Dataset Information

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

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.

SUBMITTER: Sekurova ON

PROVIDER: S-EPMC6273380 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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

Sekurova Olga N ON Pérez-Victoria Ignacio I Martín Jesús J Degnes Kristin F KF Sletta Håvard H Reyes Fernando F Zotchev Sergey B SB

Molecules (Basel, Switzerland) 20160827 9

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 ...[more]

PMID: 27618884

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Project description:Staphylococcus epidermidis, the common inhabitant of human skin and mucosal surfaces has emerged as an important pathogen in patients receiving surgical implants and medical devices. Entering the body via surgical sites and colonizing the medical devices through formation of multi-layered biofilms it leads to refractory and persistent device-related infections (DRIs). Staphylococcal proportions within biofilms are more tolerant to antibiotics and immune responses, and thus are hard-to-treat. The consequent morbidity and mortality, and economic losses in health care systems has strongly necessitated the need for development of new anti-bacterial and anti-biofilm based therapeutics. In this study, we describe the biological activity of a marine sponge-derived Streptomyces sp. SBT348 extract in restraining staphylococcal growth and biofilm formation on polystyrene, glass, medically relevant titan metal and silicone surfaces. A bio-assay guided fractionation was performed to isolate the active compound (C3) from the crude SBT348 extract. Our results demonstrated that C3 effectively inhibits the growth (MIC: 31.25 µg/ml) and biofilm formation (sub-MIC range: 1.95-<31.25 µg/ml) of S. epidermidis RP62A in vitro. Chemical characterization of C3 by heat and enzyme treatments, and High-Resolution Fourier Transform Mass Spectrometry (HRMS) revealed its heat-stable and non-proteinaceous nature, and high molecular weight (1258. 3257 Da). Cytotoxicity profiling of C3 in vitro on mouse fibroblast (NIH/3T3) and macrophage (J774.1) cell lines, and in vivo on the greater wax moth larvae Galleria melonella revealed its non-toxic nature at the effective dose. Transcriptome analysis of C3 treated-S. epidermidis RP62A has further unmasked the negative effect of C3 on central metabolism (carbon, amino acid and protein, lipids, nucleotide and energy) suggesting its mode of action. Taken together, these findings suggest that C3 could be possibly used as antibacterial and antibiofilm coatings on medically-relevant surfaces and prevent the relapsing staphylococcal DRIs.

Dataset Information

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

Publications

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

Similar Datasets

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