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Mutations in apbC (mrp) prevent function of the alternative pyrimidine biosynthetic pathway in Salmonella typhimurium
1Department of Bacteriology, University of Wisconsin--Madison, 53706, USA.
Abstract:
The alternative pyrimidine biosynthetic (APB) pathway can synthesize the 4-amino-5-hydroxymethyl-2-methyl pyrimidine (HMP) moiety of thiamine in Salmonella typhimurium independently of de novo purine biosynthesis. When mutants defective in function of the APB pathway were isolated, the predominant class (40%) were defective in a single locus we have designated apbC. Mutations in apbC block function of the APB pathway since they prevent growth of a purF mutant in the absence of thiamine. Lesions in apbC also cause a thiamine auxotrophy in strains proficient in purine biosynthesis when fructose is provided as the sole carbon and energy source. Results presented here are consistent with ApbC being involved in the conversion of aminoimidazole ribonucleotide to HMP, and we suggest that ApbC performs a redundant step in thiamine synthesis. Sequence analysis demonstrated that apbC mutations were alleles of mrp, a locus previously reported in Escherichia coli as a metG-related protein. We propose that this locus in S. typhimurium be designated apbC to reflect its involvement in thiamine synthesis.
Insights
The alternative pyrimidine biosynthetic pathway in Salmonella typhimurium synthesizes thiamine. A newly identified gene, apbC, is crucial for this process, acting in the conversion of aminoimidazole ribonucleotide to HMP.
Area of Science:
- Microbiology
- Biochemistry
- Molecular Biology
Background:
- The alternative pyrimidine biosynthetic (APB) pathway synthesizes the HMP moiety of thiamine in Salmonella typhimurium.
- This pathway operates independently of de novo purine biosynthesis.
Purpose of the Study:
- To identify and characterize genes involved in the APB pathway.
- To elucidate the function of the newly identified apbC gene in thiamine synthesis.
Main Methods:
- Isolation and characterization of APB pathway mutants.
- Genetic analysis of apbC mutations.
- Sequence analysis of the apbC locus.
Main Results:
- A predominant class of mutants (40%) were defective in a single locus, designated apbC.
- apbC mutations block APB pathway function and cause thiamine auxotrophy.
- Sequence analysis revealed apbC mutations are alleles of the mrp locus.
Conclusions:
- ApbC is involved in the conversion of aminoimidazole ribonucleotide to HMP.
- ApbC likely performs a redundant step in thiamine synthesis.
- The mrp locus in S. typhimurium should be designated apbC due to its role in thiamine synthesis.