Conserved pyridoxal protein that regulates Ile and Val metabolism

J Bacteriol. 2013 Dec;195(24):5439-49. doi: 10.1128/JB.00593-13. Epub 2013 Oct 4.


Escherichia coli YggS is a member of the highly conserved uncharacterized protein family that binds pyridoxal 5'-phosphate (PLP). To assist with the functional assignment of the YggS family, in vivo and in vitro analyses were performed using a yggS-deficient E. coli strain (ΔyggS) and a purified form of YggS, respectively. In the stationary phase, the ΔyggS strain exhibited a completely different intracellular pool of amino acids and produced a significant amount of l-Val in the culture medium. The log-phase ΔyggS strain accumulated 2-ketobutyrate, its aminated compound 2-aminobutyrate, and, to a lesser extent, l-Val. It also exhibited a 1.3- to 2.6-fold increase in the levels of Ile and Val metabolic enzymes. The fact that similar phenotypes were induced in wild-type E. coli by the exogenous addition of 2-ketobutyrate and 2-aminobutyrate indicates that the 2 compounds contribute to the ΔyggS phenotypes. We showed that the initial cause of the keto acid imbalance was the reduced availability of coenzyme A (CoA); supplementation with pantothenate, which is a CoA precursor, fully reversed phenotypes conferred by the yggS mutation. The plasmid-borne expression of YggS and orthologs from Bacillus subtilis, Saccharomyces cerevisiae, and humans fully rescued the ΔyggS phenotypes. Expression of a mutant YggS lacking PLP-binding ability, however, did not reverse the ΔyggS phenotypes. These results demonstrate for the first time that YggS controls Ile and Val metabolism by modulating 2-ketobutyrate and CoA availability. Its function depends on PLP, and it is highly conserved in a wide range species, from bacteria to humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacillus subtilis / genetics
  • Butyrates / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / isolation & purification
  • Carrier Proteins / metabolism*
  • Coenzyme A / metabolism
  • Escherichia coli / enzymology*
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / isolation & purification
  • Escherichia coli Proteins / metabolism*
  • Gene Deletion
  • Genetic Complementation Test
  • Isoleucine / metabolism*
  • Protein Binding
  • Pyridoxal Phosphate / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Valine / metabolism*


  • Butyrates
  • Carrier Proteins
  • Escherichia coli Proteins
  • YggS protein, E coli
  • Isoleucine
  • Pyridoxal Phosphate
  • alpha-ketobutyric acid
  • Valine
  • Coenzyme A