Mutations in the tryptophan operon allow PurF-independent thiamine synthesis by altering flux in vivo

J Bacteriol. 2008 Feb;190(3):815-22. doi: 10.1128/JB.00582-07. Epub 2007 Jun 8.


Phosphoribosyl amine (PRA) is an intermediate in purine biosynthesis and also required for thiamine biosynthesis in Salmonella enterica. PRA is normally synthesized by phosphoribosyl pyrophosphate amidotransferase, a high-turnover enzyme of the purine biosynthetic pathway encoded by purF. However, PurF-independent PRA synthesis has been observed in strains having different genetic backgrounds and growing under diverse conditions. Genetic analysis has shown that the anthranilate synthase-phosphoribosyltransferase (AS-PRT) enzyme complex, involved in the synthesis of tryptophan, can play a role in the synthesis of PRA. This work describes the in vitro synthesis of PRA in the presence of the purified components of the AS-PRT complex. Results from in vitro assays and in vivo studies indicate that the cellular accumulation of phosphoribosyl anthranilate can result in nonenzymatic PRA formation sufficient for thiamine synthesis. These studies have uncovered a mechanism used by cells to redistribute metabolites to ensure thiamine synthesis and may define a general paradigm of metabolic robustness.

Publication types

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

MeSH terms

  • Anthranilate Phosphoribosyltransferase / chemistry
  • Anthranilate Phosphoribosyltransferase / genetics
  • Anthranilate Phosphoribosyltransferase / metabolism
  • Anthranilate Synthase / chemistry
  • Anthranilate Synthase / genetics
  • Anthranilate Synthase / metabolism
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Culture Media
  • Models, Molecular
  • Mutation*
  • Operon*
  • Ribosemonophosphates / metabolism*
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / growth & development
  • Salmonella typhimurium / metabolism*
  • Thiamine / metabolism*
  • Tryptophan / metabolism*
  • ortho-Aminobenzoates / metabolism


  • Bacterial Proteins
  • Culture Media
  • Ribosemonophosphates
  • ortho-Aminobenzoates
  • anthranilic acid
  • phosphoribosylamine
  • Tryptophan
  • Anthranilate Phosphoribosyltransferase
  • Anthranilate Synthase
  • Thiamine