Ribosomally derived lipopeptides containing distinct fatty acyl moieties
| Autor: | Florian Hubrich, Nina M. Bösch, Clara Chepkirui, Brandon I. Morinaka, Michael Rust, Muriel Gugger, Serina L. Robinson, Anna L. Vagstad, Jörn Piel |
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| Přispěvatelé: | Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), National University of Singapore (NUS), Collection des Cyanobactéries, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Swiss Federal Insitute of Aquatic Science and Technology [Dübendorf] (EAWAG), We are grateful for financial support (F.H. for financial support by the Vontobel Foundation, S.L.R. for financial support by the ETH Zürich Postdoctoral Fellowship [20-1 FEL-07], and J.P. for financial support by the Swiss National Science Foundation (SNSF) [National Research Program 72 'Antimicrobial resistance,' 407240_167051]). |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Antifungal Agents
Multidisciplinary N-acylation natural products [SDV]Life Sciences [q-bio] Biological Sciences Cyanobacteria Biochemistry Peptides Cyclic Anti-Bacterial Agents Biosynthetic Pathways RiPPs peptides biosynthesis Lipopeptides lipids (amino acids peptides and proteins) Peptide Synthases Ribosomes |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, 2022, 119 (3), pp.e2113120119. ⟨10.1073/pnas.2113120119⟩ Proceedings of the National Academy of Sciences of the United States of America, 119 (3) |
| ISSN: | 0027-8424 1091-6490 |
| DOI: | 10.1073/pnas.2113120119⟩ |
| Popis: | Lipopeptides represent a large group of microbial natural products that include important antibacterial and antifungal drugs and some of the most-powerful known biosurfactants. The vast majority of lipopeptides comprise cyclic peptide backbones N-terminally equipped with various fatty acyl moieties. The known compounds of this type are biosynthesized by nonribosomal peptide synthetases, giant enzyme complexes that assemble their products in a non-gene-encoded manner. Here, we report the genome-guided discovery of ribosomally derived, fatty-acylated lipopeptides, termed selidamides. Heterologous reconstitution of three pathways, two from cyanobacteria and one from an arctic, ocean-derived alphaproteobacterium, allowed structural characterization of the probable natural products and suggest that selidamides are widespread over various bacterial phyla. The identified representatives feature cyclic peptide moieties and fatty acyl units attached to (hydroxy)ornithine or lysine side chains by maturases of the GCN5-related N-acetyltransferase superfamily. In contrast to nonribosomal lipopeptides that are usually produced as congener mixtures, the three selidamides are selectively fatty acylated with C10, C12, or C16 fatty acids, respectively. These results highlight the ability of ribosomal pathways to emulate products with diverse, nonribosomal-like features and add to the biocatalytic toolbox for peptide drug improvement and targeted discovery. Proceedings of the National Academy of Sciences of the United States of America, 119 (3) ISSN:0027-8424 ISSN:1091-6490 |
| Databáze: | OpenAIRE |
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