Work

Accelerating the Discovery of Marine Natural Products with Antimicrobial activity via Bioactivity-Driven Molecular Networking

Year: 2026

Type: preprint

Abstract: The growing threat of antimicrobial resistance underscores an urgent need to investigate underexplored natural sources to provide new chemical scaffolds for drug development. Marine environments, particularly those along the South African coastline, represent reservoirs of novel chemical diversity with the potential to provide new classes of antibiotics. This study reports the development of an efficient biodiscovery pipeline for the assembly and systematic screening of marine natural products extract libraries to identify novel antimicrobial leads. The workflow integrates microbial genomics and biological screening with non-targeted high resolution tandem mass spectrometry and molecular networking. Chemical extracts of 174 sponges and tunicates collected from the South African coast were evaluated for antibacterial, cytotoxic, and in vitro enzyme inhibitory activity. Guided by molecular networkbased feature prioritization, eleven known secondary metabolites spanning four major 2 structural classes (bifunctional sphingolipids, variabilin furanosesterterpenes, topsentin bisindole and pyrrolo iminoquinone -alkaloids) were isolated. The bioactivity of the isolated compounds was consistent with their corresponding crude extracts. Computational mass spectrometry analysis of extracts with antimicrobial activity revealed additional enriched metabolite families warranting further investigation. Finally, we profiled the taxonomic diversity of sponge associated bacterial communities to assess their utility in facilitating dereplication and prioritization of species of interest for further study.

Source: ChemRxiv

DOI: 10.26434/chemrxiv.15009629/v1