Mutations in the Tryptophan Operon Allow PurF-Independent Thiamine Synthesis by Altering Flux In Vivo
- 1 February 2008
- journal article
- Published by American Society for Microbiology in Journal of Bacteriology
- Vol. 190 (3) , 815-822
- https://doi.org/10.1128/jb.00582-07
Abstract
Phosphoribosyl amine (PRA) is an intermediate in purine biosynthesis and also required for thiamine biosynthesis in Salmonella enterica . PRA is normally synthesized by phosphoribosyl pyrophosphate amidotransferase, a high-turnover enzyme of the purine biosynthetic pathway encoded by purF . However, PurF-independent PRA synthesis has been observed in strains having different genetic backgrounds and growing under diverse conditions. Genetic analysis has shown that the anthranilate synthase-phosphoribosyltransferase (AS-PRT) enzyme complex, involved in the synthesis of tryptophan, can play a role in the synthesis of PRA. This work describes the in vitro synthesis of PRA in the presence of the purified components of the AS-PRT complex. Results from in vitro assays and in vivo studies indicate that the cellular accumulation of phosphoribosyl anthranilate can result in nonenzymatic PRA formation sufficient for thiamine synthesis. These studies have uncovered a mechanism used by cells to redistribute metabolites to ensure thiamine synthesis and may define a general paradigm of metabolic robustness.Keywords
This publication has 43 references indexed in Scilit:
- PurF-Independent Phosphoribosyl Amine Formation inyjgFMutants ofSalmonella entericaUtilizes the Tryptophan Biosynthetic Enzyme Complex Anthranilate Synthase-PhosphoribosyltransferaseJournal of Bacteriology, 2006
- Anthranilate Synthase Can Generate Sufficient Phosphoribosyl Amine for Thiamine Synthesis in Salmonella entericaJournal of Bacteriology, 2003
- Metabolic Flux in Both the Purine Mononucleotide and Histidine Biosynthetic Pathways Can Influence Synthesis of the Hydroxymethyl Pyrimidine Moiety of Thiamine in Salmonella entericaJournal of Bacteriology, 2002
- Characterization and chemical properties of phosphoribosylamine, an unstable intermediate in the de novo purine biosynthetic pathwayBiochemistry, 1988
- Biosynthesis of thiamin: 5-aminoimidazole ribotide as the precursor of all the carbon atoms of the pyrimidine moietyJournal of the American Chemical Society, 1984
- Limited proteolysis of N-(5′-phosphoribosyl)anthranilate isomerase: Indoleglycerol phosphate synthase from Escherichia coli yields two different enzymically active, functional domainsJournal of Molecular Biology, 1980
- Anthranilate SynthetasePublished by Wiley ,1973
- Purification and Comparison of the N‐(5′‐Phosphoribosyl)anthranilic Acid Isomerase/Indole‐3‐glycerol Phosphate Synthetase of Tryptophan Biosynthesis from Three Species of EnterobacteriaceaeEuropean Journal of Biochemistry, 1970
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970
- Purine biosynthesis: Enzymatic formation of ribosylamine-5-phosphate from ribose-5-phosphate and ammoniaBiochemical and Biophysical Research Communications, 1967