ORIGINAL RESEARCH article

Front. Chem.

Sec. Medicinal and Pharmaceutical Chemistry

Volume 13 - 2025 | doi: 10.3389/fchem.2025.1630332

This article is part of the Research TopicBioactive Natural Products for Health: Isolation, Structural Elucidation, Biological Evaluation, Structure-activity Relationship, and Mechanism - Volume IIView all 6 articles

Miniaturized High-Throughput Conversion of Fungal Strain Collections into Chemically Characterized Extract Libraries for Antimicrobial Discovery

Provisionally accepted
Alexandre Jean BoryAlexandre Jean Bory1,2*Alexandre LuscherAlexandre Luscher3Nicole LecoultreNicole Lecoultre4Thilo KöhlerThilo Köhler3Sylvain SchneeSylvain Schnee4Katia GindroKatia Gindro4Wolfender Jean-LucWolfender Jean-Luc1,2*
  • 1Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU, Geneva, Switzerland
  • 2School of Pharmaceutical Sciences, University of Geneva, CMU, Geneva, Switzerland
  • 3Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland
  • 4Mycology Group, Research Department Plant Protection, Agroscope, Nyons, Switzerland

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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.

Keywords: Drug Discovery, Fungal strains, Metabolomics, antimicrobial, ESKAPE, AMR, FLECS-96

Received: 17 May 2025; Accepted: 17 Jun 2025.

Copyright: © 2025 Bory, Luscher, Lecoultre, Köhler, Schnee, Gindro and Jean-Luc. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Alexandre Jean Bory, Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU, Geneva, Switzerland
Wolfender Jean-Luc, Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU, Geneva, Switzerland

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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