Cytotoxic and apoptotic evaluations of marine bacteria isolated from brine-seawater interface of the Red Sea.

BACKGROUND: High salinity and temperature combined with presence of heavy metals and low oxygen renders deep-sea anoxic brines of the Red Sea as one of the most extreme environments on Earth. The ability to adapt and survive in these extreme environments makes inhabiting bacteria interesting candidates for the search of novel bioactive molecules. METHODS: Total 20 i.e. lipophilic (chloroform) and hydrophilic (70% ethanol) extracts of marine bacteria isolated from brine-seawater interface of the Red Sea were tested for cytotoxic and apoptotic activity against three human cancer cell lines, i.e. HeLa (cervical carcinoma), MCF-7 (Breast Adenocarcinoma) and DU145 (Prostate carcinoma). RESULTS: Among these, twelve extracts were found to be very active after 24 hours of treatment, which were further evaluated for their cytotoxic and apoptotic effects at 48 hr. The extracts from the isolates P1-37B and P3-37A (Halomonas) and P1-17B (Sulfitobacter) have been found to be the most potent against tested cancer cell lines. CONCLUSION: Overall, bacterial isolates from the Red Sea displayed promising results and can be explored further to find novel drug-like molecules. The cell line specific activity of the extracts may be attributed to the presence of different polarity compounds or the cancer type i.e. biological differences in cell lines and different mechanisms of action of programmed cell death prevalent in different cancer cell lines

The Kolumbo submarine volcano of Santorini island is a large pool of bacterial strains with antimicrobial activity

Microbes in hydrothermal vents with their unique secondary metabolism may represent an untapped potential source of new natural products. In this study, samples were collected from the hydrothermal field of Kolumbo submarine volcano in the Aegean Sea, in order to isolate bacteria with antimicrobial activity. Eight hundred and thirty-two aerobic heterotrophic bacteria were isolated and then differentiated through BOX-PCR analysis at the strain level into 230 genomic fingerprints, which were screened against 13 different type strains (pathogenic and nonpathogenic) of Gram-positive, Gram-negative bacteria and fungi. Forty-two out of 176 bioactive-producing genotypes (76 %) exhibited antimicrobial activity against at least four different type strains and were selected for 16S rDNA sequencing and screening for nonribosomal peptide (NRPS) and polyketide (PKS) synthases genes. The isolates were assigned to genus Bacillus and Proteobacteria, and 20 strains harbored either NRPS, PKS type I or both genes. This is the first report on the diversity of culturable mesophilic bacteria associated with antimicrobial activity from Kolumbo area; the extremely high proportion of antimicrobial-producing strains suggested that this unique environment may represent a potential reservoir of novel bioactive compounds

Trends in the Discovery of New Marine Natural Products from Invertebrates over the Last Two Decades – Where and What Are We Bioprospecting?

It is acknowledged that marine invertebrates produce bioactive natural products that may be useful for developing new drugs. By exploring untapped geographical sources and/or novel groups of organisms one can maximize the search for new marine drugs to treat human diseases. The goal of this paper is to analyse the trends associated with the discovery of new marine natural products from invertebrates (NMNPI) over the last two decades. The analysis considers different taxonomical levels and geographical approaches of bioprospected species. Additionally, this research is also directed to provide new insights into less bioprospected taxa and world regions. In order to gather the information available on NMNPI, the yearly-published reviews of Marine Natural Products covering 1990–2009 were surveyed. Information on source organisms, specifically taxonomical information and collection sites, was assembled together with additional geographical information collected from the articles originally describing the new natural product. Almost 10000 NMNPI were discovered since 1990, with a pronounced increase between decades. Porifera and Cnidaria were the two dominant sources of NMNPI worldwide. The exception was polar regions where Echinodermata dominated. The majority of species that yielded the new natural products belong to only one class of each Porifera and Cnidaria phyla (Demospongiae and Anthozoa, respectively). Increased bioprospecting efforts were observed in the Pacific Ocean, particularly in Asian countries that are associated with the Japan Biodiversity Hotspot and the Kuroshio Current. Although results show comparably less NMNPI from polar regions, the number of new natural products per species is similar to that recorded for other regions. The present study provides information to future bioprospecting efforts addressing previously unexplored taxonomic groups and/or regions. We also highlight how marine invertebrates, which in some cases have no commercial value, may become highly valuable in the ongoing search for new drugs from the sea

Evolutional and clinical implications of the epigenetic regulation of protein glycosylation

Protein N glycosylation is an ancient posttranslational modification that enriches protein structure and function. The addition of one or more complex oligosaccharides (glycans) to the backbones of the majority of eukaryotic proteins makes the glycoproteome several orders of magnitude more complex than the proteome itself. Contrary to polypeptides, which are defined by a sequence of nucleotides in the corresponding genes, glycan parts of glycoproteins are synthesized by the activity of hundreds of factors forming a complex dynamic network. These are defined by both the DNA sequence and the modes of regulating gene expression levels of all the genes involved in N glycosylation. Due to the absence of a direct genetic template, glycans are particularly versatile and apparently a large part of human variation derives from differences in protein glycosylation. However, composition of the individual glycome is temporally very constant, indicating the existence of stable regulatory mechanisms. Studies of epigenetic mechanisms involved in protein glycosylation are still scarce, but the results suggest that they might not only be important for the maintenance of a particular glycophenotype through cell division and potentially across generations but also for the introduction of changes during the adaptive evolution

Genomics Meets Glycomics—The First GWAS Study of Human N-Glycome Identifies HNF1α as a Master Regulator of Plasma Protein Fucosylation

Over half of all proteins are glycosylated, and alterations in glycosylation have been observed in numerous physiological and pathological processes. Attached glycans significantly affect protein function; but, contrary to polypeptides, they are not directly encoded by genes, and the complex processes that regulate their assembly are poorly understood. A novel approach combining genome-wide association and high-throughput glycomics analysis of 2,705 individuals in three population cohorts showed that common variants in the Hepatocyte Nuclear Factor 1α (HNF1α) and fucosyltransferase genes FUT6 and FUT8 influence N-glycan levels in human plasma. We show that HNF1α and its downstream target HNF4α regulate the expression of key fucosyltransferase and fucose biosynthesis genes. Moreover, we show that HNF1α is both necessary and sufficient to drive the expression of these genes in hepatic cells. These results reveal a new role for HNF1α as a master transcriptional regulator of multiple stages in the fucosylation process. This mechanism has implications for the regulation of immunity, embryonic development, and protein folding, as well as for our understanding of the molecular mechanisms underlying cancer, coronary heart disease, and metabolic and inflammatory disorders

Synthesis of novel sugar diamino acids

Sugar amino acids (SAAs) are found in nature as good construction elements for the preparation of peptide mimetics and oiigosaccharides in drug design and development. The synthesis of SAAs is readily accomplished in few steps and more than 40 SAAs have been synthesised to date.2 Sugar amino acids with an additional amino group, the sugar diamino acid (SDAs) would represent a useful expansion to the library of SAAs available because one of the amino group and carboxylic acid is available for peptide coupling and the another amino/azide group allow to do further derivatisation via peptide or click chemistry such as labelling. However, the synthesis of SDAs is challenging and only three general type have been reported to date.2 As part of a project involving the synthesiso f novel integrin antagonists, we require a new series of SDAs to be developed. Herein, the synthesis of the novel SDAs type 1 and 2 and their applications will be presented. Reference: (1) Gruner, S. A.; Locardi, E.; Lohof, E.; Kessler, H. Chemical Reviews 2002, 102, 491-514. (2) Risseeuw, M. D. P.; Overhand, M.; Fleet,G . W J.; Simone. M. I. Tetrahedron: Asymmetry 2007, 18, 2001-2010

Periphylla sp.

SwimmingJellyfish - from pipe-laying survey, NWS, Australia

Comparison of polar metabolites in Australian deep-sea sponges using HPLC-ESI-HRMS in combination with multivariate analysis

Abstract of paper that presented at 8th Joint Meeting of AFERP, ASP, GA, PSE and SIF, New York City, July 28 - August 1, 2012

Effects of nutrients and processing on the nutritionally important metabolites of Ulva sp. (Chlorophyta)

© 2018 Elsevier B.V. In consideration that, fatty acids bound within phospholipids may exhibit greater levels of bioavailability than neutral lipids, we investigated the effect of nutrient starvation on the phospholipid content and composition of cultivated Ulva biomass. Furthermore, we explored the simultaneous effects on the pigment and phenolic profiles and then correlation analysis to anti-oxidant and anti-inflammatory activity. High nutrient cultivation (nitrogen replete) provided a biomass with desirable n-6/n-3 (0.3) and 18:2n-6/18:3n-3 (0.5) ratios and beneficial 18:4n-3, 20:5n-3, 22:5n-3 fatty acids. These fatty acids dominated the abundant neutral lipid fraction, which comprised 62% of the lipid extract. The remaining phospholipids (38%) were characterised by high 16:0 (49.6%), 18:1n-7 (14.6%) and 18:3n-3 (13.6%) fatty acids. Nutrient-depleted samples had a 3-fold higher total fatty acid (TFA) content (12.05 mg·g−1 d.w, p < 0.0001) compared to nutrient replete samples (3.35 mg·g−1 d.w.). This occurred mostly within the neutral fraction, which represented 88% of the total lipids and the fatty acids 16:0 (4.02 ± 0.15 mg·g−1), 18:1n-7 (1.79 ± 0.06 mg·g−1), 18:2n-6 (2.30 ± 0.08 mg·g−1) and 18:3n-3 (1.09 ± 0.03 mg·g−1 d.w). Nutrient replete biomass yielded 1.5 mg·g−1 total chlorophyll, 0.1 mg·g−1 carotenoids and 1.6 mg·g−1 phenolics, whilst low nutrient growth conditions reduced the presence of pigments by 98%, phenolics by 34% and anti-oxidant activity by 87%. Significantly higher yields of pigment and phenolics were obtained using 95% ethanol for the extraction process, whilst acetone extracts were characterised by a higher proportion of carotenoids. All extracts from cultivated Ulva samples inhibited nitric oxide (NO) (≥81%) with acetone extracts demonstrating higher inhibition (94–97%) than 95% ethanol extracts (81–90%) with no significant effects observed between the two treatments. Thus, Ulva cultivated under high nutrients offers a sustainable source of potential biomass for n-3 PUFA, pigments and phenolics with attributable anti-oxidant and anti-inflammatory activity

Parameters affecting the analytical profile of fatty acids in the macroalgal genus Ulva.

The fatty acids (FA) of Ulva have potential to contribute to nutrition. However the large variability of FA profiles of Ulva species; thus the quality and quantity of FA in relation to nutrition is poorly defined. Herein we investigate the FA profile of 74 cultured Ulva samples crossing five culture regimes, six extraction regimes and four post-harvesting processes. This is compared alongside a comprehensive review of FA profiles of Ulva spp. With regard to the literature, Ulva is characterised by C16:0 (30.5±11.5%), C18:3 n-3 (14.5±6.3%), C18:4 n-3 (12.5±5.4%), C16:4 n-3 (8.9±4.8%) and C18:1 n-7 (10.1±4.0%). The investigated Ulva fell within the reported range of specific FA. High nutrient conditions showed the most desirable FA profile for health, along with the highest total FA content (56mgg(-1) dry weight equivalent) when extracted with an optimised protocol