Ribosomally derived lipopeptides containing distinct fatty acyl moieties
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....
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ftethz:oai:www.research-collection.ethz.ch:20.500.11850/529017 2023-05-15T15:07:10+02:00 Ribosomally derived lipopeptides containing distinct fatty acyl moieties Hubrich, Florian Bösch, Nina M. Chepkirui, Clara Morinaka, Brandon I. Rust, Michael Gugger, Muriel Robinson, Serina L. Vagstad, Anna L. Piel, Jörn 2022-01-18 application/application/pdf https://hdl.handle.net/20.500.11850/529017 https://doi.org/10.3929/ethz-b-000529017 en eng National Academy of Sciences info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.2113120119 info:eu-repo/semantics/altIdentifier/wos/000748781000011 info:eu-repo/grantAgreement/SNF/NFP 72: Gesuch/167051 http://hdl.handle.net/20.500.11850/529017 doi:10.3929/ethz-b-000529017 info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/4.0/ Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International CC-BY-NC-ND Proceedings of the National Academy of Sciences of the United States of America, 119 (3) RiPPs natural products peptides N-acylation biosynthesis info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 2022 ftethz https://doi.org/20.500.11850/529017 https://doi.org/10.3929/ethz-b-000529017 https://doi.org/10.1073/pnas.2113120119 2023-02-13T01:02:42Z 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. ISSN:0027-8424 ISSN:1091-6490 Article in Journal/Newspaper Arctic Arctic Ocean ETH Zürich Research Collection Arctic Arctic Ocean |
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Open Polar |
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ETH Zürich Research Collection |
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language |
English |
topic |
RiPPs natural products peptides N-acylation biosynthesis |
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RiPPs natural products peptides N-acylation biosynthesis Hubrich, Florian Bösch, Nina M. Chepkirui, Clara Morinaka, Brandon I. Rust, Michael Gugger, Muriel Robinson, Serina L. Vagstad, Anna L. Piel, Jörn Ribosomally derived lipopeptides containing distinct fatty acyl moieties |
topic_facet |
RiPPs natural products peptides N-acylation biosynthesis |
description |
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. ISSN:0027-8424 ISSN:1091-6490 |
format |
Article in Journal/Newspaper |
author |
Hubrich, Florian Bösch, Nina M. Chepkirui, Clara Morinaka, Brandon I. Rust, Michael Gugger, Muriel Robinson, Serina L. Vagstad, Anna L. Piel, Jörn |
author_facet |
Hubrich, Florian Bösch, Nina M. Chepkirui, Clara Morinaka, Brandon I. Rust, Michael Gugger, Muriel Robinson, Serina L. Vagstad, Anna L. Piel, Jörn |
author_sort |
Hubrich, Florian |
title |
Ribosomally derived lipopeptides containing distinct fatty acyl moieties |
title_short |
Ribosomally derived lipopeptides containing distinct fatty acyl moieties |
title_full |
Ribosomally derived lipopeptides containing distinct fatty acyl moieties |
title_fullStr |
Ribosomally derived lipopeptides containing distinct fatty acyl moieties |
title_full_unstemmed |
Ribosomally derived lipopeptides containing distinct fatty acyl moieties |
title_sort |
ribosomally derived lipopeptides containing distinct fatty acyl moieties |
publisher |
National Academy of Sciences |
publishDate |
2022 |
url |
https://hdl.handle.net/20.500.11850/529017 https://doi.org/10.3929/ethz-b-000529017 |
geographic |
Arctic Arctic Ocean |
geographic_facet |
Arctic Arctic Ocean |
genre |
Arctic Arctic Ocean |
genre_facet |
Arctic Arctic Ocean |
op_source |
Proceedings of the National Academy of Sciences of the United States of America, 119 (3) |
op_relation |
info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.2113120119 info:eu-repo/semantics/altIdentifier/wos/000748781000011 info:eu-repo/grantAgreement/SNF/NFP 72: Gesuch/167051 http://hdl.handle.net/20.500.11850/529017 doi:10.3929/ethz-b-000529017 |
op_rights |
info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/4.0/ Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International |
op_rightsnorm |
CC-BY-NC-ND |
op_doi |
https://doi.org/20.500.11850/529017 https://doi.org/10.3929/ethz-b-000529017 https://doi.org/10.1073/pnas.2113120119 |
_version_ |
1766338728713781248 |