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 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.
Department of Pharmacognosy, University of Vienna, 1090 Vienna, Austria. olga.sekurova@univie.ac.at.
Olga N
ON
Sekurova
Fundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, 18016 Armilla, Granada, Spain. ignacio.perez-victoria@medinaandalucia.es.
Ignacio
I
Pérez-Victoria
Fundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, 18016 Armilla, Granada, Spain. jesus.martin@medinaandalucia.es.
Jesús
J
Martín
Department of Biotechnology, SINTEF Materials and Chemistry, N-7465 Trondheim, Norway. Kristin.F.Degnes@sintef.no.
Kristin F
KF
Degnes
Department of Biotechnology, SINTEF Materials and Chemistry, N-7465 Trondheim, Norway. havard.sletta@sintef.no.
Håvard
H
Sletta
Fundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, 18016 Armilla, Granada, Spain. fernando.reyes@medinaandalucia.es.
Fernando
F
Reyes
Department of Pharmacognosy, University of Vienna, 1090 Vienna, Austria. sergey.zotchev@univie.ac.at.
Sergey B
SB
Zotchev
D000818:Animals; D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000494:pharmacology; D059001:Aquatic Organisms / Q000382:microbiology*; D003676:Deferoxamine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004926:Escherichia coli / Q000254:growth & development*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D011161:Porifera / Q000382:microbiology*; D013302:Streptomyces / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D003676:Deferoxamine
Streptomyces; deferoxamine; gene cluster; glycoconjugates; regulatory gene; secondary metabolite biosynthesis