TY - JOUR
T1 - Fungal Biotransformation of Tetracycline Antibiotics
AU - Shang, Zhuo
AU - Salim, Angela A.
AU - Khalil, Zeinab
AU - Bernhardt, Paul V.
AU - Capon, Robert J.
PY - 2016/8/5
Y1 - 2016/8/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84981203570&partnerID=8YFLogxK
U2 - 10.1021/acs.joc.6b01272
DO - 10.1021/acs.joc.6b01272
M3 - Article
C2 - 27419475
AN - SCOPUS:84981203570
SN - 0022-3263
VL - 81
SP - 6186
EP - 6194
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 15
ER -
