ToGuLab

Heterologous Expression of a Cryptic BGC from Bilophila sp. Provides Access to a Novel Family of Antibacterial Thiazoles 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.

In February, we reported "Heterologous Expression of a Cryptic BGC from Bilophila sp. Provides Access to a Novel Family of Antibacterial Thiazoles". This full journey from bioinformatics via heterologous expression & mutasynthetic studies to new NPs is available here: pubs.acs.org/doi/10.1021/...

Today we had very special visitors: a TV-team from KBS (Korean Broadcasting System) was at HIPS. Tobias Gulder gave an Interview and shared insights to our work. We appreciate the interest and the possibility to show our research this way and are excited to see the result at the end of October!

Expanding Polycyclic Tetramate Macrolactam (PoTeM) Core Structure Diversity by Chemo‐Enzymatic Synthesis and Bioengineering 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 ...

The year started with Sebastian’s paper on the substrate promiscuity of the cyclization enzymes IkaBC. The paper includes chemical synthesis combined with exciting chemo-enzymatic transformations generating a plug-and-play system for PoTeMs. Check it out!
onlinelibrary.wiley.com/doi/10.1002/...

The Gulder group at the Castle of Saarbrücken.

The Gulder group has started its work at HIPS Saarbrücken! Since 01. August the full group is here and working in the old HIPS building as our new building is still under construction. In the coming weeks we will update you on what has happened throughout 2025 regarding our research! Stay tuned

Chemie trifft Biologie: Zugang zu neuen Naturstoffen Team um den neuen HIPS-Abteilungsleiter Tobias Gulder entwickelt innovative Synthesestrategien für vielversprechende Naturstoffe

#Naturstoffe decken ein breites Spektrum biologischer Aktivitäten ab, sind aber aufwendig herzustellen. Ein Team um @togulab.bsky.social @helmholtzhips.bsky.social zeigt in drei Publikationen neue innovative Synthesestrategien für vielversprechende Naturstoffe.
www.helmholtz-hzi.de/media-center...

Unraveling the molecular basis of substrate specificity and halogen activation in vanadium-dependent haloperoxidases - Nature Communications 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...

What is responsible for the halogen specificity & is there a Substrate binding Site in #VHPOs? Learn more about this amazing enzyme class in our latest paper @naturecomms.bsky.social Congratulations to the Team! www.nature.com/articles/s41...

Hi Kate - would be great to get included :-)

Fingers crossed - good luck!