Bacterial metabolism of 5-aminosalicylic acid. Initial ring cleavage.
The metabolism of 5-aminosalicylate (5AS) by a bacterial strain, Pseudomonas sp. BN9, was studied. Intact cells of Pseudomonas sp. BN9 grown with 5AS oxidized 5AS and 2,5-dihydroxybenzoate (gentisate), whereas cells grown with gentisate oxidized only the growth substrate of all substituted salicylates tested. Cell extracts from Pseudomonas sp. BN9 catalysed the stoichiometric reaction of 1 mol of oxygen with 1 mol of 5AS to a metabolite with an intense u.v.-absorption maximum at 352 nm (pH 8.0). This metabolite was accumulated under neutral conditions, but was rapidly destroyed at acid pH. It was identified by m.s. and acid-catalysed deamination to fumarylpyruvate (trans-2,4-dioxohept-5-enedioic acid) as cis-4-amino-6-carboxy-2-oxohexa-3,5-dienoate, thus demonstrating direct cleavage of the monohydroxylated substrate 5AS to a non-aromatic ring-fission product. The enzyme responsible for conversion of 5AS was shown to be Fe(II)-dependent and to be distinct from gentisate 1,2-dioxygenase in strain BN9.
Stolz
A
A
Institut für Mikrobiologie, Universität Stuttgart, Federal Republic of Germany.
Nörtemann
B
B
Knackmuss
H J
HJ
D000636:Aminosalicylic Acids / Q000378:metabolism*; D002457:Cell Extracts / Q000494:pharmacology; D003998:Dicarboxylic Acids / Q000378:metabolism; D049308:Dioxygenases; D006863:Hydrogen-Ion Concentration; D019804:Mesalamine; D009016:Moraxella / Q000378:metabolism*; D010100:Oxygen / Q000493:pharmacokinetics; D010105:Oxygenases / Q000302:isolation & purification; D011549:Pseudomonas / Q000378:metabolism*
D000636:Aminosalicylic Acids; D002457:Cell Extracts; D003998:Dicarboxylic Acids; C073688:fumarylpyruvate; D019804:Mesalamine; D010105:Oxygenases; C073689:5-aminosalicylic acid 1,2-dioxygenase; D049308:Dioxygenases; C026247:gentisate 1,2-dioxygenase; D010100:Oxygen