ABSTRACT
The initial adaptive transcriptional response to nitrogen (N) starvation in Escherichia coli involves large-scale alterations to the transcriptome mediated by the transcription activator, NtrC. One of the NtrC-activated genes is yeaG, which encodes a conserved bacterial kinase. Although it is known that YeaG is required for optimal survival under sustained N starvation, the molecular basis by which YeaG benefits N starved E. coli remains elusive. By combining transcriptomics with targeted metabolomics analyses, we demonstrate that the methionine biosynthesis pathway becomes transcriptionally dysregulated in ΔyeaG bacteria experiencing sustained N starvation. This results in the aberrant and energetically costly biosynthesis of methionine and associated metabolites under sustained N starvation with detrimental consequences to cell viability. It appears the activity of the master transcriptional repressor of methionine biosynthesis genes, MetJ, is compromised in ΔyeaG bacteria under sustained N starvation, resulting in transcriptional derepression of MetJ-regulated genes. The results suggest that YeaG is a novel regulatory factor and functions as a molecular brake in the transcriptional control of both the NtrC-regulon and methionine biosynthesis genes in E. coli experiencing sustained N starvation.