THIAMINE PYROPHOSPHATE (TPP) NEGATIVELY REGULATES TRANSCRIPTION OF SOME THI GENES OF SALMONELLA-TYPHIMURIUM

In Salmonella typhimurium, thiamine is a required nutrient that is syn thesized de novo. Labeling studies have demonstrated probable precurso rs for both the 4-amino-5-hydroxymethyl-2-methylpyrimidine pyrophospha te moiety and the 4-methyl-5-(beta-hydroxyethyl) thiazole monophosphat e moiety. The isolation of thiamine auxotrophs with mutations in at le ast five different genetic loci is reported. The majority (22 of 25) o f the mutants required only the thiazole moiety of thiamine to satisfy their growth requirement. Most (14 of 25) of the mutants were affecte d in the thi cluster at min 90 on the S. typhimurium genetic map. Data provided herein indicate that this cluster encodes an operon whose tr anscription is regulated by thiamine and suggest that thiamine pyropho sphate, or a molecule derived form it, is the effector molecule. Mutan ts with altered regulation of this operon were isolated, and we propos e that they are defective in thiamine phosphate kinase, the product of the thiL gene.