Discovery and Heterologous Expression of the Soil Metagenome-Derived Lasso Peptide Metanodin with an Unprecedented Ring Structure 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.

Happy to share our newest manuscript about the discovery and hererologous expression of metanodin, a new lassopeptide with unprecedented structural features directly from soil metagenomes. pubs.acs.org/doi/full/10....
#secmet #lassopeptides #syntheticbiology

New antibiotic found in soil has potential to fight superbugs Lariocidin is a newly discovered antibiotic from soil bacteria. It targets the bacterial ribosome, defeating resistant infections.

New #antibiotic found in soil has potential to fight superbugs. The new antibiotic candidate, #lariocidin, stands out not just for its power but also for its uniqueness. It belongs to a group of natural compounds called #lassopeptides. www.earth.com/news/new-ant...

New peptide antibiotic stops bacteria by binding where no drug has before 🔬🧫💥 www.news-medical.net/news/2025032... #Antibiotics #DrugResistance #Microbiology #InfectiousDiseases #Biotech #Ribosome #Peptides #Antimicrobial #Health #LassoPeptides @nature.com