AbstractBackground. Soil ecosystems have long been recognised as hotspots of microbial diversity, but most estimates of their microbial and functional comp

Culture-independent metagenomic approaches have proven to be effective tools for identifying previously hidden biosynthetic gene clusters (BGCs) encoding novel natural products with potential medical relevance. However, producing these compounds remains challenging as metagenomic BGCs often originate from organisms phylogenetically distant from available heterologous hosts. Lasso peptides, a subclass of ribosomally synthesized and post-translationally modified peptide (RiPP) natural products, exhibit diverse bioactivities, yet no lasso peptide has previously been discovered directly from a metagenome. Here, we report the discovery and heterologous expression of the first soil metagenome-derived lasso peptide. Expression of its biosynthetic gene cluster in Escherichia coli, followed by mass spectrometry analysis, strongly supported the predicted amino acid sequence and lasso structure of the peptide. Notably, this lasso peptide is the first to feature asparagine as the ring-forming residue at position one. Taxonomic analysis of the corresponding BGC identified an uncultivated member of the Steroidobacterales family (Gammaproteobacteria) as the closest known relative of the potential native host. These findings underscore the potential of metagenomic genome mining to reveal structurally novel RiPPs and to expand our understanding of the natural diversity of lasso peptides.

Phylogenetic analysis is widely used to predict enzyme function, yet building annotated and reusable trees is labor-intensive and requires extensive knowledge about the specific enzymes. Existing reso...

Covering: 2013 to 2023 In this review, we analyzed the scientific literature of the period 2013–2023 that reported novel specialized metabolites from the Actinomycetes, one of the most prolific…

Phylogenetic analysis is widely used to predict enzyme function, yet building annotated and reusable trees is labor-intensive and requires extensive knowledge about the specific enzymes. Existing reso...

We are excited to launch a naming competition inspired by the recent preprint "Phylogenetic distance and structural diversity directing a reclassification of glycopeptide antibiotics" (https://www.bio...

In the relentless quest to harness nature’s biochemical arsenal, researchers have pushed the boundaries of microbial engineering, uncovering novel strategies for scalable production of valuable secondary metabolites. These compounds—ranging from antibiotics to anticancer agents—are vital to medicine, agriculture, and biotechnology. Among the microbial workhorses, species of the genus Streptomyces stand out as prolific producers of these bioactive molecules. However, translating the rich secondary metabolite profiles of…

The Ziemert lab is interested in the evolution and distribution of bacterial secondary metabolites. These bioactive compounds are especially important in human medicine as the chemical scaffolds are t...

A new lasso peptide antibiotic exhibits broad-spectrum activity against Gram-negative and Gram-positive bacteria by interfering with bacterial protein synthesis, is unaffected by common resistanc...

Background Soil ecosystems have long been recognized as hotspots of microbial diversity, but most estimates of their complexity remain speculative, relying on limited data and extrapolation from shall...