Human health is greatly influenced by the gut microbiota and microbiota imbalance can lead to the development of diseases. It is widely acknowledged that the interaction of bacteria within competitive ecosystems is influenced by their specialized metabolites, which act, e.g., as antibacterials or siderophores. However, our understanding of the occurrence and impact of such natural products in the human gut microbiome remains very limited. As arylthiazole siderophores are an emerging family of growth-promoting molecules in pathogenic bacteria, we analyzed a metagenomic data set from the human microbiome and thereby identified the bil-BGC, which originates from an uncultured Bilophila strain. Through gene synthesis and BGC assembly, heterologous expression and mutasynthetic experiments, we discovered the arylthiazole natural products bilothiazoles A–F. While established activities of related molecules indicate their involvement in metal-binding and -uptake, which could promote the growth of pathogenic strains, we also found antibiotic activity for some bilothiazoles. This is supported by biosensor-experiments, where bilothiazoles C and E show PrecA-suppressing activity, while bilothiazole F induces PblaZ, a biosensor characteristic for β-lactam antibiotics. These findings serve as a starting point for investigating the role of bilothiazoles in the pathogenicity of Bilophila species in the gut.

Polycyclic tetramate macrolactams (PoTeMs) derive from ornithine-based lysobacterene A. To expand the PoTeM core structure carbon skeleton by a CH2-unit, a synthetic access to lysobacterene A and an ...

Team um den neuen HIPS-Abteilungsleiter Tobias Gulder entwickelt innovative Synthesestrategien für vielversprechende Naturstoffe

Vanadium-dependent haloperoxidases (VHPOs) are versatile enzymes that catalyze oxidation of halides followed by halogenation of electron-rich substrates, but the factors dictating substrate and haloge...