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New Deferoxamine Glycoconjugates Produced upon Overexpression of Pathway-Specific Regulatory Gene in the Marine Sponge-Derived Streptomyces albus PVA94-07

Activation of silent biosynthetic gene clusters in Streptomyces bacteria via overexpression of cluster-specific regulatory genes is a promising strategy for the discovery of novel bioactive secondary metabolites. This approach was used in an attempt to activate a cryptic gene cluster in a marine spo...

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Autores principales: Sekurova, Olga N., Pérez-Victoria, Ignacio, Martín, Jesús, Degnes, Kristin F., Sletta, Håvard, Reyes, Fernando, Zotchev, Sergey B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273380/
https://www.ncbi.nlm.nih.gov/pubmed/27618884
http://dx.doi.org/10.3390/molecules21091131
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author Sekurova, Olga N.
Pérez-Victoria, Ignacio
Martín, Jesús
Degnes, Kristin F.
Sletta, Håvard
Reyes, Fernando
Zotchev, Sergey B.
author_facet Sekurova, Olga N.
Pérez-Victoria, Ignacio
Martín, Jesús
Degnes, Kristin F.
Sletta, Håvard
Reyes, Fernando
Zotchev, Sergey B.
author_sort Sekurova, Olga N.
collection PubMed
description Activation of silent biosynthetic gene clusters in Streptomyces bacteria via overexpression of cluster-specific regulatory genes is a promising strategy for the discovery of novel bioactive secondary metabolites. This approach was used in an attempt to activate a cryptic gene cluster in a marine sponge-derived Streptomyces albus PVA94-07 presumably governing the biosynthesis of peptide-based secondary metabolites. While no new peptide-based metabolites were detected in the recombinant strain, it was shown to produce at least four new analogues of deferoxamine with additional acyl and sugar moieties, for which chemical structures were fully elucidated. Biological activity tests of two of the new deferoxamine analogues revealed weak activity against Escherichia coli. The gene knockout experiment in the gene cluster targeted for activation, as well as overexpression of certain genes from this cluster did not have an effect on the production of these compounds by the strain overexpressing the regulator. It seems plausible that the production of such compounds is a response to stress imposed by the production of an as-yet unidentified metabolite specified by the cryptic cluster.
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spelling pubmed-62733802018-12-28 New Deferoxamine Glycoconjugates Produced upon Overexpression of Pathway-Specific Regulatory Gene in the Marine Sponge-Derived Streptomyces albus PVA94-07 Sekurova, Olga N. Pérez-Victoria, Ignacio Martín, Jesús Degnes, Kristin F. Sletta, Håvard Reyes, Fernando Zotchev, Sergey B. Molecules Article Activation of silent biosynthetic gene clusters in Streptomyces bacteria via overexpression of cluster-specific regulatory genes is a promising strategy for the discovery of novel bioactive secondary metabolites. This approach was used in an attempt to activate a cryptic gene cluster in a marine sponge-derived Streptomyces albus PVA94-07 presumably governing the biosynthesis of peptide-based secondary metabolites. While no new peptide-based metabolites were detected in the recombinant strain, it was shown to produce at least four new analogues of deferoxamine with additional acyl and sugar moieties, for which chemical structures were fully elucidated. Biological activity tests of two of the new deferoxamine analogues revealed weak activity against Escherichia coli. The gene knockout experiment in the gene cluster targeted for activation, as well as overexpression of certain genes from this cluster did not have an effect on the production of these compounds by the strain overexpressing the regulator. It seems plausible that the production of such compounds is a response to stress imposed by the production of an as-yet unidentified metabolite specified by the cryptic cluster. MDPI 2016-08-27 /pmc/articles/PMC6273380/ /pubmed/27618884 http://dx.doi.org/10.3390/molecules21091131 Text en © 2016 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sekurova, Olga N.
Pérez-Victoria, Ignacio
Martín, Jesús
Degnes, Kristin F.
Sletta, Håvard
Reyes, Fernando
Zotchev, Sergey B.
New Deferoxamine Glycoconjugates Produced upon Overexpression of Pathway-Specific Regulatory Gene in the Marine Sponge-Derived Streptomyces albus PVA94-07
title New Deferoxamine Glycoconjugates Produced upon Overexpression of Pathway-Specific Regulatory Gene in the Marine Sponge-Derived Streptomyces albus PVA94-07
title_full New Deferoxamine Glycoconjugates Produced upon Overexpression of Pathway-Specific Regulatory Gene in the Marine Sponge-Derived Streptomyces albus PVA94-07
title_fullStr New Deferoxamine Glycoconjugates Produced upon Overexpression of Pathway-Specific Regulatory Gene in the Marine Sponge-Derived Streptomyces albus PVA94-07
title_full_unstemmed New Deferoxamine Glycoconjugates Produced upon Overexpression of Pathway-Specific Regulatory Gene in the Marine Sponge-Derived Streptomyces albus PVA94-07
title_short New Deferoxamine Glycoconjugates Produced upon Overexpression of Pathway-Specific Regulatory Gene in the Marine Sponge-Derived Streptomyces albus PVA94-07
title_sort new deferoxamine glycoconjugates produced upon overexpression of pathway-specific regulatory gene in the marine sponge-derived streptomyces albus pva94-07
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273380/
https://www.ncbi.nlm.nih.gov/pubmed/27618884
http://dx.doi.org/10.3390/molecules21091131
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