uni-leipzig-open-access/json/cbic.202200632

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Here, we report the discovery and characterization of oxidoreductases that inactivate the broad\u2010spectrum antibiotic chloramphenicol via dual oxidation of the C3\u2010hydroxyl group. Accordingly, chloramphenicol oxidation either depends on standalone glucose\u2010methanol\u2010choline (GMC)\u2010type 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\u2010fluorinated florfenicol. Notably, distinct isofunctional enzymes can be found in Gram\u2010positive (e.\u2009g., <jats:italic>Streptomyces<\/jats:italic> sp.) and Gram\u2010negative (e.\u2009g., <jats:italic>Sphingobium<\/jats:italic> 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.<\/jats:p>","DOI":"10.1002\/cbic.202200632","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T09:46:06Z","timestamp":1668073566000},"update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Bacterial Dehydrogenases Facilitate Oxidative Inactivation and Bioremediation of Chloramphenicol"],"prefix":"10.1002","volume":"24","author":[{"given":"Lei","family":"Zhang","sequence":"first","affiliation":[{"name":"Faculty of Biology University of Freiburg Sch\u00e4nzlestrasse 1 79104 Freiburg Germany"}]},{"given":"Marina","family":"Toplak","sequence":"additional","affiliation":[{"name":"Faculty of Biology University of Freiburg Sch\u00e4nzlestrasse 1 79104 Freiburg Germany"}]},{"given":"Raspudin","family":"Saleem\u2010Batcha","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences University of Freiburg Albertstrasse 25 79104 Freiburg Germany"}]},{"given":"Lars","family":"H\u00f6ing","sequence":"additional","affiliation":[{"name":"Pharmaceutical Biology Department of Pharmaceutical Sciences University of Basel Klingelbergstrasse 50 4056 Basel Switzerland"}]},{"ORCID":"http:\/\/orcid.org\/0000-0002-6451-8656","authenticated-orcid":false,"given":"Roman","family":"Jakob","sequence":"additional","affiliation":[{"name":"Biozentrum University of Basel Spitalstrasse 41 4056 Basel Switzerland"}]},{"ORCID":"http:\/\/orcid.org\/0000-0002-5638-6868","authenticated-orcid":false,"given":"Nico","family":"Jehmlich","sequence":"additional","affiliation":[{"name":"Department of Molecular Systems Biology Helmholtz-Centre for Environmental Research UFZ GmbH Leipzig Germany"},{"name":"German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig Puschstra\u00dfe 4 04103 Leipzig Germany"},{"name":"University of Leipzig Faculty of Life Sciences Institute of Biochemistry Br\u00fcderstra\u00dfe 34 04103 Leipzig Germany"}]},{"given":"Martin","family":"von Bergen","sequence":"additional","affiliation":[{"name":"Department of Molecular Systems Biology Helmholtz-Centre for Environmental Research UFZ GmbH Leipzig Germany"},{"name":"German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig Puschstra\u00dfe 4 04103 Leipzig Germany"},{"name":"University of Leipzig Faculty of Life Sciences Institute of Biochemistry Br\u00fcderstra\u00dfe 34 04103 Leipzig Germany"}]},{"ORCID":"http:\/\/orcid.org\/0000-0002-7459-1363","authenticated-orcid":false,"given":"Timm","family":"Maier","sequence":"additional","affiliation":[{"name":"Biozentrum University of Basel Spitalstrasse 41 4056 Basel Switzerland"}]},{"ORCID":"http:\/\/orcid.org\/0000-0001-5863-7248","authenticated-orcid":false,"given":"Robin","family":"Teufel","sequence":"additional","affiliation":[{"name":"Pharmaceutical Biology Department of Pharmaceutical Sciences University of Basel Klingelbergstrasse 50 4056 Basel Switzerland"}]}],"member":"311","published-online":{"date-parts":[[2022,12,5]]},"reference":[{"key":"e_1_2_8_1_1","unstructured":"C. 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