title: Metabolic flux in both the purine mononucleotide and histidine biosynthetic pathways can influence synthesis of the hydroxymethyl pyrimidine moiety of thiamine in Salmonella enterica.
abstract: Together, the biosyntheses of histidine, purines, and thiamine pyrophosphate (TPP) contain examples of convergent, divergent, and regulatory pathway integration. Mutations in two purine biosynthetic genes (purI and purH) affect TPP biosynthesis due to flux through the purine and histidine pathways. The molecular genetic characterization of purI mutants and their respective pseudorevertants resulted in the conclusion that <1% of the wild-type activity of the PurI enzyme was sufficient for thiamine but not for purine synthesis. The respective pseudorevertants were found to be informational suppressors. In addition, it was shown that accumulation of the purine intermediate aminoimidazole carboxamide ribotide inhibits thiamine synthesis, specifically affecting the conversion of aminoimidazole ribotide to hydroxymethyl pyrimidine.
authors.affiliation: Department of Bacteriology, University of Wisconsin-Madison, Madison 53706, USA.
authors.forename: Shara
authors.initials: S
authors.lastname: Allen
authors.forename: Julie L
authors.initials: JL
authors.lastname: Zilles
authors.forename: Diana M
authors.initials: DM
authors.lastname: Downs
mesh_terms: D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006639:Histidine / Q000096:biosynthesis*; D017354:Point Mutation; D011687:Purines / Q000096:biosynthesis* / Q000737:chemistry; D011743:Pyrimidines / Q000096:biosynthesis; D012265:Ribonucleotides / Q000378:metabolism; D019779:Salmonella enterica / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D013489:Suppression, Genetic; D013831:Thiamine / Q000096:biosynthesis* / Q000737:chemistry; D013835:Thiamine Pyrophosphate / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D011687:Purines; D011743:Pyrimidines; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D006639:Histidine; C031143:AICA ribonucleotide; C030986:pyrimidine; D013835:Thiamine Pyrophosphate; C030985:purine; D013831:Thiamine