Evidence for a new, oxygen-regulated biosynthetic pathway for the pyrimidine moiety of thiamine in Salmonella typhimurium

Abstract

The synthesis of the pyrimidine moiety of thiamine (vitamin B1) shares five reactions with the de novo purine biosynthetic pathway. Aminoimidazole ribotide (AIR) is the last common intermediate before the two pathways diverge. Evidence for the existence of a new pathway to the pyrimidine which bypasses the de novo purine biosynthetic pathway is reported here. This pathway is only expressed under anaerobic growth conditions and is denoted alternative pyrimidine biosynthesis or APB. Labeling studies are consistent with pantothenate being a precursor to the pyrimidine moiety of thiamine that is synthesized by the APB pathway. The APB pathway is independent of the alternative purF function which was proposed previously (D. M. Downs and J. R. Roth, J. Bacteriol. 173:6597-6604, 1991). The alternative purF function is shown here to be affected by temperature and exogenous pantothenate. Although the evidence suggests that the APB pathway is separate from the alternative purF function, the relationship between this function and the APB pathway is not yet clear.

Discovery of a SAR11 growth requirement for thiamin’s pyrimidine precursor and its distribution in the Sargasso Sea

“…P. ubique lacks the ability to synthesize HMP through NMT1 activity, histidine þ vitamin B 6 did not alleviate thiamin-limited growth (Supplementary Figure S7). Thiamin-limited growth was not relieved by pantothenate or THZ addition (Supplementary Figure S7) as has been reported previously for other organisms (Droop, 1958;Downs, 1992).…”

ApbA, the Ketopantoate Reductase Enzyme of Salmonella typhimurium Is Required for the Synthesis of Thiamine via the Alternative Pyrimidine Biosynthetic Pathway

“…Genetic data presented elsewhere shows that contrary to earlier mapping data, apbA is the locus previously designated panE. 2 The symbol of apbA has been retained to reflect the involvement of this enzyme in thiamine biosynthesis. KPA reductase activities have been identified and characterized to different extents in Saccharomyces cerevisiae, Escherichia coli, and Pseudomonas maltophilia 845 (6,7).…”

“…Recent efforts to define the in vivo function for ApbA were led by the observation that pantothenate, as well as thiamine, could correct the nutritional requirement of an apbA mutant. 2 Further experiments indicated that under conditions where apbA mutants required thiamine, the pantoic acid moiety of pantothenate was sufficient to restore growth. 2 Because of the putative oxidoreductase activity of ApbA, we focused on the step in pantoic acid synthesis that involved the reduction of ketopantoic acid (KPA) (Fig.…”

“…The alternative pyrimidine biosynthetic (APB) 1 pathway allows synthesis of thiamine in Salmonella typhimurium in the absence of de novo purine biosynthesis (1,2). The apbA gene was the first genetic locus found to be required for function of the APB pathway (3).…”

The YggX Protein of Salmonella enterica Is Involved in Fe(II) Trafficking and Minimizes the DNA Damage Caused by Hydroxyl Radicals

“…The method for transduction and subsequent purification of transductants has been previously described (24). Isogenic strains were constructed with standard genetic techniques utilizing linked markers.…”