Aminoimidazole Carboxamide Ribotide Exerts Opposing Effects on Thiamine Synthesis in Salmonella enterica

J Bacteriol. 2015 Sep;197(17):2821-30. doi: 10.1128/JB.00282-15. Epub 2015 Jun 22.


In Salmonella enterica, the thiamine biosynthetic intermediate 5-aminoimidazole ribotide (AIR) can be synthesized de novo independently of the early purine biosynthetic reactions. This secondary route to AIR synthesis is dependent on (i) 5-amino-4-imidazolecarboxamide ribotide (AICAR) accumulation, (ii) a functional phosphoribosylaminoimidazole-succinocarboxamide (SAICAR) synthetase (PurC; EC, and (iii) methionine and lysine in the growth medium. Studies presented here show that AICAR is a direct precursor to AIR in vivo. PurC-dependent conversion of AICAR to AIR was recreated in vitro. Physiological studies showed that exogenous nutrients (e.g., methionine and lysine) antagonize the inhibitory effects of AICAR on the ThiC reaction and decreased the cellular thiamine requirement. Finally, genetic results identified multiple loci that impacted the effect of AICAR on thiamine synthesis and implicated cellular aspartate levels in AICAR-dependent AIR synthesis. Together, the data here clarify the mechanism that allows conditional growth of a strain lacking the first five biosynthetic enzymes, and they provide additional insights into the complexity of the metabolic network and its plasticity.

Importance: In bacteria, the pyrimidine moiety of thiamine is derived from aminoimidazole ribotide (AIR), an intermediate in purine biosynthesis. A previous study described conditions under which AIR synthesis is independent of purine biosynthesis. This work is an extension of that previous study and describes a new synthetic pathway to thiamine that depends on a novel thiamine precursor and a secondary activity of the biosynthetic enzyme PurC. These findings provide mechanistic details of redundancy in the synthesis of a metabolite that is essential for nucleotide and coenzyme biosynthesis. Metabolic modifications that allow the new pathway to function or enhance it are also described.

Publication types

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

MeSH terms

  • Aminoimidazole Carboxamide / analogs & derivatives*
  • Aminoimidazole Carboxamide / chemistry
  • Aminoimidazole Carboxamide / metabolism
  • Aspartate Aminotransferases / genetics
  • Aspartate Aminotransferases / metabolism
  • Bacterial Proteins / metabolism
  • Gene Expression Regulation, Bacterial / physiology*
  • Lysine / metabolism
  • Methionine / metabolism
  • Molecular Structure
  • Mutation
  • Peptide Synthases / chemistry
  • Peptide Synthases / metabolism*
  • Purine-Nucleoside Phosphorylase / genetics
  • Purine-Nucleoside Phosphorylase / metabolism
  • Ribonucleotides / chemistry
  • Ribonucleotides / metabolism*
  • Salmonella enterica / genetics
  • Salmonella enterica / metabolism*
  • Thiamine / biosynthesis*


  • Bacterial Proteins
  • Ribonucleotides
  • aminoimidazole ribotide
  • Aminoimidazole Carboxamide
  • Methionine
  • Purine-Nucleoside Phosphorylase
  • 5'-methylthioadenosine phosphorylase
  • Aspartate Aminotransferases
  • Peptide Synthases
  • PurC protein, Bacteria
  • phosphoribosylaminoimidazole-succinocarboxamide synthetase
  • AICA ribonucleotide
  • Lysine
  • Thiamine