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.

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...

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...

Bacterial biosynthetic gene clusters (BGCs) drive the production of diverse bioactive specialized metabolites regulated by transcription factors (TFs) in response to environmental signals. In this met...

als Wissenschaftlerinnen und Wissenschaftler in Deutschland sind wir in großer Sorge. Die Klima­krise und weitere Umweltkrisen (Biodiversitätsverlust, Überlastung biogeochemischer Stoffkreisläu­fe ......

Streptomyces bacteria make diverse specialised metabolites that form the basis of ~55% of clinically used antibiotics. Despite this, only 3% of their encoded specialised metabolites have been matched ...