Fungal Biotransformation of Tetracycline Antibiotics

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.