Titel
New Deferoxamine Glycoconjugates Produced upon Overexpression of Pathway-Specific Regulatory Gene in the Marine Sponge-Derived Streptomyces albus PVA94-07
Autor*in
Ignacio Pérez-Victoria
Fundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía
Autor*in
Jesús Martín
Fundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía
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Abstract
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.
Stichwort
Streptomycessecondary metabolite biosynthesisgene clusterregulatory genedeferoxamineglycoconjugates
Objekt-Typ
Sprache
Englisch [eng]
Persistent identifier
https://phaidra.univie.ac.at/o:533944
Erschienen in
Titel
Molecules
Band
21
Ausgabe
9
Verlag
MDPI AG
Erscheinungsdatum
2016
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