Dereplication of Natural Product Antifungals via Liquid Chromatography–Tandem Mass Spectrometry and Chemical Genomics
Recently expanded reports of multidrug-resistant fungal infections underscore the need to develop new and more efficient methods for antifungal drug discovery. A ubiquitous problem in natural product drug discovery campaigns is the rediscovery of known compounds or their relatives; accordingly, we h...
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MDPI AG
2024-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/30/1/77 |
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| author | Nathaniel J. Brittin David J. Aceti Doug R. Braun Josephine M. Anderson Spencer S. Ericksen Scott R. Rajski Cameron R. Currie David R. Andes Tim S. Bugni |
| author_facet | Nathaniel J. Brittin David J. Aceti Doug R. Braun Josephine M. Anderson Spencer S. Ericksen Scott R. Rajski Cameron R. Currie David R. Andes Tim S. Bugni |
| author_sort | Nathaniel J. Brittin |
| collection | DOAJ |
| description | Recently expanded reports of multidrug-resistant fungal infections underscore the need to develop new and more efficient methods for antifungal drug discovery. A ubiquitous problem in natural product drug discovery campaigns is the rediscovery of known compounds or their relatives; accordingly, we have integrated Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS) for structural dereplication and Yeast Chemical Genomics for bioprocess evaluation into a screening platform to identify such compounds early in the screening process. We identified 450 fractions inhibiting <i>Candida albicans</i> and the resistant strains of <i>C. auris</i> and <i>C. glabrata</i> among more than 40,000 natural product fractions. LC-MS/MS and chemical genomics were then used to identify those with known chemistry and mechanisms of action. The parallel deployment of these orthogonal methods improved the detection of unwanted compound classes over the methods applied individually. |
| format | Article |
| id | doaj-art-08ce9d878d7243bf8a196a69fc7c0f88 |
| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-08ce9d878d7243bf8a196a69fc7c0f882025-01-10T13:18:48ZengMDPI AGMolecules1420-30492024-12-013017710.3390/molecules30010077Dereplication of Natural Product Antifungals via Liquid Chromatography–Tandem Mass Spectrometry and Chemical GenomicsNathaniel J. Brittin0David J. Aceti1Doug R. Braun2Josephine M. Anderson3Spencer S. Ericksen4Scott R. Rajski5Cameron R. Currie6David R. Andes7Tim S. Bugni8Pharmaceutical Sciences Division, University of Wisconsin-Madison, Madison, WI 53705, USASmall Molecule Screening Facility, UW Carbone Cancer Center, Madison, WI 53792, USAPharmaceutical Sciences Division, University of Wisconsin-Madison, Madison, WI 53705, USAPharmaceutical Sciences Division, University of Wisconsin-Madison, Madison, WI 53705, USASmall Molecule Screening Facility, UW Carbone Cancer Center, Madison, WI 53792, USAPharmaceutical Sciences Division, University of Wisconsin-Madison, Madison, WI 53705, USADepartment of Biochemistry and Biomedical Sciences, M.G. DeGroote Institute for Infectious Disease Research, David Braley Centre for Antibiotic Discovery, McMaster University, Hamilton, ON L8S 4L8, CanadaDepartment of Medical Microbiology and Immunology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706, USAPharmaceutical Sciences Division, University of Wisconsin-Madison, Madison, WI 53705, USARecently expanded reports of multidrug-resistant fungal infections underscore the need to develop new and more efficient methods for antifungal drug discovery. A ubiquitous problem in natural product drug discovery campaigns is the rediscovery of known compounds or their relatives; accordingly, we have integrated Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS) for structural dereplication and Yeast Chemical Genomics for bioprocess evaluation into a screening platform to identify such compounds early in the screening process. We identified 450 fractions inhibiting <i>Candida albicans</i> and the resistant strains of <i>C. auris</i> and <i>C. glabrata</i> among more than 40,000 natural product fractions. LC-MS/MS and chemical genomics were then used to identify those with known chemistry and mechanisms of action. The parallel deployment of these orthogonal methods improved the detection of unwanted compound classes over the methods applied individually.https://www.mdpi.com/1420-3049/30/1/77antifungalnatural productsmechanism of actiondereplicationchemical genomicsmetabolomics |
| spellingShingle | Nathaniel J. Brittin David J. Aceti Doug R. Braun Josephine M. Anderson Spencer S. Ericksen Scott R. Rajski Cameron R. Currie David R. Andes Tim S. Bugni Dereplication of Natural Product Antifungals via Liquid Chromatography–Tandem Mass Spectrometry and Chemical Genomics Molecules antifungal natural products mechanism of action dereplication chemical genomics metabolomics |
| title | Dereplication of Natural Product Antifungals via Liquid Chromatography–Tandem Mass Spectrometry and Chemical Genomics |
| title_full | Dereplication of Natural Product Antifungals via Liquid Chromatography–Tandem Mass Spectrometry and Chemical Genomics |
| title_fullStr | Dereplication of Natural Product Antifungals via Liquid Chromatography–Tandem Mass Spectrometry and Chemical Genomics |
| title_full_unstemmed | Dereplication of Natural Product Antifungals via Liquid Chromatography–Tandem Mass Spectrometry and Chemical Genomics |
| title_short | Dereplication of Natural Product Antifungals via Liquid Chromatography–Tandem Mass Spectrometry and Chemical Genomics |
| title_sort | dereplication of natural product antifungals via liquid chromatography tandem mass spectrometry and chemical genomics |
| topic | antifungal natural products mechanism of action dereplication chemical genomics metabolomics |
| url | https://www.mdpi.com/1420-3049/30/1/77 |
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