Abstract
Metabolite profiling of E. coli W3110 and the isogenic ΔrelA mutant cells was used to characterize the RelA-dependent stringent control of metabolism under different growth conditions. Metabolic profiles were obtained by gas chromatography–mass spectrometry (GC-MS) analysis and revealed significant differences between E. coli strains grown at different conditions. Major differences between the two strains were assessed in the levels of amino acids and fatty acids and their precursor metabolites, especially when growing at the lower dilution rates, demonstrating differences in their metabolic behavior. Despite the fatty acid biosynthesis being the most affected due to the lack of the RelA activity, other metabolic pathways involving succinate, lactate and threonine were also affected. Overall, metabolite profiles indicate that under nutrient-limiting conditions the RelA-dependent stringent response may be elicited and promotes key changes in the E. coli metabolism.
Highlights
Bacteria are often used as microbial cell factories for delivering functional biomolecules with industrial or pharmaceutical interest
Recombinant bioprocesses can be quite demanding for microbial cells due to the metabolic burden caused by the depletion of central metabolites like amino acids toward recombinant protein synthesis, which unbalances most central metabolic activities resulting in considerable productivity losses
The synthesis of ppGpp has been mainly associated with cellular responses to amino acid starvation, which in E. coli are mainly initiated by the activation of the ribosome-associated enzyme encoded by the relA gene catalyzing the conversion of cellular GDP into ppGpp [7], recent studies have indicated that this molecule accumulates during carbon starvation [8,9,10]
Summary
Bacteria are often used as microbial cell factories for delivering functional biomolecules with industrial or pharmaceutical interest. A second ppGpp synthetase, i.e., the bifunctional enzyme SpoT that has both hydrolase and synthetase activities, has been described to be involved in ppGpp accumulation during carbon starvation [11,12], but its activity was shown to be much weaker than the one of the RelA enzyme [13]. This suggests that RelA may be central in the response to carbon starvation. It was suggested that these two nutritional stress phenomena are strictly correlated, the exhaustion of carbon often resulting in a rapid decrease in amino acids availability, entangling the activity of both enzymes [8]
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