Combined oxygen and glucose oscillations distinctly change the transcriptional and physiological state of Escherichia coli

Escherichia coli, a common microbial host for industrial bioproduction, experiences a highly dynamic environment in industrial-scale bioreactors due to significant glucose and oxygen gradients. In this study, we mimic the combined gradients of glucose and oxygen in high-throughput bioreactors to study the transcriptional response of E. coli to industrial-scale conditions. Under oscillating oxygen conditions, E. coli formed less biomass and accumulated the anaerobic by-product acetate. With respect to oxygen-responsive genes, we found that genes of the TCA cycle and of different electron transport chain complexes were differentially expressed. A global analysis of the expression data revealed that oxygen oscillations had caused a transition towards a catabolite-repressed state and upregulation of several stress-related regulatory programs. Interestingly, the transcriptional changes persisted after oxygen limitation stopped. In contrast, the changes we observed due to glucose starvation, such as induction of the stringent response, were primarily transient. Most importantly, we found that effects of combined oxygen and glucose oscillations were distinct from the ones of oxygen and substrate oscillations alone, suggesting an important interplay between the different metabolic regimes in industrial-scale bioreactors.