A big challenge in natural product research of today is rapid identification and exclusion of already known substances to free capacities for the exploration of new agents. Prompt information on bioactivities and mode of action (MOA) is required for rational compound optimization.
In a collaborative project between scientists from the research group of Heike Brötz-Oesterhelt at the University of Tübingen and the research group of Yvonne Mast at the DSMZ, a bioreporter approach has been developed, which allows for combined bioactivity- and MOA-informed primary screening for antimicrobials. The study was mainly supported by the German Center of Infection Research (DZIF).
The bioreporter approach allows MOA-informed primary screening of bioactive compounds produced by a given strain without the need for initial compound enrichment or purification. The method is cost-effective, straightforward, and applicable along the entire purification pipeline. It works well with producer strains grown on agar, culture supernatants, extracts, fractions, and pure substances. In combination with chemical analytics like high-resolution mass spectrometry, the biosensor panel is an efficient and sensitive tool for compound deconvolution.
The bioreporter approach also detects when a producer strain synthesizes more than one antibiotic or if a single agent has more than one MOA. It immediately informs about the metabolic pathway inhibited, enabling the selection of focused follow-up assays to elucidate the molecular target.
Wex K W, Saur J S, Handel F, Ortlieb N, Mokeev V, Kulik A, Niedermeyer T H J, Mast Y, Grond S, Berscheid A, Brötz-Oesterhelt H.
Bioreporters for direct mode of action-informed screening of antibiotic producer strains.
CellChemBio (2021), doi: 10.1016/j.chembiol.2021.02.022.