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.

The ACS Division of Organic Chemistry is pleased to announce that Professor Dean J. Tantillo (University of California, Davis) has been selected as the 2025 Leete Awardee. Established in 1995, the Leete Award recognizes outstanding contributions to teaching and research in Organic Chemistry. The award honors Edward Leete of the University of Minnesota, who, through … Read More

Grayson et al. report the genomic discovery and biochemical characterization of a widely distributed gene cluster family for briarane diterpenoid biosynthesis in metazoans. This study expands our unde...

The Scientific Council of the European Research Council welcomes the offer of substantial additional budget from the European Commission for the development of a new ERC funding instrument offering la...

Gene editing and many other useful biotechnology tools came from studies of bacteria fighting off viral invaders. But scientists have only begun to unlock the secrets of this ancient arms race.

A novel family of antibiotics, MDN-0057 to MDN-0060 (1–4), was isolated from liquid cultures of the fungus Ophiosphaerella korrae. These compounds incorporate two isocyanide groups in their complex structures that were elucidated by extensive spectroscopic analyses, including HRESIMS, and 1D and 2D NMR experiments. The relative configurations were determined by using J-based configuration analyses and the interpretation of key NOESY correlations consistent with the existence of a major conformation in solution. Mosher ester derivatization analysis allowed the establishment of their absolute configurations. All four compounds displayed in vitro antibacterial activity with a broad spectrum against Gram-negative pathogens.

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Tambjamines are complex bipyrrole-containing natural products that possess promising bioactive properties. Although Pseudoalteromonas citrea is known to produce both cyclic tambjamine MYP1 and the linear precursor (YP1), the biosynthetic machinery used to catalyze the site-selective oxidative carbocyclization at the unactivated 1° carbon of YP1 has remained unclear. Here, we demonstrate that a three-component Rieske system consisting of an oxygenase (TamC) and two redox partner proteins is responsible for this unprecedented activity on YP1 and potentially, a non-native substrate (BE-18591). We also show that a homologous oxidase from Pseudoalteromonas tunicata (PtTamC) can function together with the partner proteins from P. citrea to process both YP1 and BE-18591. These reactions represent the first Rieske oxygenase-catalyzed activations of C–H bonds at 1° carbons, resulting in carbon–carbon bond formation. The use of TamC and PtTamC to potentially generate the new-to-nature cyclic analogue of BE-18591 suggests the enormous biocatalytic potential of these Rieske systems to facilitate late-stage oxidative cyclizations at terminal C(sp3)–H bonds.

Für seine Forschung zu neuen Medikamenten gegen multiresistente Bakterien zeichnen ...