Bioactive Molecular Networking for Mapping the Antimicrobial Constituents of the Baltic Brown AlgaFucus vesiculosus

The brown algaFucus vesiculosusis common to the intertidal zones of the Baltic Sea, where it is exposed to high fouling pressures by microorganisms. Our previous studies showed, repeatedly, the consistent antimicrobial activity ofF. vesiculosuscrude extracts against human pathogens, while untargeted metabolomics analyses have revealed a variety of metabolites. In this study, we applied the UPLC-QToF-MS/MS-based "bioactive molecular networking" (BMN) concept on the most bioactiven-hexane andn-butanol subextracts of BalticF. vesiculosuscoupled with in silico dereplication tools to identify the compounds responsible for antimicrobial activity. The first antimicrobial cluster identified by BMN was galactolipids. Our targeted isolation efforts for this class led to the isolation of six monogalactosyldiacylglycerol (MGDG) derivatives (1-6) and one digalactosyldiacylglycerol (DGDG,7). The MGDGs5and6and the DGDG7exhibited activity againstStaphylococcus aureus.The second compound class with high bioactivity was phlorotannins. In particular, phlorethol-type phlorotannins showed high correlations with antimicrobial activity based on the BMN approach, and two phlorotannins (8-9) were isolated. This study shows that antimicrobial components ofF. vesiculosusreside in the algal cell walls and membranes and that BMN provides a complementary tool for the targeted isolation of bioactive metabolites.