Metabolomics and Molecular Networking-Guided Screening of -Derived Bioactive Compounds Against a Highly Lethal Species.

Microorganisms are important sources of bioactive natural products. However, the complexity of microbial metabolites and the low abundance of active compounds render the isolation and purification process laborious and inefficient. During our search for active substances capable of inhibiting the newly discovered highly lethal strain vp-HL, we found that the fermentation broth of multiple strains exhibited antibacterial activity. However, the substances responsible for the activity remained unclear. Metabolomics, molecular networking (MN), and the Structural similarity Network Annotation Platform for Mass Spectrometry (SNAP-MS) were employed in conjunction with bioactivity screening to predict the antibacterial compounds from strains. The analysis of fractions, and their isolation, NMR-based annotation, and bioactivity evaluation of an amicoumacin compound partially confirmed the prediction from these statistical analyses. This work presents the potential of marine in producing active substances against species. Additionally, it highlighted the significance and feasibility of metabolomics and MN in the dereplication of compounds and the determination of isolation targets.