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Pathway Description
5-phosphoribosyl 1-pyrophosphate
Bacillus subtilis (strain 168)
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2025-04-01
Last Updated: 2025-05-08
The 5-phosphoribosyl 1-pyrophosphate (PRPP) effector pathway is a central metabolic route responsible for the de novo biosynthesis of purine nucleotides (AMP and GMP), which are essential for DNA, RNA, energy metabolism, and cellular signaling. This pathway is tightly regulated by PurR, a purine-responsive transcriptional repressor.
PurR senses intracellular purine levels and represses the expression of purine biosynthesis genes when purines are abundant. When purine levels are low, PurR repression is relieved, allowing the transcription of genes necessary for building purines from basic metabolic precursors, with PRPP as the starting substrate.
In response to a signal of excess adenine, represses the transcription of the pur operon, which encodes enzymes of the purine biosynthetic pathway.
Key genes in the PurR regulog include:
Core de novo purine biosynthesis genes:
purF – Encodes amidophosphoribosyltransferase, catalyzing the first committed step of the pathway: the conversion of PRPP to phosphoribosylamine.
purD – Encodes GAR synthetase, catalyzing the formation of glycinamide ribonucleotide (GAR).
purN – Encodes GAR transformylase, which converts GAR to formyl-GAR.
purL, purQ, purS – These form a multi-subunit enzyme complex (FGAM synthetase) that converts formyl-GAR to formylglycinamidine ribonucleotide (FGAM).
purM – Encodes AIR synthetase, catalyzing the formation of aminoimidazole ribonucleotide (AIR).
purE – Encodes N5-CAIR mutase, converting AIR into carboxyaminoimidazole ribonucleotide (CAIR).
purK – Encodes N5-CAIR synthetase, functioning upstream of purE in CAIR formation.
purC – Encodes SAICAR synthetase, catalyzing the conversion of CAIR to SAICAR.
purB – Encodes adenylosuccinate lyase, which participates in two reactions: conversion of SAICAR to AICAR and of adenylosuccinate to AMP.
purH – Encodes a bifunctional enzyme with AICAR transformylase and IMP cyclohydrolase activities, catalyzing the final steps in IMP (inosine monophosphate) synthesis.
Downstream conversion of IMP:
purA – Encodes adenylosuccinate synthetase, converting IMP to AMP.
guaC – Encodes GMP reductase, contributing to purine interconversion and balance between AMP and GMP pools.
Accessory genes:
fhs – Encodes formyltetrahydrofolate synthetase, which generates the one-carbon donor (10-formyl-THF) required for GAR and AICAR formylation steps.
LGG_02640 – Likely encodes a gene co-expressed with purine biosynthetic genes, possibly involved in folate metabolism or regulation.
References
5-phosphoribosyl 1-pyrophosphate References
Jendresen CB, Dimitrov P, Gautier L, Liu M, Martinussen J, Kilstrup M: Towards in vivo regulon kinetics: PurR activation by 5-phosphoribosyl-alpha-1-pyrophosphate during purine depletion in Lactococcus lactis. Microbiology (Reading). 2014 Jul;160(Pt 7):1321-1331. doi: 10.1099/mic.0.077933-0. Epub 2014 Apr 10.
Pubmed: 24722907
Weng M, Zalkin H: Mutations in the Bacillus subtilis purine repressor that perturb PRPP effector function in vitro and in vivo. Curr Microbiol. 2000 Jul;41(1):56-9. doi: 10.1007/s002840010091.
Pubmed: 10919400
Morar M, Anand R, Hoskins AA, Stubbe J, Ealick SE: Complexed structures of formylglycinamide ribonucleotide amidotransferase from Thermotoga maritima describe a novel ATP binding protein superfamily. Biochemistry. 2006 Dec 19;45(50):14880-95. doi: 10.1021/bi061591u.
Pubmed: 17154526
Saxild HH, Brunstedt K, Nielsen KI, Jarmer H, Nygaard P: Definition of the Bacillus subtilis PurR operator using genetic and bioinformatic tools and expansion of the PurR regulon with glyA, guaC, pbuG, xpt-pbuX, yqhZ-folD, and pbuO. J Bacteriol. 2001 Nov;183(21):6175-83. doi: 10.1128/JB.183.21.6175-6183.2001.
Pubmed: 11591660
Anderson BW, Schumacher MA, Yang J, Turdiev A, Turdiev H, Schroeder JW, He Q, Lee VT, Brennan RG, Wang JD: The nucleotide messenger (p)ppGpp is an anti-inducer of the purine synthesis transcription regulator PurR in Bacillus. Nucleic Acids Res. 2022 Jan 25;50(2):847-866. doi: 10.1093/nar/gkab1281.
Pubmed: 34967415
Cossart P, Gicquel-Sanzey B: Cloning and sequence of the crp gene of Escherichia coli K 12. Nucleic Acids Res. 1982 Feb 25;10(4):1363-78. doi: 10.1093/nar/10.4.1363.
Pubmed: 6280141
Aiba H, Fujimoto S, Ozaki N: Molecular cloning and nucleotide sequencing of the gene for E. coli cAMP receptor protein. Nucleic Acids Res. 1982 Feb 25;10(4):1345-61. doi: 10.1093/nar/10.4.1345.
Pubmed: 6280140
Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y: The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453-62. doi: 10.1126/science.277.5331.1453.
Pubmed: 9278503
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