The post-transcriptional regulatory system CSR controls the balance of metabolic pools in upper glycolysis ofEscherichia coli

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Abstract

Summary

Metabolic control inEscherichia coliis a complex process involving multilevel regulatory systems but the involvement of post-transcriptional regulation is uncertain. The post-transcriptional factor CsrA is stated as being the only regulator essential for the use of glycolytic substrates. A dozen enzymes in the central carbon metabolism (CCM) have been reported as potentially controlled by CsrA, but its impact on the CCM functioning has not been demonstrated. Here, a multiscale analysis was performed in a wild-type strain and its isogenic mutant attenuated for CsrA (including growth parameters, gene expression levels, metabolite pools, abundance of enzymes and fluxes). Data integration and regulation analysis showed a coordinated control of the expression of glycolytic enzymes. This also revealed the imbalance of metabolite pools in thecsrAmutant upper glycolysis, before the phosphofructokinase PfkA step. This imbalance is associated with a glucose–phosphate stress. Restoring PfkA activity in thecsrAmutant strain suppressed this stress and increased the mutant growth rate on glucose. Thus, the carbon storage regulator system is essential for the effective functioning of the upper glycolysis mainly through its control of PfkA. This work demonstrates the pivotal role of post-transcriptional regulation to shape the carbon metabolism.

This work demonstrated the pivotal role of post-transcriptional regulation to shape the E. coli carbon metabolism. The CSR system was shown here to be essential for the effective functioning of the upper glycolysis mainly through its control of PfkA.

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