دورية أكاديمية
Mimicry of a Non-ribosomally Produced Antimicrobial, Brevicidine, by Ribosomal Synthesis and Post-translational Modification.
| العنوان: | Mimicry of a Non-ribosomally Produced Antimicrobial, Brevicidine, by Ribosomal Synthesis and Post-translational Modification. |
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| المؤلفون: | Zhao X; Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, 9747 AG Groningen, the Netherlands., Li Z; Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, 9747 AG Groningen, the Netherlands., Kuipers OP; Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, 9747 AG Groningen, the Netherlands. Electronic address: o.p.kuipers@rug.nl. |
| المصدر: | Cell chemical biology [Cell Chem Biol] 2020 Oct 15; Vol. 27 (10), pp. 1262-1271.e4. Date of Electronic Publication: 2020 Jul 23. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101676030 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2451-9448 (Electronic) Linking ISSN: 24519448 NLM ISO Abbreviation: Cell Chem Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Cambridge, MA : Cell Press, 2016- |
| مواضيع طبية MeSH: | Anti-Bacterial Agents/*pharmacology , Gram-Negative Bacteria/*drug effects , Ribosomes/*metabolism , Tyrocidine/*pharmacology, Anti-Bacterial Agents/chemistry ; Anti-Bacterial Agents/metabolism ; Hydrophobic and Hydrophilic Interactions ; Microbial Sensitivity Tests ; Protein Conformation ; Protein Processing, Post-Translational ; Tyrocidine/chemistry ; Tyrocidine/metabolism |
| مستخلص: | The group of bacterial non-ribosomally produced peptides (NRPs) forms a rich source of antibiotics, such as daptomycin, vancomycin, and teixobactin. The difficulty of functionally expressing and engineering the corresponding large biosynthetic complexes is a bottleneck in developing variants of such peptides. Here, we apply a strategy to synthesize mimics of the recently discovered antimicrobial NRP brevicidine. We mimicked the molecular structure of brevicidine by ribosomally synthesized, post-translationally modified peptide (RiPP) synthesis, introducing several relevant modifications, such as dehydration and thioether ring formation. Following this strategy, in two rounds peptides were engineered in vivo, which showed antibacterial activity against Gram-negative pathogenic bacteria susceptible to wild-type brevicidine. This study demonstrates the feasibility of a strategy to structurally and functionally mimic NRPs by employing the synthesis and post-translational modifications typical for RiPPs. This enables the future generation of large genetically encoded peptide libraries of NRP-mimicking structures to screen for antimicrobial activity against relevant pathogens. Competing Interests: Declaration of Interests The authors declare no competing interests. (Copyright © 2020 Elsevier Ltd. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Mimicry; NRPs; RiPPs; antimicrobials; biosynthetic; brevicidine; lanthipeptide |
| المشرفين على المادة: | 0 (Anti-Bacterial Agents) 0 (Tyrocidine) |
| تواريخ الأحداث: | Date Created: 20200725 Date Completed: 20210706 Latest Revision: 20210706 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.chembiol.2020.07.005 |
| PMID: | 32707039 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2451-9448 |
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| DOI: | 10.1016/j.chembiol.2020.07.005 |