ArticleChemistry & biology2014
Lassomycin, a ribosomally synthesized cyclic peptide, kills mycobacterium tuberculosis by targeting the ATP-dependent protease ClpC1P1P2.
Article in Chemistry & biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 200 papers, 1 of them a synthesis that pooled it.
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Who cites it
200 citing papers in PubMed, 1 synthesis or guideline pooled it, 426 citations in OpenAlex.
- Advancements in the Application of Ribosomally Synthesized and Post-Translationally Modified Peptides (RiPPs).Biomolecules · 2024Pooled it
- Small-molecule activators of theiScience · 2026Article
- Microbial Natural Products Targeting theMicroorganisms · 2026Review
- Antimicrobial peptides for tuberculosis in a post-antibiotic era: from in vitro promise to therapeutic potential.npj antimicrobials and resistance · 2026Review
- ClpC1-dependent iron homeostasis underlies mycobacterial defense against oxygen-driven Fenton reaction during reactivation.Microbiology spectrum · 2026Article
- Tangled Tail of Mechanically Interlocked Peptides.Journal of the American Chemical Society · 2026Review
- Peptide-Based Pseudo[2]- and [3]rotaxanes Assembled via Square-Planar Palladium Coordination.ChemPlusChem · 2026Article
- Biosynthesis, Structure, and Antibiotic Properties of Gelatinamin A, a Triculamin-Like Lasso Peptide.Chembiochem : a European journal of chemical biology · 2026Article
- Proteostasis-targeted antibacterial strategies.Journal of microbiology (Seoul, Korea) · 2026Review
- ClpC1-targeting peptide natural products differentially dysregulate the proteome of Mycobacterium tuberculosis.Nature communications · 2026Article
- Dual-probe genome mining identifies citrulassin N, a novel citrulline modified lasso peptide fromFrontiers in microbiology · 2026Article
- Advancing Tuberculosis Chemotherapy: Targeted Nanomedicines for the Mycobacterium TB Granuloma.Small (Weinheim an der Bergstrasse, Germany) · 2025Review
- Allosteric control of the bacterial ClpC/ClpP protease and its hijacking by antibacterial peptides.The EMBO journal · 2025Article
- Mining Microbial Dark Matter: Advanced Cultivation Techniques for Bioactive Compound Discovery.Pharmaceuticals (Basel, Switzerland) · 2025Review
- An integrated multi-omic approach for discovery and dereplication of bioactive microbial natural products.Microbial genomics · 2025Article
- Natural Products with Potent Antimycobacterial Activity (2000-2024): A Review.Molecules (Basel, Switzerland) · 2025Review
- A chlorinated diketopiperazine antibiotic targetsAntimicrobial agents and chemotherapy · 2025Article
- Allosteric regulation of proteolytic machines unveiled by the synergy between cryo-EM and solution NMR spectroscopy.The Biochemical journal · 2025Review
- Lasso Peptides-A New Weapon Against Superbugs.International journal of molecular sciences · 2025Review
- Systematic Determination of the Impact of Structural Edits on Peptide Accumulation into Mycobacteria.ACS chemical biology · 2025Article
140 more citing papers are in PubMed but not listed here.
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17 authors at 3 institutions in 1 country.
Funding
Abstract
Languishing antibiotic discovery and flourishing antibiotic resistance have prompted the development of alternative untapped sources for antibiotic discovery, including previously uncultured bacteria. Here, we screen extracts from uncultured species against Mycobacterium tuberculosis and identify lassomycin, an antibiotic that exhibits potent bactericidal activity against both growing and dormant mycobacteria, including drug-resistant forms of M. tuberculosis, but little activity against other bacteria or mammalian cells. Lassomycin is a highly basic, ribosomally encoded cyclic peptide with an unusual structural fold that only partially resembles that of other lasso peptides. We show that lassomycin binds to a highly acidic region of the ClpC1 ATPase complex and markedly stimulates its ATPase activity without stimulating ClpP1P2-catalyzed protein breakdown, which is essential for viability of mycobacteria. This mechanism, uncoupling ATPase from proteolytic activity, accounts for the bactericidal activity of lassomycin.
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Registered trials
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.