| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 70171 | Journal of Molecular Catalysis B: Enzymatic | 2011 | 6 Pages |
Several Streptomyces and Bacillus strains were examined for their ability to transform the anti-inflammatory drug flurbiprofen 1 to the hydroxylated metabolites that are found in humans after ingestion of this compound. Of the seven Streptomyces spp. examined, all but one transformed flurbiprofen to the main mammalian metabolite 4′-hydroxyflurbiprofen 2, and the majority also produced 3′,4′-dihydroxyflurbiprofen 3. Three strains, Streptomyces griseus DSM40236 and ATCC13273, and Streptomyces subrutilis DSM40445, also elaborated 3′-methoxy, 4′-hydroxy-flurbiprofen 4. None of the Bacillus spp. examined yielded these metabolites. Examination of the extracted supernatants of Streptomyces lavenduligriseus and Streptomyces rimosus by fluorine-19 nuclear magnetic resonance (19F NMR), indicated new resonances and these new fluorometabolites were purified by HPLC and revealed to be flurbiprofenamide 5 and 7-hydroxyflurbiprofenamide 6 after MS and NMR analyses. Subsequent re-examination of the culture supernatants from Bacillus subtilis IM7, Bacillus megaterium NCIMB8291 and B. megaterium ATTC14581 showed that these strains also produced 5 and 6. Resting cell investigations suggested that the amidation reaction employed nitrogen from an as yet unidentified amino acid.
Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Biotransformation of flurbiprofen in Streptomyces and Bacillus spp. investigated. ► Mammalian hydroxylated metabolites detected in most Streptomyces spp. ► Additional fluorometabolites determined by fluorine-19 NMR spectroscopy. ► Identified as amidated metabolites after isolation. ► Also detected as biotransformation products in Bacillus cultures.
