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      Evaluation of Antioxidative and Cytotoxic Activities of Streptomyces pluripotens MUSC 137 Isolated from Mangrove Soil in Malaysia

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          Abstract

          Streptomyces pluripotens MUSC 137 was isolated from mangrove soil obtained from Tanjung Lumpur, Pahang, Malaysia. We investigated the phylogenetic, genomic, biochemical, and phenotypic characteristics of this strain. Uniquely adapted microorganisms from mangrove habitats have previously yielded compounds of biopharmaceutical interest. In order to examine the bioactivities possessed by the strain, fermentation extract was prepared through solvent extraction method prior to bioactivities screenings. Antioxidant activity was examined via DPPH assay while the cytotoxic effect was assessed by means of examining the activity of the extract against selected human cancer cell lines, namely colon cancer cells (HCT-116, Caco-2, SW480, and HT-29), breast cancer cell (MCF-7), lung cancer cell (A549), prostate cancer cell (DU145), and cervical cancer cell (Ca Ski). The results revealed MUSC 137 possesses significant antioxidant activity and demonstrates cytotoxic effect against several cancer cell lines tested. The results indicated MCF-7 cells were most susceptible to the extract with the lowest IC 50 (61.33 ± 17.10 μg/mL), followed by HCT-116 and A549. Additionally, selective index (SI) showed that MUSC 137 extract was less toxic against normal cell lines when compared to MCF-7 and HCT-116 cells. The extract was further subjected to chemical analysis using GC–MS and revealed the presence of deferoxamine and pyrrolizidines related compounds which may account for the antioxidant and cytotoxic properties observed.

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          Introducing EzTaxon-e: a prokaryotic 16S rRNA gene sequence database with phylotypes that represent uncultured species.

          Despite recent advances in commercially optimized identification systems, bacterial identification remains a challenging task in many routine microbiological laboratories, especially in situations where taxonomically novel isolates are involved. The 16S rRNA gene has been used extensively for this task when coupled with a well-curated database, such as EzTaxon, containing sequences of type strains of prokaryotic species with validly published names. Although the EzTaxon database has been widely used for routine identification of prokaryotic isolates, sequences from uncultured prokaryotes have not been considered. Here, the next generation database, named EzTaxon-e, is formally introduced. This new database covers not only species within the formal nomenclatural system but also phylotypes that may represent species in nature. In addition to an identification function based on Basic Local Alignment Search Tool (blast) searches and pairwise global sequence alignments, a new objective method of assessing the degree of completeness in sequencing is proposed. All sequences that are held in the EzTaxon-e database have been subjected to phylogenetic analysis and this has resulted in a complete hierarchical classification system. It is concluded that the EzTaxon-e database provides a useful taxonomic backbone for the identification of cultured and uncultured prokaryotes and offers a valuable means of communication among microbiologists who routinely encounter taxonomically novel isolates. The database and its analytical functions can be found at http://eztaxon-e.ezbiocloud.net/.
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            Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database.

            The tumor suppressor gene TP53 is frequently mutated in human cancers. More than 75% of all mutations are missense substitutions that have been extensively analyzed in various yeast and human cell assays. The International Agency for Research on Cancer (IARC) TP53 database (www-p53.iarc.fr) compiles all genetic variations that have been reported in TP53. Here, we present recent database developments that include new annotations on the functional properties of mutant proteins, and we perform a systematic analysis of the database to determine the functional properties that contribute to the occurrence of mutational "hotspots" in different cancer types and to the phenotype of tumors. This analysis showed that loss of transactivation capacity is a key factor for the selection of missense mutations, and that difference in mutation frequencies is closely related to nucleotide substitution rates along TP53 coding sequence. An interesting new finding is that in patients with an inherited missense mutation, the age at onset of tumors was related to the functional severity of the mutation, mutations with total loss of transactivation activity being associated with earlier cancer onset compared to mutations that retain partial transactivation capacity. Furthermore, 80% of the most common mutants show a capacity to exert dominant-negative effect (DNE) over wild-type p53, compared to only 45% of the less frequent mutants studied, suggesting that DNE may play a role in shaping mutation patterns. These results provide new insights into the factors that shape mutation patterns and influence mutation phenotype, which may have clinical interest.
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              How many antibiotics are produced by the genus Streptomyces?

              Streptomyces is the largest antibiotic-producing genus in the microbial world discovered so far. The number of antimicrobial compounds reported from the species of this genus per year increased almost exponentially for about two decades, followed by a steady rise to reach a peak in the 1970s, and with a substantial decline in the late 1980s and 1990s. The cumulative number shows a sigmoid curve that is much flatter than what a logistic equation would predict. We attempted to fit a mathematical model to this curve in order to estimate the number of undiscovered antimicrobials from this genus as well as to predict the trends in the near future. A model assuming that the screening efforts are encouraged by a previous year's success and that the probability of finding a new antibiotic is a function of the fraction of antibiotics undiscovered so far offered a good fit after optimizing parameters. The model estimated the total number of antimicrobial compounds that this genus is capable of producing to be of the order of a 100,000 - a tiny fraction of which has been unearthed so far. The decline in the slope appeared to be due to a decline in screening efforts rather than an exhaustion of compounds. Left to itself, the slope will become zero in the next one or two decades, but if the screening efforts are maintained constant, the rate of discovery of new compounds will not decline for several decades to come.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                16 December 2015
                2015
                : 6
                : 1398
                Affiliations
                [1] 1Biomedical Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia Bandar Sunway, Malaysia
                [2] 2UKM Medical Molecular Biology Institute–UKM Medical Centre, Universiti Kebangsaan Malaysia Kuala Lumpur, Malaysia
                [3] 3Division of Genetics and Molecular Biology, Institute of Biological Sciences, Faculty of Science, University of Malaya Kuala Lumpur, Malaysia
                Author notes

                Edited by: Dongsheng Zhou, Beijing Institute of Microbiology and Epidemiology, China

                Reviewed by: Jyl Matson, University of Toledo, USA; Lorenzo Giacani, University of Washington, USA

                This article was submitted to Microbial Physiology and Metabolism, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2015.01398
                4679926
                26733951
                2ec0bd57-c054-418d-a85c-2bb752c3d192
                Copyright © 2015 Ser, Ab Mutalib, Yin, Chan, Goh and Lee.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 06 October 2015
                : 24 November 2015
                Page count
                Figures: 4, Tables: 4, Equations: 2, References: 83, Pages: 11, Words: 0
                Categories
                Microbiology
                Original Research

                Microbiology & Virology
                streptomyces pluripotens,cytotoxic,antioxidative,mangrove,actinobacteria
                Microbiology & Virology
                streptomyces pluripotens, cytotoxic, antioxidative, mangrove, actinobacteria

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