Details zur Publikation

Kategorie Textpublikation
Referenztyp Zeitschriften
DOI 10.1002/cbic.202200632
Volltext Shareable Link
Titel (primär) Bacterial dehydrogenases facilitate oxidative inactivation and bioremediation of chloramphenicol
Autor Zhang, L.; Toplak, M.; Saleem-Batcha, R.; Höing, L.; Jakob, R.; Jehmlich, N. ORCID logo ; von Bergen, M.; Maier, T.; Teufel, R.
Journal / Serie Chembiochem
Erscheinungsjahr 2023
Department MOLSYB
Band/Volume 24
Heft 2
Seite von e202200632
Sprache englisch
Topic T9 Healthy Planet
Keywords antimicrobial resistance; bioremediation; antibiotics; flavoenzymes; chloramphenicol
Abstract Antimicrobial resistance represents a major threat to human health and knowledge of the underlying mechanisms is therefore vital. Here, we report the discovery and characterization of oxidoreductases that inactivate the broad-spectrum antibiotic chloramphenicol via dual oxidation of the C3-hydroxyl group. Accordingly, chloramphenicol oxidation either depends on standalone glucose-methanol-choline (GMC)-type flavoenzymes, or on additional aldehyde dehydrogenases that boost overall turnover. These enzymes also enable the inactivation of the chloramphenicol analogs thiamphenicol and azidamfenicol, but not of the C3-fluorinated florfenicol. Notably, distinct isofunctional enzymes can be found in Gram-positive (e.g., Streptomyces sp.) and Gram-negative (e.g., Sphingobium sp.) bacteria, which presumably evolved their selectivity for chloramphenicol independently based on phylogenetic analyses. Mechanistic and structural studies provide further insights into the catalytic mechanisms of these biotechnologically interesting enzymes, which, in sum, are both a curse and a blessing by contributing to the spread of antibiotic resistance as well as to the bioremediation of chloramphenicol.
dauerhafte UFZ-Verlinkung
Zhang, L., Toplak, M., Saleem-Batcha, R., Höing, L., Jakob, R., Jehmlich, N., von Bergen, M., Maier, T., Teufel, R. (2023):
Bacterial dehydrogenases facilitate oxidative inactivation and bioremediation of chloramphenicol
ChemBioChem 24 (2), e202200632