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In vitro dual (anticancer and antiviral) activity of the carotenoids produced by haloalkaliphilic archaeon Natrialba sp. M6.

ABSTRACT: Halophilic archaea are a promising natural source of carotenoids. However, little information is available about the biological impacts of these archaeal metabolites. Here, carotenoids of Natrialba sp. M6, which was isolated from Wadi El-Natrun, were produced, purified and identified by Raman spectroscopy, GC-mass spectrometry, and Fourier transform infrared spectroscopy, LC-mass spectrometry and Nuclear magnetic resonance spectroscopy. The C50 carotenoid bacterioruberin was found to be the predominant compound. Because cancer and viral hepatitis are serious diseases, the anticancer, anti-HCV and anti-HBV potentials of these extracted carotenoids (pigments) were examined for the first time. In vitro results indicated that the caspase-mediated apoptotic anticancer effect of this pigment and its inhibitory efficacy against matrix metalloprotease 9 were significantly higher than those of 5-fluorouracil. Furthermore, the extracted pigment exhibited significantly stronger activity for eliminating HCV and HBV in infected human blood mononuclear cells than currently used drugs. This antiviral activity may be attributed to its inhibitory potential against HCV RNA and HBV DNA polymerases, which thereby suppresses HCV and HBV replication, as indicated by a high viral clearance % in the treated cells. These novel findings suggest that the C50 carotenoid of Natrialba sp. M6 can be used as an alternative source of natural metabolites that confer potent anticancer and antiviral activities.

SUBMITTER: Hegazy GE

PROVIDER: S-EPMC7136267 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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In vitro dual (anticancer and antiviral) activity of the carotenoids produced by haloalkaliphilic archaeon Natrialba sp. M6.

Hegazy Ghada E GE Abu-Serie Marwa M MM Abo-Elela Gehan M GM Ghozlan Hanan H Sabry Soraya A SA Soliman Nadia A NA Abdel-Fattah Yasser R YR

Scientific reports 20200406 1

Halophilic archaea are a promising natural source of carotenoids. However, little information is available about the biological impacts of these archaeal metabolites. Here, carotenoids of Natrialba sp. M6, which was isolated from Wadi El-Natrun, were produced, purified and identified by Raman spectroscopy, GC-mass spectrometry, and Fourier transform infrared spectroscopy, LC-mass spectrometry and Nuclear magnetic resonance spectroscopy. The C<sub>50</sub> carotenoid bacterioruberin was found to ...[more]

PMID: 32249805

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Project description:Halophilic archaea is considered an promising natural source of many important metabolites. This study focused on one of the surface-active biomolecules named biosurfactants produced by haloarchaeon Natrialba sp. M6. The production trend was optimized and the product was partially purified and identified using GC-Mass spectrometry. Sequential optimization approaches, Plackett-Burman (PB) and Box-Behnken Designs (BBD) were applied to maximize the biosurfactants production from M6 strain by using 14 factors; pH, NaCl, agitation and glycerol; the most significant factors that influenced the biosurfactant production were used for Response Surface Methodology (RSM). The final optimal production conditions were agitation (150 rpm), glycerol (3%), NaCl (20.8%), pH (12) and cultivation temperature (37°C). GC-Mass spectrometry for the recovered extract revealed the presence of a diverse group of bipolar nature, hydrophobic hydrocarbon chain and charged function group. The majority of these compounds are fatty acids. Based on results of GC-MS, compositional analysis content and Zetasizer, it was proposed that the extracted biosurfactant produced by haloarchaeon Natrialba sp. M6 could be a cationic lipoprotein. The antiviral activity of such biosurfactant was investigated against hepatitis C (HCV) and herpes simplex (HSV1) viruses at its maximum safe doses (20 μg/mL and 8 μg/mL, respectively). Its mode of antiviral action was declared to be primarily via deactivating viral envelopes thus preventing viral entry. Moreover, this biosurfactant inhibited RNA polymerase- and DNA polymerase-mediated viral replication at IC50 of 2.28 and 4.39 μg/mL, respectively also. Molecular docking studies showed that surfactin resided well and was bound to the specified motif with low and accepted binding energies (ΔG = - 5.629, - 6.997 kcal/mol) respectively. Therefore, such biosurfactant could be presented as a natural safe and effective novel antiviral agent.

Project description:BackgroundThe genus Planococcus is comprised of halophilic bacteria generally reported for the production of carotenoid pigments and biosurfactants. In previous work, we showed that the culturing of the orange-pigmented Planococcus sp. CP5-4 isolate increased the evaporation rate of industrial wastewater brine effluent, which we attributed to the orange pigment. This demonstrated the potential application of this bacterium for industrial brine effluent management in evaporation ponds for inland desalination plants. Here we identified a C30-carotenoid biosynthetic gene cluster responsible for pigment biosynthesis in Planococcus sp. CP5-4 through isolation of mutants and genome sequencing. We further compare the core genes of the carotenoid biosynthetic gene clusters identified from different Planococcus species' genomes which grouped into gene cluster families containing BGCs linked to different carotenoid product chemotypes. Lastly, LC-MS analysis of saponified and unsaponified pigment extracts obtained from cultures of Planococcus sp. CP5-4, revealed the structure of the main (predominant) glucosylated C30-carotenoid fatty acid ester produced by Planococcus sp. CP5-4.ResultsGenome sequence comparisons of isolated mutant strains of Planococcus sp. CP5-4 showed deletions of 146 Kb and 3 Kb for the non-pigmented and "yellow" mutants respectively. Eight candidate genes, likely responsible for C30-carotenoid biosynthesis, were identified on the wild-type genome region corresponding to the deleted segment in the non-pigmented mutant. Six of the eight candidate genes formed a biosynthetic gene cluster. A truncation of crtP was responsible for the "yellow" mutant phenotype. Genome annotation revealed that the genes encoded 4,4'-diapolycopene oxygenase (CrtNb), 4,4'- diapolycopen-4-al dehydrogenase (CrtNc), 4,4'-diapophytoene desaturase (CrtN), 4,4'- diaponeurosporene oxygenase (CrtP), glycerol acyltransferase (Agpat), family 2 glucosyl transferase 2 (Gtf2), phytoene/squalene synthase (CrtM), and cytochrome P450 hydroxylase enzymes. Carotenoid analysis showed that a glucosylated C30-carotenoid fatty acid ester, methyl 5-(6-C17:3)-glucosyl-5, 6'-dihydro-apo-4, 4'-lycopenoate was the main carotenoid compound produced by Planococcus sp. CP5-4.ConclusionWe identified and characterized the carotenoid biosynthetic gene cluster and the C30-carotenoid compound produced by Planococcus sp. CP5-4. Mass-spectrometry guided analysis of the saponified and unsaponified pigment extracts showed that methyl 5-glucosyl-5, 6-dihydro-apo-4, 4'-lycopenoate esterified to heptadecatrienoic acid (C17:3). Furthermore, through phylogenetic analysis of the core carotenoid BGCs of Planococcus species we show that various C30-carotenoid product chemotypes, apart from methyl 5-glucosyl-5, 6-dihydro-apo-4, 4'-lycopenoate and 5-glucosyl-4, 4-diaponeurosporen-4'-ol-4-oic acid, may be produced that could offer opportunities for a variety of applications.

Dataset Information

In vitro dual (anticancer and antiviral) activity of the carotenoids produced by haloalkaliphilic archaeon Natrialba sp. M6.

Publications

In vitro dual (anticancer and antiviral) activity of the carotenoids produced by haloalkaliphilic archaeon Natrialba sp. M6.

Similar Datasets

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