{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T20:54:07Z","timestamp":1774644847979,"version":"3.50.1"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T00:00:00Z","timestamp":1692835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Chem."],"abstract":"<jats:p><jats:italic>Cupriavidus necator<\/jats:italic> H16 is known to be a rich source of linear lipopeptide siderophores when grown under iron-depleted conditions; prior literature termed these compounds cupriachelins. These small molecules bear <jats:italic>\u03b2<\/jats:italic>-hydroxyaspartate moieties that contribute to a photoreduction of iron when bound as ferric cupriachelin. Here, we present structural assignment of cupriachelins from <jats:italic>C. necator<\/jats:italic> B-4383 grown under iron limitation. The characterization of B-4383 cupriachelins is based on MS\/MS fragmentation analysis, which was confirmed by 1D- and 2D-NMR for the most abundant analog (<jats:bold>1<\/jats:bold>). The cupriachelin congeners distinguish these two strains with differences in the preferred lipid tail; however, our rigorous metabolomic investigation also revealed minor analogs with changes in the peptide core, hinting at a potential mechanism by which these siderophores may reduce biologically unavailable ferric iron (<jats:bold>4\u20136<\/jats:bold>). Antifungal screening of the <jats:italic>C. necator<\/jats:italic> B-4383 supernatant extract and the isolated cupriachelin analog (<jats:bold>1<\/jats:bold>) revealed inhibitory activity against <jats:italic>Cryptococcus neoformans<\/jats:italic>, with IC<jats:sub>50<\/jats:sub> values of 16.6 and 3.2\u00a0\u03bcg\/mL, respectively. This antifungal activity could be explained by the critical role of the iron acquisition pathway in the growth and pathogenesis of the <jats:italic>C. neoformans<\/jats:italic> fungal pathogen.<\/jats:p>","DOI":"10.3389\/fchem.2023.1256962","type":"journal-article","created":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T21:54:36Z","timestamp":1692914076000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Comparative metabolomic profiling of Cupriavidus necator B-4383 revealed production of cupriachelin siderophores, one with activity against Cryptococcus neoformans"],"prefix":"10.3389","volume":"11","author":[{"given":"Mohammed M. 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