title: A novel activity for fungal nitronate monooxygenase: detoxification of the metabolic inhibitor propionate-3-nitronate.
abstract: Nitronate monooxygenase (NMO; E.C. 1.13.12.16) oxidizes alkyl nitronates to aldehydes and nitrite. Although the biochemistry of the enzyme from fungal sources has been studied extensively, the physiological role is unknown. The ability of NMO to detoxify propionate-3-nitronate was tested by measuring growth of recombinant Escherichia coli containing the gene encoding for the enzyme in either the absence or presence of the nitronate and its conjugate acid 3-nitropropionate. The mixture propionate-3-nitronate/3-nitropropionate is toxic to E. coli cells lacking expression of NMO, but the toxicity is overcome through either induction of the gene for NMO or through addition of exogenous enzyme to the cultures. Both Williopsis saturnus and Neurospora crassa were able to grow in the presence of 0.4mM propionate-3-nitronate and 19.6mM 3-nitropropionate, while a knockout mutant of N. crassa lacking NMO was inhibited by concentrations of propionate-3-nitronate and 3-nitropropionate >0.3 and 600μM, respectively. These results strongly support the conclusion that NMO functions to protect the fungi from the environmental occurrence of the metabolic toxin.
authors.affiliation: Department of Chemistry, Georgia State University, Atlanta, GA 30302-409, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Francis
authors.forename: Shirley F
authors.initials: SF
authors.lastname: Nishino
authors.forename: Jim C
authors.initials: JC
authors.lastname: Spain
authors.forename: Giovanni
authors.initials: G
authors.lastname: Gadda
mesh_terms: D000963:Antimetabolites / Q000378:metabolism* / Q000633:toxicity; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D055786:Gene Knockout Techniques; D005800:Genes, Fungal; D007700:Kinetics; D050216:Metabolic Detoxication, Phase I; D009492:Neurospora crassa / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D009574:Nitro Compounds / Q000378:metabolism* / Q000633:toxicity; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D011422:Propionates / Q000378:metabolism* / Q000633:toxicity; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D013481:Superoxides / Q000378:metabolism; D055320:Williopsis / Q000201:enzymology / Q000235:genetics
chemical_list: D000963:Antimetabolites; D005656:Fungal Proteins; D009574:Nitro Compounds; D011422:Propionates; D011994:Recombinant Proteins; D013481:Superoxides; D010088:Oxidoreductases; C053917:propionate-3-nitronate oxidase; C015392:3-nitropropionic acid