ArticleAngewandte Chemie (International ed. in English)2021
Biosynthesis and Mechanism of Action of the Cell Wall Targeting Antibiotic Hypeptin.
Article in Angewandte Chemie (International ed. in English), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 36 citations in OpenAlex.
- A Siderophore-Antibiotic Heterodimer Imaging Agent EnablesJournal of medicinal chemistry · 2026Article
- RECC: A Red/ET-CRISPR/Cas9-based system enabling genome mining of marineSynthetic and systems biotechnology · 2026Article
- Genomic Features of the MicropredatorInternational journal of molecular sciences · 2026Article
- Comparative Analysis of Signature Sequences from Adenylation Domains Situated within Bacterial-Origin Nonribosomal Peptide Synthetase Modules.Journal of microbiology and biotechnology · 2025Article
- Assessing Normandy Soil Microbial Diversity for Antibacterial Activities Using Traditional Culture and iChip Methods.Microorganisms · 2024Article
- Genome sequencing and mining expand the naturalproduct repertoire of Lysobacter.Research square · 2024Article
- Real-Time Biosynthetic Reaction Monitoring Informs the Mechanism of Action of Antibiotics.Journal of the American Chemical Society · 2024Article
- Genetic Basis and Expression Pattern Indicate the Biocontrol Potential and Soil Adaption ofMicroorganisms · 2023Article
- A new antibiotic from an uncultured bacterium binds to an immutable target.bioRxiv : the preprint server for biology · 2023Article
- Modern Trends in Natural Antibiotic Discovery.Life (Basel, Switzerland) · 2023Review
- Synthesis and Stereochemical Determination of the Peptide Antibiotic Novo29.The Journal of organic chemistry · 2023Article
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- Linearized teixobactin is inactive and after sequence enhancement, kills methicillin-resistant Staphylococcus aureus via a different mechanism.Peptide science (Hoboken, N.J.) · 2022Article
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- Beyond Soil-Dwelling Actinobacteria: Fantastic Antibiotics and Where to Find Them.Antibiotics (Basel, Switzerland) · 2022Review
- Scalable and Selective β-Hydroxy-α-Amino Acid Synthesis Catalyzed by Promiscuous l-Threonine Transaldolase ObiH.Chembiochem : a European journal of chemical biology · 2022Article
- THCz: Small molecules with antimicrobial activity that block cell wall lipid intermediates.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Biosynthesis and Mechanism of Action of the Cell Wall Targeting Antibiotic Hypeptin.Angewandte Chemie (International ed. in English) · 2021Article
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
Abstract
Hypeptin is a cyclodepsipeptide antibiotic produced by Lysobacter sp. K5869, isolated from an environmental sample by the iChip technology, dedicated to the cultivation of previously uncultured microorganisms. Hypeptin shares structural features with teixobactin and exhibits potent activity against a broad spectrum of gram-positive pathogens. Using comprehensive in vivo and in vitro analyses, we show that hypeptin blocks bacterial cell wall biosynthesis by binding to multiple undecaprenyl pyrophosphate-containing biosynthesis intermediates, forming a stoichiometric 2:1 complex. Resistance to hypeptin did not readily develop in vitro. Analysis of the hypeptin biosynthetic gene cluster (BGC) supported a model for the synthesis of the octapeptide. Within the BGC, two hydroxylases were identified and characterized, responsible for the stereoselective β-hydroxylation of four building blocks when bound to peptidyl carrier proteins. In vitro hydroxylation assays corroborate the biosynthetic hypothesis and lead to the proposal of a refined structure for hypeptin.
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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.