ArticleNucleic acids research2017
Co-produced natural ketolides methymycin and pikromycin inhibit bacterial growth by preventing synthesis of a limited number of proteins.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Approaches for Studying Context Specificity of Translation Inhibitor Action.International journal of molecular sciences · 2026Review
- Proteotoxic Stress Bioreporter Enables Mechanism-Informed Antibiotic Discovery.Journal of natural products · 2026Article
- Macrolide-induced hypersensitivity reactions in the pediatric population.Italian journal of pediatrics · 2026Review
- Antibiotic Mechanisms and Resistance: Molecular Insights and Therapeutic Strategies.Antibiotics (Basel, Switzerland) · 2026Review
- Structural insights into context-specific inhibition of bacterial translation by macrolides.Nature communications · 2025Article
- Macrolones target bacterial ribosomes and DNA gyrase and can evade resistance mechanisms.Nature chemical biology · 2024Article
- A Novel Class of Ribosome Modulating Agents Exploits Cancer Ribosome Heterogeneity to Selectively Target the CMS2 Subtype of Colorectal Cancer.Cancer research communications · 2023Article
- Mechanism-Based Approach to New Antibiotic Producers Screening among Actinomycetes in the Course of the Citizen Science Project.Antibiotics (Basel, Switzerland) · 2022Article
- Chemoenzymatic synthesis of fluorinated polyketides.Nature chemistry · 2022Article
- Ribosome-binding and anti-microbial studies of the mycinamicins, 16-membered macrolide antibiotics from Micromonospora griseorubida.Nucleic acids research · 2021Article
- Context-specific action of macrolide antibiotics on the eukaryotic ribosome.Nature communications · 2021Article
- Macrolides: From Toxins to Therapeutics.Toxins · 2021Review
- Structure of Erm-modified 70S ribosome reveals the mechanism of macrolide resistance.Nature chemical biology · 2021Article
- ABC-F translation factors: from antibiotic resistance to immune response.FEBS letters · 2021Review
- Translational Attenuation Mechanism ofFrontiers in microbiology · 2021Article
- Advanced Methods for Studying Structure and Interactions of Macrolide Antibiotics.International journal of molecular sciences · 2020Review
- Insights into the improved macrolide inhibitory activity from the high-resolution cryo-EM structure of dirithromycin bound to theRNA (New York, N.Y.) · 2020Article
- Structure of ribosome-bound azole-modified peptide phazolicin rationalizes its species-specific mode of bacterial translation inhibition.Nature communications · 2019Article
- ABCF ATPases Involved in Protein Synthesis, Ribosome Assembly and Antibiotic Resistance: Structural and Functional Diversification across the Tree of Life.Journal of molecular biology · 2019Article
- High-resolution crystal structures of ribosome-bound chloramphenicol and erythromycin provide the ultimate basis for their competition.RNA (New York, N.Y.) · 2019Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Antibiotics methymycin (MTM) and pikromycin (PKM), co-produced by Streptomyces venezuelae, represent minimalist macrolide protein synthesis inhibitors. Unlike other macrolides, which carry several side chains, a single desosamine sugar is attached to the macrolactone ring of MTM and PKM. In addition, the macrolactone scaffold of MTM is smaller than in other macrolides. The unusual structure of MTM and PKM and their simultaneous secretion by S. venezuelae bring about the possibility that two compounds would bind to distinct ribosomal sites. However, by combining genetic, biochemical and crystallographic studies, we demonstrate that MTM and PKM inhibit translation by binding to overlapping sites in the ribosomal exit tunnel. Strikingly, while MTM and PKM readily arrest the growth of bacteria, ∼40% of cellular proteins continue to be synthesized even at saturating concentrations of the drugs. Gel electrophoretic analysis shows that compared to other ribosomal antibiotics, MTM and PKM prevent synthesis of a smaller number of cellular polypeptides illustrating a unique mode of action of these antibiotics.
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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.