A role for a conserved kinase in the transcriptional control of methionine biosynthesis inEscherichia coliexperiencing sustained nitrogen starvation
ABSTRACTThe initial adaptive transcriptional response to nitrogen (N) starvation inEscherichia coliinvolves large-scale alterations to the transcriptome mediated by the transcription activator, NtrC. One of the NtrC-activated genes isyeaG, 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 starvedE. coliremains elusive. By combining transcriptomics with targeted metabolomics analyses, we demonstrate that the methionine biosynthesis pathway becomes transcriptionally dysregulated inΔyeaGbacteria 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 inΔyeaGbacteria 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 inE. coliexperiencing sustained N starvation.