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.

5-phosphoribosyl 1-pyrophosphate References