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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ftpubmed:oai:pubmedcentral.nih.gov:8784127 2023-05-15T15:06:35+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 2022-01-13 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8784127/ http://www.ncbi.nlm.nih.gov/pubmed/35027450 https://doi.org/10.1073/pnas.2113120119 en eng National Academy of Sciences http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8784127/ http://www.ncbi.nlm.nih.gov/pubmed/35027450 http://dx.doi.org/10.1073/pnas.2113120119 Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . CC-BY-NC-ND Proc Natl Acad Sci U S A Biological Sciences Text 2022 ftpubmed https://doi.org/10.1073/pnas.2113120119 2022-02-06T01:49:26Z 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 C(10), C(12), or C(16) 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. Text Arctic Arctic Ocean PubMed Central (PMC) Arctic Arctic Ocean Proceedings of the National Academy of Sciences 119 3 |
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English |
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Biological Sciences |
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Biological Sciences 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 |
Biological Sciences |
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 C(10), C(12), or C(16) 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. |
format |
Text |
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 |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8784127/ http://www.ncbi.nlm.nih.gov/pubmed/35027450 https://doi.org/10.1073/pnas.2113120119 |
geographic |
Arctic Arctic Ocean |
geographic_facet |
Arctic Arctic Ocean |
genre |
Arctic Arctic Ocean |
genre_facet |
Arctic Arctic Ocean |
op_source |
Proc Natl Acad Sci U S A |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8784127/ http://www.ncbi.nlm.nih.gov/pubmed/35027450 http://dx.doi.org/10.1073/pnas.2113120119 |
op_rights |
Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
op_rightsnorm |
CC-BY-NC-ND |
op_doi |
https://doi.org/10.1073/pnas.2113120119 |
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Proceedings of the National Academy of Sciences |
container_volume |
119 |
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3 |
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1766338157345767424 |