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Outlines of an “exploding” network of metabolites generated from the fluoroquinolone enrofloxacin by the brown rot fungus Gloeophyllum striatum

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Abstract

Degradation of the veterinary fluoroquinolone antibiotic enrofloxacin (EFL) was studied with three strains of Gloeophyllum, basidiomycetous fungi thought to produce extracellular hydroxyl radicals. Metabolites generated in a mineral medium were analyzed by combined high-performance liquid chromatography/high-resolution electrospray ionization mass spectrometry. Their origin was inferred from peak doublets representing 12C and 14C isotopomers detected at a defined proportion. From each exact molecular mass, the molecular formula was derived for which the most probable chemical structure was postulated, using for guidance 18 known EFL metabolites. All supernatants provided similar metabolite patterns, with the most comprehensive consisting of 87 compounds. These metabolites belonged to five families headed by EFL, its oxidatively decarboxylated or defluorinated congeners, an isatin-, and an anthranilic acid-type derivative. Metabolites hydroxylated in the aromatic part suggested the formation of three catechols and two oxidizable ortho-aminophenol-type compounds. After oxidation to the respective ortho-quinones or ortho-quinone imines and oxidative ring cleavage at one of three alternative sites, the formation of various cis,cis-muconic acid-type derivatives is likely, one of which could be detected. Anthranilic acid-type compounds provided two additional sites for ortho-aminophenol formation and aromatic ring cleavage. An “exploding” network of diverse EFL congeners produced by Gloeophyllum suggests the broad utility of our model for studying biodegradation.

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Acknowledgements

The technical assistance of A. Lagojda, Bayer CropScience AG, in recording the HRMS spectra is gratefully acknowledged. We thank P. Wood, Bristol, UK, and J. Wesener, Bayer Industry Services, Leverkusen, for advice.

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Correspondence to H.-G. Wetzstein.

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Karl, W., Schneider, J. & Wetzstein, H. Outlines of an “exploding” network of metabolites generated from the fluoroquinolone enrofloxacin by the brown rot fungus Gloeophyllum striatum . Appl Microbiol Biotechnol 71, 101–113 (2006). https://doi.org/10.1007/s00253-005-0177-5

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Keywords

  • Piperazine
  • Enrofloxacin
  • Oxidative Cleavage
  • Oxidative Decarboxylation
  • Piperazine Ring