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New Metabolites and Bioactive Actinomycins from Marine-Derived Streptomyces sp. ZZ338.

ABSTRACT: An extract prepared from the culture of a marine-derived actinomycete Streptomyces sp. ZZ338 was found to have significant antimicrobial and antiproliferative activities. A chemical investigation of this active extract resulted in the isolation of three known bioactive actinomycins (1-3) and two new metabolites (4 and 5). The structures of the isolated compounds were identified as actinomycins D (1), V (2), X_0? (3), 2-acetylamino-3-hydroxyl-4-methyl-benzoic acid methyl ester (4), and N-1S-(4-methylaminophenylmethyl)-2-oxo-propyl acetamide (5) based on their nuclear magnetic resonance (NMR) and high resolution electrospray ionization mass spectroscopy (HRESIMS) data as well as their optical rotation. This class of new compound 5 had never before been found from a natural resource. Three known actinomycins showed activities in inhibiting the proliferation of glioma cells and the growth of methicillin-resistant Staphylococcus aureus, Escherichia coli, and Candida albicans and are responsible for the activity of the crude extract. Actinomycin D (1) was also found to downregulate several glioma metabolic enzymes of glycolysis, glutaminolysis, and lipogenesis, suggesting that targeting multiple tumor metabolic regulators might be a new anti-glioma mechanism of actinomycin D. This is the first report of such a possible mechanism for the class of actinomycins.

SUBMITTER: Zhang X

PROVIDER: S-EPMC5082329 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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New Metabolites and Bioactive Actinomycins from Marine-Derived Streptomyces sp. ZZ338.

Zhang Xiufang X Ye Xuewei X Chai Weiyun W Lian Xiao-Yuan XY Zhang Zhizhen Z

Marine drugs 20161011 10

An extract prepared from the culture of a marine-derived actinomycete Streptomyces sp. ZZ338 was found to have significant antimicrobial and antiproliferative activities. A chemical investigation of this active extract resulted in the isolation of three known bioactive actinomycins (1-3) and two new metabolites (4 and 5). The structures of the isolated compounds were identified as actinomycins D (1), V (2), X0β (3), 2-acetylamino ...[more]

PMID: 27727167

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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.

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New Metabolites and Bioactive Actinomycins from Marine-Derived Streptomyces sp. ZZ338.

Publications

New Metabolites and Bioactive Actinomycins from Marine-Derived Streptomyces sp. ZZ338.

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