P67: Inhibitory effect of ammonium ion during an E. coli fermentation process

Over the past two decades, the fermentation of E. coli has been routinely used for the production of recombinant products.  E. coli has been the primary choice for fermentation processes due to its ease of growth and its simple nutritional requirements.  Unbalanced nutritional consumption rates, overfeeding, and the addition of acid/base reagents can cause the accumulation of undesirable substances in fermentation broth.  One such substance is the ammonium ion.  Previous work has shown that although ammonia can be used as a nitrogen source and is metabolically assimilated by E. coli, at critical levels, ammonium can also inhibit cell growth. In addition, ammonia can inhibit gene expression and recombinant protein production. The objective of this study has been the investigation of the levels of the ammonium ion in E. coli culture medium that can cause growth inhibition and reduction in therapeutic recombinant protein production. The correlation between cell growth, protein production and ammonium ion concentration of the medium will be presented.