ArticleNature communications2023
Resurrecting ancestral antibiotics: unveiling the origins of modern lipid II targeting glycopeptides.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 35 citations in OpenAlex.
- Synthesis of Glycopeptide Antibiotic Peptide Substrates Using Knorr-Pyrazole Chemistry.ChemMedChem · 2026Article
- Evolutionary strategies of late-stage diversification in bacterial biosynthetic gene clusters.Essays in biochemistry · 2026Review
- DiscERN: an automated genome mining tool for the discovery of evolutionarily related natural products.Nature communications · 2026Article
- PhyloNaP: a user-friendly database of phylogeny for natural product-producing enzymes.Bioinformatics (Oxford, England) · 2026Article
- Investigating the P450-Mediated Cross-Linking of the Atypical GPA Complestatin Using Alternate Peptide Probes.The Journal of organic chemistry · 2026Article
- Molecular war and peace: the concurrent path to antibiosis and antibiotic resistance.Frontiers in microbiology · 2026Review
- Molecular Paleontology Meets Drug Discovery: The Case for De-extinct Antimicrobials.ACS omega · 2025Review
- Mobilome-mediated transcriptional activation of biosynthetic gene clusters and its impact on strain competitiveness in food fermentation microbiomes.Microbiome · 2025Article
- Mixing and Matching of Hybrid Megasynthases is a Hub for the Evolution of Metabolic Diversity in Cyanobacteria.Angewandte Chemie (International ed. in English) · 2025Article
- Teicoplanin Nonribosomal Peptide Synthetase Is Unable to Incorporate Alpha-Ketoacid Building Blocks.Biochemistry · 2025Article
- A rare peptide scaffold in kineomicins, the glycopeptide antibiotics produced by Actinokineospora auranticolor DSM 44650.Communications chemistry · 2025Article
- Unveiling the substrate specificity of the ABC transporter Tba and its role in glycopeptide biosynthesis.iScience · 2025Article
- Complete Genome Assembly ofGenes · 2024Article
- Biosynthesis of a clickable pyoverdine via in vivo enzyme engineering of an adenylation domain.Microbial cell factories · 2024Article
- Structural, biochemical and bioinformatic analyses of nonribosomal peptide synthetase adenylation domains.Natural product reports · 2024Review
- Accessing microbial natural products of the past.microLife · 2024Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Antibiotics are central to modern medicine, and yet they are mainly the products of intra and inter-kingdom evolutionary warfare. To understand how nature evolves antibiotics around a common mechanism of action, we investigated the origins of an extremely valuable class of compounds, lipid II targeting glycopeptide antibiotics (GPAs, exemplified by teicoplanin and vancomycin), which are used as last resort for the treatment of antibiotic resistant bacterial infections. Using a molecule-centred approach and computational techniques, we first predicted the nonribosomal peptide synthetase assembly line of paleomycin, the ancestral parent of lipid II targeting GPAs. Subsequently, we employed synthetic biology techniques to produce the predicted peptide and validated its antibiotic activity. We revealed the structure of paleomycin, which enabled us to address how nature morphs a peptide antibiotic scaffold through evolution. In doing so, we obtained temporal snapshots of key selection domains in nonribosomal peptide synthesis during the biosynthetic journey from ancestral, teicoplanin-like GPAs to modern GPAs such as vancomycin. Our study demonstrates the synergy of computational techniques and synthetic biology approaches enabling us to journey back in time, trace the temporal evolution of antibiotics, and revive these ancestral molecules. It also reveals the optimisation strategies nature has applied to evolve modern GPAs, laying the foundation for future efforts to engineer this important class of antimicrobial agents.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.