Bioreporters for direct mode of action-informed screening of antibiotic producer strains
| Autor: | Anne Berscheid, Timo H. J. Niedermeyer, Yvonne Mast, Andreas Kulik, Franziska Handel, Heike Brötz-Oesterhelt, Katharina W. Wex, Vladislav Mokeev, Stephanie Grond, Julian S. Saur, Nico Ortlieb |
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| Rok vydání: | 2021 |
| Předmět: |
medicine.drug_class
Clinical Biochemistry Antibiotics Biosensing Techniques Microbial Sensitivity Tests Biology 01 natural sciences Biochemistry Mass Spectrometry Drug Discovery Escherichia coli medicine Mode of action Molecular Biology Pharmacology Biological Products 010405 organic chemistry Anti-Bacterial Agents 0104 chemical sciences Molecular targets Molecular Medicine Cell culture supernatant Bioreporter Biochemical engineering Natural Product Research Bacillus subtilis Primary screening |
| Zdroj: | Cell Chemical Biology. 28:1242-1252.e4 |
| ISSN: | 2451-9456 |
| Popis: | A big challenge in natural product research of today is rapid dereplication of already known substances, to free capacities for the exploration of new agents. Prompt information on bioactivities and mode of action (MOA) speeds up the lead discovery process and is required for rational compound optimization. Here, we present a bioreporter approach as a versatile strategy for combined bioactivity- and MOA-informed primary screening for antimicrobials. The approach is suitable for directly probing producer strains grown on agar, without need for initial compound enrichment or purification, and works along the entire purification pipeline with culture supernatants, extracts, fractions, and pure substances. The technology allows for MOA-informed purification to selectively prioritize activities of interest. In combination with high-resolution mass spectrometry, the biosensor panel is an efficient and sensitive tool for compound deconvolution. Concomitant information on the affected metabolic pathway enables the selection of appropriate follow-up assays to elucidate the molecular target. |
| Databáze: | OpenAIRE |
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