Abstract
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 of new compounds and may broaden application options when additional targets of known agents are uncovered. Here, we present a bioreporter assay setup as a versatile strategy for combined bioactivity- and MOA-guided primary screening for antibacterial agents. The approach is suitable for directly probing producer strains grown on agar, without need for initial compound enrichment or purification. The application works well along the entire purification pipeline with culture supernatants, extracts, fractions, and pure substances. The biosensors allow for a MOA-guided purification to selectively prioritize metabolic activities of interest. In combination with high-resolution mass spectrometry, the technology is a highly efficient and sensitive tool for rapid compound identification and target deconvolution.
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