A connection between iron-sulfur cluster metabolism and the biosynthesis of 4-amino-5-hydroxymethyl-2-methylpyrimidine pyrophosphate in Salmonella enterica

Microbiology (Reading). 2006 Aug;152(Pt 8):2345-2353. doi: 10.1099/mic.0.28926-0.


Several cellular pathways have been identified which affect the efficiency of thiamine biosynthesis in Salmonella enterica. Mutants defective in iron-sulfur (Fe-S) cluster metabolism are less efficient at synthesis of the pyrimidine moiety of thiamine. These mutants are compromised for the conversion of aminoimidazole ribotide (AIR) to 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate (HMP-P), not the synthesis of AIR. The gene product ThiC contains potential ligands for an Fe-S cluster that are required for function in vivo. The conversion of AIR to HMP-P is sensitive to oxidative stress, and variants of ThiC have been identified that have increased sensitivity to oxidative growth conditions. The data are consistent with ThiC or an as-yet-unidentified protein involved in HMP-P synthesis containing an Fe-S cluster required for its physiological function.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / physiology
  • Iron-Sulfur Proteins / metabolism*
  • Paraquat / pharmacology
  • Pyrimidines / biosynthesis*
  • Ribonucleotides / metabolism
  • Salmonella enterica / metabolism*
  • Superoxides / metabolism
  • Thiamine / metabolism


  • 4-amino-5-hydroxymethyl-2-methylpyrimidine
  • Bacterial Proteins
  • Iron-Sulfur Proteins
  • Pyrimidines
  • Ribonucleotides
  • ThiC protein, Bacteria
  • Superoxides
  • aminoimidazole ribotide
  • Paraquat
  • Thiamine