins with Escherichia coli

“…Inhibition of acetate is significant for cells cultured in a defined medium than a complex medium. Inhibitory effect of acetic acid on growth of E. coli cells affecting the volumetric productivity of recombinant proteins during high cell density fermentation has been widely documented 1,[26][27] . Acetate is produced when E. coli is grown under anaerobic or oxygen-limiting conditions; however, E. coli cultures growing in the presence of excess glucose can also produce acetate even under aerobic conditions.…”

“…Exponential feeding is widely used so that the cells can be grown at the desired specific growth rate, preventing the formation of toxic byproducts like acetate [24][25][26][27] . The feeding method to maintain the desired specific growth rate is fairly simple and amenable to feed-forward control using substrate balance equations 28 .…”