Escherichia coli NsrR regulates a pathway for the oxidation of 3-nitrotyramine to 4-hydroxy-3-nitrophenylacetate.
Chromatin immunoprecipitation and microarray (ChIP-chip) analysis showed that the nitric oxide (NO)-sensitive repressor NsrR from Escherichia coli binds in vivo to the promoters of the tynA and feaB genes. These genes encode the first two enzymes of a pathway that is required for the catabolism of phenylethylamine (PEA) and its hydroxylated derivatives tyramine and dopamine. Deletion of nsrR caused small increases in the activities of the tynA and feaB promoters in cultures grown on PEA. Overexpression of nsrR severely retarded growth on PEA and caused a marked repression of the tynA and feaB promoters. Both the growth defect and the promoter repression were reversed in the presence of a source of NO. These results are consistent with NsrR mediating repression of the tynA and feaB genes by binding (in an NO-sensitive fashion) to the sites identified by ChIP-chip. E. coli was shown to use 3-nitrotyramine as a nitrogen source for growth, conditions which partially induce the tynA and feaB promoters. Mutation of tynA (but not feaB) prevented growth on 3-nitrotyramine. Growth yields, mutant phenotypes, and analyses of culture supernatants suggested that 3-nitrotyramine is oxidized to 4-hydroxy-3-nitrophenylacetate, with growth occurring at the expense of the amino group of 3-nitrotyramine. Accordingly, enzyme assays showed that 3-nitrotyramine and its oxidation product (4-hydroxy-3-nitrophenylacetaldehyde) could be oxidized by the enzymes encoded by tynA and feaB, respectively. The results suggest that an additional physiological role of the PEA catabolic pathway is to metabolize nitroaromatic compounds that may accumulate in cells exposed to NO.
Rankin
Linda D
LD
Department of Molecular and Cell Biology, the University of Texas at Dallas, 800 W Campbell Road, Richardson, TX 75080, USA.
Bodenmiller
Diane M
DM
Partridge
Jonathan D
JD
Nishino
Shirley F
SF
Spain
Jim C
JC
Spiro
Stephen
S
D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology; D009596:Nitrophenols / Q000378:metabolism*; D010084:Oxidation-Reduction; D010627:Phenethylamines / Q000378:metabolism; D010648:Phenylacetates / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014439:Tyramine / Q000031:analogs & derivatives* / Q000378:metabolism
C531304:3-nitrotyramine; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D009596:Nitrophenols; C529899:NsrR protein, E coli; D010627:Phenethylamines; D010648:Phenylacetates; D014157:Transcription Factors; C026242:4-hydroxy-5-nitrophenyl acetic acid; D009569:Nitric Oxide; D014439:Tyramine