title: Fungal Biotransformation of Tetracycline Antibiotics.
abstract: The commercial antibiotics tetracycline (3), minocycline (4), chlortetracycline (5), oxytetracycline (6), and doxycycline (7) were biotransformed by a marine-derived fungus Paecilomyces sp. to yield seco-cyclines A-H (9-14, 18 and 19) and hemi-cyclines A-E (20-24). Structures were assigned by detailed spectroscopic analysis, and in the case of 10 X-ray crystallography. Parallel mechanisms account for substrate-product specificity, where 3-5 yield seco-cyclines and 6 and 7 yield hemi-cyclines. The susceptibility of 3-7 to fungal biotransformation is indicative of an unexpected potential for tetracycline "degradation" (i.e., antibiotic resistance) in fungal genomes. Significantly, the fungal-derived tetracycline-like viridicatumtoxins are resistant to fungal biotransformation, providing chemical insights that could inform the development of new tetracycline antibiotics resistant to enzymatic degradation.
authors.affiliation: Institute for Molecular Bioscience and ‡School of Chemistry and Molecular Biosciences, The University of Queensland , St. Lucia, QLD 4072, Australia.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Shang
authors.affiliation: Institute for Molecular Bioscience and ‡School of Chemistry and Molecular Biosciences, The University of Queensland , St. Lucia, QLD 4072, Australia.
authors.forename: Angela A
authors.initials: AA
authors.lastname: Salim
authors.affiliation: Institute for Molecular Bioscience and ‡School of Chemistry and Molecular Biosciences, The University of Queensland , St. Lucia, QLD 4072, Australia.
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Khalil
authors.affiliation: Institute for Molecular Bioscience and ‡School of Chemistry and Molecular Biosciences, The University of Queensland , St. Lucia, QLD 4072, Australia.
authors.forename: Paul V
authors.initials: PV
authors.lastname: Bernhardt
authors.affiliation: Institute for Molecular Bioscience and ‡School of Chemistry and Molecular Biosciences, The University of Queensland , St. Lucia, QLD 4072, Australia.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Capon
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001711:Biotransformation; D002751:Chlortetracycline / Q000737:chemistry; D018360:Crystallography, X-Ray; D004318:Doxycycline / Q000737:chemistry; D025141:Drug Resistance, Fungal; D005285:Fermentation; D005658:Fungi / Q000378:metabolism; D016681:Genome, Fungal; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000737:chemistry; D008974:Mollusca / Q000382:microbiology; D010100:Oxygen / Q000737:chemistry; D010118:Oxytetracycline / Q000737:chemistry; D013752:Tetracycline / Q000737:chemistry*; D014640:Vancomycin / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D013752:Tetracycline; D008911:Minocycline; D004318:Doxycycline; D010100:Oxygen; D002751:Chlortetracycline; D010118:Oxytetracycline