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One such promising structure is the acetyl\u2010CoA carboxylase (ACC) inhibitor moiramide B which shows strong antibacterial activity against gram\u2010positive bacteria such as <jats:italic>Bacillus subtilis<\/jats:italic> and weaker activities against gram\u2010negative bacteria. However, the narrow structure\u2010activity relationship of the pseudopeptide unit of moiramide B represents a formidable challenge for any optimization strategy. In contrast, the lipophilic fatty acid tail is considered an unspecific vehicle responsible only for the transport of moiramide into the bacterial cell. Here we show that the sorbic acid unit, in fact, is highly relevant for ACC inhibition. A hitherto undescribed sub\u2010pocket at the end of the sorbic acid channel binds strongly aromatic rings and allows the development of moiramide derivatives with altered antibacterial profiles including anti\u2010tubercular activity.<\/jats:p>","DOI":"10.1002\/cmdc.202200631","type":"journal-article","created":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T10:20:14Z","timestamp":1678270814000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Reinvestigation of the Role of the Sorbic Acid Tail on the Antibacterial and Anti\u2010Tuberculosis Properties of Moiramide B"],"prefix":"10.1002","volume":"18","author":[{"given":"Irina","family":"Kollmorgen","sequence":"first","affiliation":[{"name":"School of Mathematics and Natural Sciences Department of Chemistry and Biology University of Wuppertal  Gaussstrasse 20 42119 Wuppertal Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie","family":"Bachmann","sequence":"additional","affiliation":[{"name":"Faculty of Biology and Biotechnology Ruhr University Bochum  Universit\u00e4tsstrasse 150 44780 Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Dal Molin","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Cologne  Cologne Germany"},{"name":"Lead Discovery Center GmbH  Otto-Hahn-Strasse 15 44227 Dortmund Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten","family":"Degenhart","sequence":"additional","affiliation":[{"name":"Lead Discovery Center GmbH  Otto-Hahn-Strasse 15 44227 Dortmund Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eldar","family":"Zent","sequence":"additional","affiliation":[{"name":"Lead Discovery Center GmbH  Otto-Hahn-Strasse 15 44227 Dortmund Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vikram","family":"Pareek","sequence":"additional","affiliation":[{"name":"Faculty of Biology and Biotechnology Ruhr University Bochum  Universit\u00e4tsstrasse 150 44780 Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uwe","family":"Koch","sequence":"additional","affiliation":[{"name":"Lead Discovery Center GmbH  Otto-Hahn-Strasse 15 44227 Dortmund Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Rybniker","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Cologne  Cologne Germany"},{"name":"Lead Discovery Center GmbH  Otto-Hahn-Strasse 15 44227 Dortmund Germany"},{"name":"German Center for Infection Research (DZIF)  Partner Site Bonn-Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nils","family":"Metzler\u2010Nolte","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Biochemistry Inorganic Chemistry I \u2013 Bioinorganic Chemistry Ruhr University Bochum  Universit\u00e4tsstrasse 150 44780 Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raphael","family":"Stoll","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Biochemistry Biomolecular Spectroscopy and RUBiospec|NMR Ruhr University Bochum  Universit\u00e4tsstrasse 150 44780 Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bert","family":"Klebl","sequence":"additional","affiliation":[{"name":"Lead Discovery Center GmbH  Otto-Hahn-Strasse 15 44227 Dortmund Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia Elisabeth","family":"Bandow","sequence":"additional","affiliation":[{"name":"Faculty of Biology and Biotechnology Ruhr University Bochum  Universit\u00e4tsstrasse 150 44780 Bochum Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1321-0595","authenticated-orcid":false,"given":"J\u00fcrgen","family":"Scherkenbeck","sequence":"additional","affiliation":[{"name":"School of Mathematics and Natural Sciences Department of Chemistry and Biology University of Wuppertal  Gaussstrasse 20 42119 Wuppertal Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,4,18]]},"reference":[{"key":"e_1_2_10_1_1","unstructured":"E. 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