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Nine Post-translational Modifications during the Biosynthesis of Cinnamycin
[Image: see text] Lantibiotics are ribosomally synthesized and post-translationally modified antimicrobial peptides that are characterized by the thioether cross-linked amino acids lanthionine (Lan) and methyllanthionine (MeLan). Cinnamycin is a 19 amino acid lantibiotic that contains one Lan and tw...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3163434/ https://www.ncbi.nlm.nih.gov/pubmed/21770392 http://dx.doi.org/10.1021/ja205783f |
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author | Ökesli, Ayşe Cooper, Lisa E. Fogle, Emily J. van der Donk, Wilfred A. |
author_facet | Ökesli, Ayşe Cooper, Lisa E. Fogle, Emily J. van der Donk, Wilfred A. |
author_sort | Ökesli, Ayşe |
collection | PubMed |
description | [Image: see text] Lantibiotics are ribosomally synthesized and post-translationally modified antimicrobial peptides that are characterized by the thioether cross-linked amino acids lanthionine (Lan) and methyllanthionine (MeLan). Cinnamycin is a 19 amino acid lantibiotic that contains one Lan and two MeLan. Cinnamycin also contains an unusual lysinoalanine (Lal) bridge formed from the ε-amino group of lysine 19 and a serine residue at position 6, and an erythro-3-hydroxy-l-aspartic acid resulting from the hydroxylation of l-aspartate at position 15. These modifications are critical in mediating the interactions of cinnamycin with its target, phosphatidylethanolamine. Recently, the cinnamycin biosynthetic gene cluster (cin) from Streptomyces cinnamoneus cinnamoneus DSM 40005 was reported. Herein, we investigated the biosynthetic machinery using both in vitro studies and heterologous expression in Escherichia coli. CinX is an α-ketoglutarate/iron(II)-dependent hydroxylase that carries out the hydroxylation of aspartate 15 of the precursor peptide CinA. In addition, CinM catalyzes dehydration of four Ser and Thr residues and subsequent cyclization of Cys residues to form the three (Me)Lan bridges. The order of the post-translational modifications catalyzed by CinM and CinX is interchangeable in vitro. CinX did not require the leader sequence at the N-terminus of CinA for activity, but the leader peptide was necessary for CinM function. Although CinM dehydrated serine 6, it did not catalyze the formation of Lal. A small protein encoded by cinorf7 is critical for the formation of the cross-link between Lys19 and dehydroalanine 6 as shown by coexpression studies of CinA, CinM, CinX, and Cinorf7 in E. coli. |
format | Online Article Text |
id | pubmed-3163434 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-31634342011-08-29 Nine Post-translational Modifications during the Biosynthesis of Cinnamycin Ökesli, Ayşe Cooper, Lisa E. Fogle, Emily J. van der Donk, Wilfred A. J Am Chem Soc [Image: see text] Lantibiotics are ribosomally synthesized and post-translationally modified antimicrobial peptides that are characterized by the thioether cross-linked amino acids lanthionine (Lan) and methyllanthionine (MeLan). Cinnamycin is a 19 amino acid lantibiotic that contains one Lan and two MeLan. Cinnamycin also contains an unusual lysinoalanine (Lal) bridge formed from the ε-amino group of lysine 19 and a serine residue at position 6, and an erythro-3-hydroxy-l-aspartic acid resulting from the hydroxylation of l-aspartate at position 15. These modifications are critical in mediating the interactions of cinnamycin with its target, phosphatidylethanolamine. Recently, the cinnamycin biosynthetic gene cluster (cin) from Streptomyces cinnamoneus cinnamoneus DSM 40005 was reported. Herein, we investigated the biosynthetic machinery using both in vitro studies and heterologous expression in Escherichia coli. CinX is an α-ketoglutarate/iron(II)-dependent hydroxylase that carries out the hydroxylation of aspartate 15 of the precursor peptide CinA. In addition, CinM catalyzes dehydration of four Ser and Thr residues and subsequent cyclization of Cys residues to form the three (Me)Lan bridges. The order of the post-translational modifications catalyzed by CinM and CinX is interchangeable in vitro. CinX did not require the leader sequence at the N-terminus of CinA for activity, but the leader peptide was necessary for CinM function. Although CinM dehydrated serine 6, it did not catalyze the formation of Lal. A small protein encoded by cinorf7 is critical for the formation of the cross-link between Lys19 and dehydroalanine 6 as shown by coexpression studies of CinA, CinM, CinX, and Cinorf7 in E. coli. American Chemical Society 2011-07-19 2011-08-31 /pmc/articles/PMC3163434/ /pubmed/21770392 http://dx.doi.org/10.1021/ja205783f Text en Copyright © 2011 American Chemical Society http://pubs.acs.org This is an open-access article distributed under the ACS AuthorChoice Terms & Conditions. Any use of this article, must conform to the terms of that license which are available at http://pubs.acs.org. |
spellingShingle | Ökesli, Ayşe Cooper, Lisa E. Fogle, Emily J. van der Donk, Wilfred A. Nine Post-translational Modifications during the Biosynthesis of Cinnamycin |
title | Nine Post-translational Modifications during the Biosynthesis of Cinnamycin |
title_full | Nine Post-translational Modifications during the Biosynthesis of Cinnamycin |
title_fullStr | Nine Post-translational Modifications during the Biosynthesis of Cinnamycin |
title_full_unstemmed | Nine Post-translational Modifications during the Biosynthesis of Cinnamycin |
title_short | Nine Post-translational Modifications during the Biosynthesis of Cinnamycin |
title_sort | nine post-translational modifications during the biosynthesis of cinnamycin |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3163434/ https://www.ncbi.nlm.nih.gov/pubmed/21770392 http://dx.doi.org/10.1021/ja205783f |
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