Chemogenomic approach identified yeast YLR143W as diphthamide synthetase Academic Article uri icon


MeSH Major

  • Biosynthetic Pathways
  • Carbon-Nitrogen Ligases
  • Genomics
  • Histidine
  • Ligases
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins


  • Many genes are of unknown functions in any sequenced genome. A combination of chemical and genetic perturbations has been used to investigate gene functions. Here we present a case that such "chemogenomics" information can be effectively used to identify missing genes in a defined biological pathway. In particular, we identified the previously unknown enzyme diphthamide synthetase for the last step of diphthamide biosynthesis. We found that yeast protein YLR143W is the diphthamide synthetase catalyzing the last amidation step using ammonium and ATP. Diphthamide synthetase is evolutionarily conserved in eukaryotes. The previously uncharacterized human gene ATPBD4 is the ortholog of yeast YLR143W and fully rescues the deletion of YLR143W in yeast.

publication date

  • December 4, 2012



  • Academic Article



  • eng

PubMed Central ID

  • PMC3523822

Digital Object Identifier (DOI)

  • 10.1073/pnas.1214346109

PubMed ID

  • 23169644

Additional Document Info

start page

  • 19983

end page

  • 7


  • 109


  • 49