Developing a Predation-Oriented Metabolomics Pipeline to Uncover New Antibiotics from Myxobacteria

The threat of antimicrobial resistance demands the exploration of underexplored microbial resources and innovative discovery methodologies. We introduce a strategy integrating predation-oriented strain prioritization with NMR-based metabolomics to accelerate antibiotic discovery from myxobacteria. By combining ecological prioritization, chromatographic prefractionation, universal NMR fingerprinting, and chemometric deconvolution, we achieved rapid dereplication of known metabolites and selective identification of structurally intriguing molecules, including novel alkylglycosides, unusual aldoximes, and new cystobactamid derivatives. The alkylglycosides act as antibiotic adjuvants, potentiating clinical antibiotics. We further elucidate the ecological role of cystobactamids as effector molecules that enhance the predatory capability of diverse myxobacteria against various prey microbes, including phytopathogenic fungi, despite lacking antifungal activity. This integrated pipeline provides a robust framework to unlock the antibiotic potential of predatory bacteria and paves the way for next-generation agrochemical agents.