Miniaturized high-throughput conversion of fungal strain collections into chemically characterized extract libraries for antimicrobial discovery
Natural products remain vital to drug discovery, with fungi representing an underexplored source of bioactive compounds. Despite advances in LC-MS-based metabolomics that facilitate dereplication and chemical profiling of natural extracts, the rate of new discoveries has not significantly increased....
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-07-01
|
| Series: | Frontiers in Chemistry |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2025.1630332/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849428422779994112 |
|---|---|
| author | Alexandre Bory Alexandre Bory Alexandre Luscher Nicole Lecoultre Thilo Köhler Sylvain Schnee Katia Gindro Jean-Luc Wolfender Jean-Luc Wolfender |
| author_facet | Alexandre Bory Alexandre Bory Alexandre Luscher Nicole Lecoultre Thilo Köhler Sylvain Schnee Katia Gindro Jean-Luc Wolfender Jean-Luc Wolfender |
| author_sort | Alexandre Bory |
| collection | DOAJ |
| description | Natural products remain vital to drug discovery, with fungi representing an underexplored source of bioactive compounds. Despite advances in LC-MS-based metabolomics that facilitate dereplication and chemical profiling of natural extracts, the rate of new discoveries has not significantly increased. This stagnation may be attributed to the laborious process of culturing and extracting large microbial collections. At the same time, rising antimicrobial resistance, particularly among ESKAPE pathogens, highlights the urgent need for new scaffolds. To address these challenges, we developed FLECS-96 (Fungal Library Extract Conversion and Screening in 96-well plate format), a high-throughput platform that efficiently transforms fungal strains into chemically characterized extract libraries. FLECS-96 combines miniaturized fungal liquid culture with streamlined sample preparation, systematic metabolomic profiling, and biological evaluation of the extracts. Here, we describe the development and validation of this workflow, and demonstrate its utility through the rapid identification of compounds active against S. aureus. FLECS-96 provides a scalable solution to accelerate antimicrobial lead discovery from fungal sources. |
| format | Article |
| id | doaj-art-2bbe42ed505c4ea28d2ae31d0907c77a |
| institution | Kabale University |
| issn | 2296-2646 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj-art-2bbe42ed505c4ea28d2ae31d0907c77a2025-08-20T03:28:43ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462025-07-011310.3389/fchem.2025.16303321630332Miniaturized high-throughput conversion of fungal strain collections into chemically characterized extract libraries for antimicrobial discoveryAlexandre Bory0Alexandre Bory1Alexandre Luscher2Nicole Lecoultre3Thilo Köhler4Sylvain Schnee5Katia Gindro6Jean-Luc Wolfender7Jean-Luc Wolfender8School of Pharmaceutical Sciences, University of Geneva, Centre Medical Universitaire, Geneva, SwitzerlandInstitute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Centre Medical Universitaire, Geneva, SwitzerlandDepartment of Microbiology and Molecular Medicine, University of Geneva, Geneva, SwitzerlandMycology Group, Research Department Plant Protection, Agroscope, Nyon, SwitzerlandDepartment of Microbiology and Molecular Medicine, University of Geneva, Geneva, SwitzerlandMycology Group, Research Department Plant Protection, Agroscope, Nyon, SwitzerlandMycology Group, Research Department Plant Protection, Agroscope, Nyon, SwitzerlandSchool of Pharmaceutical Sciences, University of Geneva, Centre Medical Universitaire, Geneva, SwitzerlandInstitute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Centre Medical Universitaire, Geneva, SwitzerlandNatural products remain vital to drug discovery, with fungi representing an underexplored source of bioactive compounds. Despite advances in LC-MS-based metabolomics that facilitate dereplication and chemical profiling of natural extracts, the rate of new discoveries has not significantly increased. This stagnation may be attributed to the laborious process of culturing and extracting large microbial collections. At the same time, rising antimicrobial resistance, particularly among ESKAPE pathogens, highlights the urgent need for new scaffolds. To address these challenges, we developed FLECS-96 (Fungal Library Extract Conversion and Screening in 96-well plate format), a high-throughput platform that efficiently transforms fungal strains into chemically characterized extract libraries. FLECS-96 combines miniaturized fungal liquid culture with streamlined sample preparation, systematic metabolomic profiling, and biological evaluation of the extracts. Here, we describe the development and validation of this workflow, and demonstrate its utility through the rapid identification of compounds active against S. aureus. FLECS-96 provides a scalable solution to accelerate antimicrobial lead discovery from fungal sources.https://www.frontiersin.org/articles/10.3389/fchem.2025.1630332/fulldrug discoveryfungal strainsmetabolomicsantimicrobialESKAPEAMR |
| spellingShingle | Alexandre Bory Alexandre Bory Alexandre Luscher Nicole Lecoultre Thilo Köhler Sylvain Schnee Katia Gindro Jean-Luc Wolfender Jean-Luc Wolfender Miniaturized high-throughput conversion of fungal strain collections into chemically characterized extract libraries for antimicrobial discovery Frontiers in Chemistry drug discovery fungal strains metabolomics antimicrobial ESKAPE AMR |
| title | Miniaturized high-throughput conversion of fungal strain collections into chemically characterized extract libraries for antimicrobial discovery |
| title_full | Miniaturized high-throughput conversion of fungal strain collections into chemically characterized extract libraries for antimicrobial discovery |
| title_fullStr | Miniaturized high-throughput conversion of fungal strain collections into chemically characterized extract libraries for antimicrobial discovery |
| title_full_unstemmed | Miniaturized high-throughput conversion of fungal strain collections into chemically characterized extract libraries for antimicrobial discovery |
| title_short | Miniaturized high-throughput conversion of fungal strain collections into chemically characterized extract libraries for antimicrobial discovery |
| title_sort | miniaturized high throughput conversion of fungal strain collections into chemically characterized extract libraries for antimicrobial discovery |
| topic | drug discovery fungal strains metabolomics antimicrobial ESKAPE AMR |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2025.1630332/full |
| work_keys_str_mv | AT alexandrebory miniaturizedhighthroughputconversionoffungalstraincollectionsintochemicallycharacterizedextractlibrariesforantimicrobialdiscovery AT alexandrebory miniaturizedhighthroughputconversionoffungalstraincollectionsintochemicallycharacterizedextractlibrariesforantimicrobialdiscovery AT alexandreluscher miniaturizedhighthroughputconversionoffungalstraincollectionsintochemicallycharacterizedextractlibrariesforantimicrobialdiscovery AT nicolelecoultre miniaturizedhighthroughputconversionoffungalstraincollectionsintochemicallycharacterizedextractlibrariesforantimicrobialdiscovery AT thilokohler miniaturizedhighthroughputconversionoffungalstraincollectionsintochemicallycharacterizedextractlibrariesforantimicrobialdiscovery AT sylvainschnee miniaturizedhighthroughputconversionoffungalstraincollectionsintochemicallycharacterizedextractlibrariesforantimicrobialdiscovery AT katiagindro miniaturizedhighthroughputconversionoffungalstraincollectionsintochemicallycharacterizedextractlibrariesforantimicrobialdiscovery AT jeanlucwolfender miniaturizedhighthroughputconversionoffungalstraincollectionsintochemicallycharacterizedextractlibrariesforantimicrobialdiscovery AT jeanlucwolfender miniaturizedhighthroughputconversionoffungalstraincollectionsintochemicallycharacterizedextractlibrariesforantimicrobialdiscovery |