Analysis of ThiC variants in the context of the metabolic network of Salmonella enterica

J Bacteriol. 2012 Nov;194(22):6088-95. doi: 10.1128/JB.01361-12. Epub 2012 Sep 7.


In bacteria, the 4-amino-hydroxymethyl-2-methylpyrimidine (HMP) moiety of thiamine is synthesized from 5-aminoimidazole ribotide (AIR), a branch point metabolite of purine and thiamine biosynthesis. ThiC is a member of the radical S-adenosylmethionine (AdoMet) superfamily and catalyzes the complex chemical rearrangement of AIR to HMP-P. As reconstituted in vitro, the ThiC reaction requires AdoMet, AIR, and reductant. This study analyzed variants of ThiC in vivo and in vitro to probe the metabolic network surrounding AIR in Salmonella enterica. Several variants of ThiC that required metabolic perturbations to function in vivo were biochemically characterized in vitro. Results presented herein indicate that the subtleties of the metabolic network have not been captured in the current reconstitution of the ThiC reaction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Gene Expression Regulation, Bacterial / physiology*
  • Genetic Variation*
  • Methionine
  • Molecular Sequence Data
  • Molecular Structure
  • Mutation
  • Pantothenic Acid / metabolism
  • Salmonella typhimurium / metabolism*
  • Thiamine / biosynthesis
  • Thiamine / chemistry


  • Bacterial Proteins
  • ThiC protein, Bacteria
  • Pantothenic Acid
  • Methionine
  • Thiamine