Comparative metabolomic profiling of Cupriavidus necator B-4383 revealed production of cupriachelin siderophores, one with activity against Cryptococcus neoformans
Cupriavidus necator 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 β-hydroxyaspartate moieties that contribute to a photoreduction of iron when bound as f...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2023.1256962/full |
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| author | Mohammed M. A. Ahmed Mohammed M. A. Ahmed Siddarth K. Tripathi Paul D. Boudreau |
| author_facet | Mohammed M. A. Ahmed Mohammed M. A. Ahmed Siddarth K. Tripathi Paul D. Boudreau |
| author_sort | Mohammed M. A. Ahmed |
| collection | DOAJ |
| description | Cupriavidus necator 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 β-hydroxyaspartate moieties that contribute to a photoreduction of iron when bound as ferric cupriachelin. Here, we present structural assignment of cupriachelins from C. necator 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 (1). 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 (4–6). Antifungal screening of the C. necator B-4383 supernatant extract and the isolated cupriachelin analog (1) revealed inhibitory activity against Cryptococcus neoformans, with IC50 values of 16.6 and 3.2 μg/mL, respectively. This antifungal activity could be explained by the critical role of the iron acquisition pathway in the growth and pathogenesis of the C. neoformans fungal pathogen. |
| first_indexed | 2024-03-12T13:29:58Z |
| format | Article |
| id | doaj.art-ed99f9ed3e074e009dfea2a7a7117a5f |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-03-12T13:29:58Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-ed99f9ed3e074e009dfea2a7a7117a5f2023-08-24T21:54:33ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462023-08-011110.3389/fchem.2023.12569621256962Comparative metabolomic profiling of Cupriavidus necator B-4383 revealed production of cupriachelin siderophores, one with activity against Cryptococcus neoformansMohammed M. A. Ahmed0Mohammed M. A. Ahmed1Siddarth K. Tripathi2Paul D. Boudreau3Boudreau Lab, Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, Oxford, MS, United StatesDepartment of Pharmacognosy, Al-Azhar University, Cairo, EgyptNational Center for Natural Products Research, School of Pharmacy, University of Mississippi, Oxford, MS, United StatesBoudreau Lab, Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, Oxford, MS, United StatesCupriavidus necator 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 β-hydroxyaspartate moieties that contribute to a photoreduction of iron when bound as ferric cupriachelin. Here, we present structural assignment of cupriachelins from C. necator 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 (1). 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 (4–6). Antifungal screening of the C. necator B-4383 supernatant extract and the isolated cupriachelin analog (1) revealed inhibitory activity against Cryptococcus neoformans, with IC50 values of 16.6 and 3.2 μg/mL, respectively. This antifungal activity could be explained by the critical role of the iron acquisition pathway in the growth and pathogenesis of the C. neoformans fungal pathogen.https://www.frontiersin.org/articles/10.3389/fchem.2023.1256962/fullcupriachelinsiderophoremetabolomics (LC-MS)Cupriavidus necatormass spectrometry |
| spellingShingle | Mohammed M. A. Ahmed Mohammed M. A. Ahmed Siddarth K. Tripathi Paul D. Boudreau Comparative metabolomic profiling of Cupriavidus necator B-4383 revealed production of cupriachelin siderophores, one with activity against Cryptococcus neoformans Frontiers in Chemistry cupriachelin siderophore metabolomics (LC-MS) Cupriavidus necator mass spectrometry |
| title | Comparative metabolomic profiling of Cupriavidus necator B-4383 revealed production of cupriachelin siderophores, one with activity against Cryptococcus neoformans |
| title_full | Comparative metabolomic profiling of Cupriavidus necator B-4383 revealed production of cupriachelin siderophores, one with activity against Cryptococcus neoformans |
| title_fullStr | Comparative metabolomic profiling of Cupriavidus necator B-4383 revealed production of cupriachelin siderophores, one with activity against Cryptococcus neoformans |
| title_full_unstemmed | Comparative metabolomic profiling of Cupriavidus necator B-4383 revealed production of cupriachelin siderophores, one with activity against Cryptococcus neoformans |
| title_short | Comparative metabolomic profiling of Cupriavidus necator B-4383 revealed production of cupriachelin siderophores, one with activity against Cryptococcus neoformans |
| title_sort | comparative metabolomic profiling of cupriavidus necator b 4383 revealed production of cupriachelin siderophores one with activity against cryptococcus neoformans |
| topic | cupriachelin siderophore metabolomics (LC-MS) Cupriavidus necator mass spectrometry |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2023.1256962/full |
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