Project description:BACKGROUND:Microbial species in the brine pools of the Red Sea and the brine pool-seawater interfaces are exposed to high temperature, high salinity, low oxygen levels and high concentrations of heavy metals. As adaptations to these harsh conditions require a large suite of secondary metabolites, these microbes have a huge potential as a source of novel anticancer molecules. METHODS:A total of 60 ethyl-acetate extracts of newly isolated strains from extreme environments of the Red-Sea were isolated and tested against several human cancer cell lines for potential cytotoxic and apoptotic activities. RESULTS:Isolates from the Erba brine-pool accounted for 50% of active bacterial extracts capable of inducing 30% or greater inhibition of cell growth. Among the 60 extracts screened, seven showed selectivity towards triple negative BT20 cells compared to normal fibroblasts. CONCLUSION:In this study, we identified several extracts able to induce caspase-dependent apoptosis in various cancer cell lines. Further investigations and isolation of the active compounds of these Red Sea brine pool microbes may offer a chemotherapeutic potential for cancers with limited treatment options.
Project description:Enzymes originating from hostile environments offer exceptional stability under industrial conditions and are therefore highly in demand. Using single-cell genome data, we identified the alcohol dehydrogenase (ADH) gene, adh/a1a, from the Atlantis II Deep Red Sea brine pool. ADH/A1a is highly active at elevated temperatures and high salt concentrations (optima at 70 °C and 4 m KCl) and withstands organic solvents. The polyextremophilic ADH/A1a exhibits a broad substrate scope including aliphatic and aromatic alcohols and is able to reduce cinnamyl-methyl-ketone and raspberry ketone in the reverse reaction, making it a possible candidate for the production of chiral compounds. Here, we report the affiliation of ADH/A1a to a rare enzyme family of microbial cinnamyl alcohol dehydrogenases and explain unique structural features for halo- and thermoadaptation.
Project description:The red sea urchin, Mesocentrotus franciscanus, is one the earth’s longest-lived animals, reported to live more than 100 years with indeterminate growth, life-long reproduction and no increase in mortality rate with age. To explore the idea that transcriptional stability is a key determinant of longevity and negligible senescence, age-related gene expression was examined in three tissues of the red sea urchin (Aristotle’s lantern muscle, esophagus and radial nerve cord). Genome-wide transcriptional profiling using RNA-Seq revealed remarkable stability in muscle and esophagus with very few age-related changes in gene expression. In contrast, expression of more than 900 genes was significantly altered with age in radial nerve cord including genes involved in nerve function, signaling, metabolism, cytoskeleton, transcriptional regulation and chromatin modification. Notably, there was an upregulation in expression of genes involved in synaptogenesis and axonogenesis suggesting enhanced nervous system activity with age. Among the signaling pathways affected by age, there was a downregulation in expression of key components of the mTOR signaling pathway and an upregulation of negative regulators of this pathway. This was accompanied by a reduction in expression of genes involved in protein synthesis and mitochondrial function and an increase in expression of genes that promote autophagy. Downregulation of the mTOR pathway together with the other observed changes reveals a unique age-related gene expression profile in the red sea urchin nervous system that may contribute to mitigation of the detrimental effects of aging in this long-lived animal.