Involvement of the relA gene product and feedback inhibition in the regulation of DUP-N-acetylmuramyl-peptide synthesis in Escherichia coli.
The regulation of uridine diphosphate-N-acetylmuramyl-peptide (UDP-MurNAc-peptide) synthesis was studied by labeling Escherichia coli strains auxotrophic for lysine and diaminopimelate with [3H]diaminopimelate for 15 min under various conditions. The amounts of [3H]diaminopimelate incorporated into UDP-MurNAc-tripeptide and -pentapeptide by a stringent (rel+) strain were the same in the presence or absence of lysine. Chloramphenicol-treated rel+ cells showed a 2.8-fold increase in labeled UDP-MurNAc-pentapeptide. An isogenic relaxed (relA) strain deprived of lysine showed a 2.7-fold increase in UDP-MurNAc-pentapeptide. Thus, UDP-MurNAc-pentapeptide synthesis is regulated by the relA gene. D-Cycloserine treatment of rel+ and relA strains caused a depletion of intracellular UDP-MurNAc-pentapeptide. Labeled UDP-MurNAc-tripeptide accumulated in D-cycloserine-treated cells of the rel+ and relA strains, suggesting that UDP-MurNAc-pentapeptide is a feedback inhibitor of UDP-MurNAc-peptide synthesis. In lysine-deprived cells, D-cycloserine treatment caused 41- and 71-fold accumulations of UDP-MurNAc-tripeptide in rel+ and relA strains, respectively. A 124-fold increase in UDP-MurNAc-tripeptide occurred in lysine-deprived rel+ cells treated with both chloramphenicol and D-cycloserine. These results indicate that both the relA gene product and feedback inhibition are involved in regulating UDP-MurNAc-peptide synthesis during amino acid deprivation.
D002701:Chloramphenicol / Q000494:pharmacology; D003523:Cycloserine / Q000494:pharmacology; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D005796:Genes; D008239:Lysine / Q000494:pharmacology; D009842:Oligopeptides / Q000096:biosynthesis*; D010457:Peptidoglycan / Q000096:biosynthesis; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives; D014539:Uridine Diphosphate Sugars / Q000031:analogs & derivatives
D009842:Oligopeptides; D010457:Peptidoglycan; D014538:Uridine Diphosphate N-Acetylmuramic Acid; D014539:Uridine Diphosphate Sugars; C002225:UDP-N-acetylmuramic acid pentapeptide; D002701:Chloramphenicol; D003523:Cycloserine; D008239:Lysine