ArticleNature communications2024
Rule-based omics mining reveals antimicrobial macrocyclic peptides against drug-resistant clinical isolates.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Marine Antimicrobial Peptides: From Ocean Biodiversity to Genome Mining, Multi-Omics Discovery, and Biotechnological Innovation in the Battle Against Antimicrobial Resistance.Probiotics and antimicrobial proteins · 2026Review
- Integrated Genome Mining, Bacterial Co-Culture Activation, and Peptidomic Analyses Identify Antimicrobial Peptide Candidates from South American Bacteria.Antibiotics (Basel, Switzerland) · 2026Article
- Design, synthesis, molecular docking, and antimicrobial evaluation of hybrid peptides incorporating unnatural amino acids with enhanced hydrophobic sidechains.RSC advances · 2026Article
- Pseudokinases can catalyse peptide cyclization through thioether crosslinking.Nature chemistry · 2026Article
- Recent advances in computational antimicrobial peptide discovery through big data, modeling, and artificial intelligence and their interplay in ushering the next golden era of drug development.Frontiers in bioinformatics · 2026Review
- Genome mining strategies to unlock the metabolic potential ofFrontiers in microbiology · 2026Article
- Beyond antibiotics: artificial intelligence-enabled anti-infective ecosystems for next-generation precision therapeutics against antimicrobial resistance.Frontiers in cellular and infection microbiology · 2026Article
- Systematically investigating and identifying bacteriocins in the human gut microbiome.Cell genomics · 2025Article
- Promiscuity of lanthipeptide enzymes: new challenges and applications.World journal of microbiology & biotechnology · 2025Review
- A Unique Class of Cyclases with a Kinase Fold Catalyzes Enethiol-Mediated Macrocyclization of Aminovinyl-Cysteine Motifs in Lanthipeptides.ACS central science · 2025Article
- Autoinducing peptides regulate antibiotic production to potentially shape root microbiome.Science advances · 2025Article
- Decoding the Chemical Language of Ribosomally Synthesized and Post-Translationally Modified Peptides from the Untapped Archaea Domain.Angewandte Chemie (International ed. in English) · 2025Article
- A new Clonostachys Sp. ZBS49 filamentous fungus with high production of betulinic acid and its inhibitory effect on liver cancer cells.Microbial cell factories · 2025Article
- Progress in the Identification and Design of Novel Antimicrobial Peptides Against Pathogenic Microorganisms.Probiotics and antimicrobial proteins · 2025Review
- Machine learning-guided optimization of triple agonist peptide therapeutics for metabolic disease.Frontiers in bioinformatics · 2025Article
- Cell-Free Systems: Ideal Platforms for Accelerating the Discovery and Production of Peptide-Based Antibiotics.International journal of molecular sciences · 2024Review
- Genomic Analysis of NovelMarine drugs · 2024Article
- Rule-based omics mining reveals antimicrobial macrocyclic peptides against drug-resistant clinical isolates.Nature communications · 2024Article
- Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond.Beilstein journal of organic chemistry · 2024Article
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antimicrobial resistance remains a significant global threat, driving up mortality rates worldwide. Ribosomally synthesized and post-translationally modified peptides have emerged as a promising source of novel peptide antibiotics due to their diverse chemical structures. Here, we report the discovery of new aminovinyl-(methyl)cysteine (Avi(Me)Cys)-containing peptide antibiotics through a synergistic approach combining biosynthetic rule-based omics mining and heterologous expression. We first bioinformatically identify 1172 RiPP biosynthetic gene clusters (BGCs) responsible for Avi(Me)Cys-containing peptides formation from a vast pool of over 50,000 bacterial genomes. Subsequently, we successfully establish the connection between three identified BGCs and the biosynthesis of five peptide antibiotics via biosynthetic rule-guided metabolic analysis. Notably, we discover a class V lanthipeptide, massatide A, which displays excellent activity against gram-positive pathogens, including drug-resistant clinical isolates like linezolid-resistant S. aureus and methicillin-resistant S. aureus, with a minimum inhibitory concentration of 0.25 μg/mL. The remarkable performance of massatide A in an animal infection model, coupled with a relatively low risk of resistance and favorable safety profile, positions it as a promising candidate for antibiotic development. Our study highlights the potential of Avi(Me)Cys-containing peptides in expanding the arsenal of antibiotics against multi-drug-resistant bacteria, offering promising drug leads in the ongoing battle against infectious diseases.
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