8B7S

Crystal structure of the Chloramphenicol-inactivating oxidoreductase from Novosphingobium sp

Summary for 8B7S

• Entry DOI: 10.2210/pdb8b7s/pdb
• Descriptor: Chloramphenicol-inactivating oxidoreductase, FLAVIN-ADENINE DINUCLEOTIDE (3 entities in total)
• Functional Keywords: cap-ohase, chloramphenicol, oxidoreductase, flavin, fad, cap, anitmicrobial resistance, flavoprotein
• Biological source: Novosphingobium sp. B 225
• Total number of polymer chains: 1
• Total formula weight: 59505.05

Authors

Zhang, L.,Toplak, M.,Saleem-Batcha, R.,Hoeing, L.,Jakob, R.P.,Jehmlich, N.,von Bergen, M.,Maier, T.,Teufel, R. (deposition date: 2022-10-03, release date: 2022-11-16, Last modification date: 2024-05-01)

Primary citation

Zhang, L.,Toplak, M.,Saleem-Batcha, R.,Hoing, L.,Jakob, R.,Jehmlich, N.,von Bergen, M.,Maier, T.,Teufel, R.
Bacterial Dehydrogenases Facilitate Oxidative Inactivation and Bioremediation of Chloramphenicol.
Chembiochem, 24:e202200632-e202200632, 2023

PubMed 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 analogues 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.

PubMed: 36353978
DOI: 10.1002/cbic.202200632

Experimental method

X-RAY DIFFRACTION (2.1 Å)