Analyzing the metabolic stress response of recombinant Escherichia coli cultures expressing human interferon beta in high cell density fed batch cultures using time course transcriptomic data

Over expression of recombinant proteins is known to cause a metabolic burden to the host cells which leads to down regulation of both growth rates and protein expression. Most studies in this regard have been conducted in low density shake flask cultures which does not capture the essential features of an industrial scale bioprocess. In the present work we studied the transcriptomic profiling at different specific growth rates while expressing the recombinant human interferon beta in fed batch cultures with complex media. These conditions mimicked the industrial fermentations for recombinant proteins. To determine the transcriptomic response of E.coli BL21(DE3) to recombinant protein production at three different specific growth rates, samples were collected for four time points (0h, 2h, 4h, 6h) post induction for the fed batch cultivations at specific growth rates 0.2h-1, 0.3h-1, 0.4h-1 respectively and induced at an optical density of 30. 0h (uninduced) sample was taken as control conditions for every run.