Disease relevance of fnr

• In an anaerobic glycerol/trimethylamine N-oxide/fumarate medium, the fnr mutant grew as well as the parental strain, E. coli K12 MG1655, enabling us to reveal the response to oxygen, nitrate, and nitrite in the absence of glucose repression or artifacts because of variations in growth rate [1].
• In enteric bacteria, the expression of many genes encoding various anaerobic electron transfer functions is controlled by FNR, the product of the autoregulated fnr gene [2].
• Actinobacillus pleuropneumoniae hlyX gene homology with the fnr gene of Escherichia coli [3].
• Two-component regulatory proteins ResD-ResE are required for transcriptional activation of fnr upon oxygen limitation in Bacillus subtilis [4].
• Anaerobic control of denitrification in Pseudomonas stutzeri escapes mutagenesis of an fnr-like gene [5].

High impact information on fnr

• We have identified in the narK-fnr intergenic region a promotor activated by anaerobiosis independently of FNR [6].
• Unlike in E.coli, where fnr expression is weakly repressed by anaerobiosis, fnr gene expression in B.subtilis is strongly activated by anaerobiosis [6].
• The Escherichia coli fnr gene product, FNR, is a DNA binding protein that regulates a large family of genes involved in cellular respiration and carbon metabolism during conditions of anaerobic cell growth [7].
• To investigate this process, a fnr mutant that encodes an altered FNR protein with three amino acid substitutions in the N-terminal domain was constructed by site-directed mutagenesis [7].
• Furthermore, similar studies with mutants of nirA and areA control genes and the niaD nitrate reductase structural gene show that crnA expression is mediated by the products of nirA (nitrate induction control gene), areA (nitrogen metabolite repression control gene), and niaD (involved in autoregulation of nitrate reductase) [8].

Chemical compound and disease context of fnr

• The nucleotide sequence of a 1.64 kb fragment of E. coli DNA containing the fnr gene (regulatory gene for fumarate and nitrate reduction) was determined using the dideoxy chain termination method [9].
• Mutations in the Escherichia coli fnr and tgt genes: control of molybdate reductase activity and the cytochrome d complex by fnr [10].
• Regulation of expression of the adhE gene, encoding ethanol oxidoreductase in Escherichia coli: transcription from a downstream promoter and regulation by fnr and RpoS [11].
• RNA was isolated from cultures of Escherichia coli strain MG1655 and derivatives defective in fnr, narXL, or narXL with narP, during aerobic growth, or anaerobic growth in the presence or absence of nitrate or nitrite, in non-repressing media in which both strain MG1655 and an fnr deletion mutant grew at similar rates [12].
• A library of Escherichia coli fnr mutants has been screened to identify FNR (regulator of fumarate and nitrate reduction) variants that are defective repressors, but competent activators [13].

Biological context of fnr

• It was not possible to assign specific metabolic lesions to the fnr mutants nor to the remaining classes, which all exhibited pleiotropic phenotypes [14].
• Succinate dehydrogenase (sdhCDAB) gene expression in Escherichia coli is negatively regulated by the arcA and fnr gene products during anaerobic cell growth conditions [15].
• Nucleotide sequence of the fnr gene and primary structure of the Enr protein of Escherichia coli [9].
• A library of random mutations in the Escherichia coli fnr gene has been screened to identify positive control mutants of FNR that are defective in transcription activation at Class I promoters [16].
• Two distinct regulatory domains have been delineated in the 5' region of the operon which respond respectively to positive induction by the fnr gene product under anaerobic conditions and to positive induction by the narL gene product in the presence of nitrate (S.F. Li, T. Rabi, and J.A. DeMoss, J. Bacteriol. 164:25-32) [17].

Anatomical context of fnr

• Reduced-minus-oxidized difference spectrum analyses of cell membranes confirmed the effect of the fnr gene product on the production of cytochrome d oxidase in the cell [18].
• The nirA gene was overexpressed in Escherichia coli and was shown to be exported to the periplasm [19].

Associations of fnr with chemical compounds

• Introduction of an fnr+ gene into UV14 restored anaerobic repression of sodA::lacZ and restored the ability of the cells to reduce nitrate [20].
• The fnr gene was initially defined by the isolation of some pleiotropic mutants which characteristically lacked the ability to use fumarate and nitrate as reducible substrates for supporting anaerobic growth and several other anaerobic respiratory functions [21].
• The N-terminal sequence of FNR (Mr 30,000) was identical to that predicted from the fnr gene starting with the initiating methionine residue and including a four-cysteine cluster (16)Cys-X3-Cys-X2-Cys-X5-Cys(29) [22].
• The results indicate that lower conversion of pyruvate to acetyl-CoA is the main reason for high fluxes through lactate dehydrogenase (LDH) in cultures of the arcA, fnr double mutant strain [23].
• The results suggest that fnr is involved in anaerobic control of components of the cytochrome d complex and of the redox system that transfers electrons to molybdate [10].

Other interactions of fnr

• Anaerobic, but not aerobic, expression of phi (hmp-lacZ)1 was stimulated three- to four-fold by an fnr mutation; an apparent Fnr-binding site is present in the hmp promoter [24].
• These increases were totally dependent on a functional fnr gene and were shown by S1 mapping experiments to be due to transcriptional read-through from the Fnr-dependent nirB promoter [25].
• The expression of fnr-lacZ was relatively unaffected by iron limitation suggesting that Fnr levels in the cell do not change in response to iron [26].
• LacZ operon fusions were constructed and were inserted in single copies into strain MC4100 and into its fnr, arcA or hemA carrying derivatives [27].
• Expression of narL does not require the fnr gene product, a pleiotropic activator that is required for full expression of narC, frd, and tor [28].

Analytical, diagnostic and therapeutic context of fnr

• After error-prone PCR mutagenesis of the gonococcal fnr gene, we identified four mutant fnr derivatives carrying the same S18F substitution, and we showed that the mutant FNR could activate transcription from a range of class I and class II FNR-dependent promoters in E. coli [29].
• In the same way, using the anti-trimethylamine-N-oxide reductase serum, rocket immunoelectrophoresis analyses were able to show that the inducible apoenzyme is not regulated by the fnr gene product and that molybdate does not seem necessary for the synthesis or stabilisation of this enzyme [30].

References