Master Degree / Yüksek Lisans Tezleri

Permanent URI for this collectionhttps://hdl.handle.net/11147/3008

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  • Master Thesis
    Induction of Secondary Metabolism of Some Marine Derived Streptomyces Species, and Isolation and Identification of Their Bioactive Secondary Metabolites
    (Izmir Institute of Technology, 2020) Gezer, Emre; Büyükkileci, Ali Oğuz; Bedir, Erdal; Gezer, Emre; Bedir, Erdal; Büyükkileci, Ali Oğuz; 03.01. Department of Bioengineering; 01. Izmir Institute of Technology; 03.08. Department of Food Engineering; 03. Faculty of Engineering
    Secondary metabolites are natural products with low molecular weight produced by different organisms. These metabolites have a wide variety of bioactivities because of their adaptive roles in the nature. These properties make secondary metabolites important source in drug discovery studies. Streptomyces genus, on the other hand, attracts attention due to their ability to produce many secondary metabolites for the treatment of various diseases, especially infectious diseases and cancer. However, secondary metabolism is not fully expressed under standard laboratory conditions as in nature. This phenomenon limits the discovery of new/novel bioactive molecules from the microbial sources. In this study, a previously studied marine derived actinobacterium, namely Streptomyces cacaoi, was investigated further to discover new antimicrobial metabolites via medium and temperature optimization using Box Behnken design. As a result, GPM medium containing 2.25% glycerol, 1% peptone water, 0.2% CaCO3, 0.1% MgCl2 in distilled water was found to provide the highest chemical diversity with potent bioactivity at 30oC. In subsequent studies, inductive effects of some microorganisms and inorganic compounds on secondary metabolism were also determined. Using optimized conditions, a larger fermentation study was undertaken (25 L) followed by extraction and isolation procedures. Sixteen metabolites were purified by chromatographic methods, and structures of the isolates were elucidated by spectral methods. Thirteen compounds, five of which were new, were members of polyketide-type polyether antibiotics. The structures of other molecules were determined as cyclo(Thr-Trp), 6-hydroxy-6-methyloctanoic acid, and 5-hydroxy-1,6-diazacycloundec-5-en-2-one, and all were found to be new. In antimicrobial tests, most polyethers were found to be active against Gram-positive bacteria. In particular, two new polyethers SC-EG-05 and SC-EG-07 showed higher antimicrobial activity than widely used antibiotic vancomycin
  • Master Thesis
    Effects of Polyether Antibiotics on Autophagy
    (Izmir Institute of Technology, 2017) Tosun, Çiğdem; Tosun, Çiğdem; Bedir, Erdal; Tosun, Çiğdem; Bedir, Erdal; 04.03. Department of Molecular Biology and Genetics; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 04. Faculty of Science; 01. Izmir Institute of Technology
    Treatment of cancer is one of the crucial enigma for scientific world and that’s why much effort needs to be put in place for the resolution of this challenge in alternative ways. Autophagy is believed to have an important role in tumor development and progression. The natural polyether antibiotics might be important chemotherapeutic agents to cure cancer by modulating autophagy. The primary goal of this study was to investigate the cytotoxic effects and autophagic mechanism of actions of three polyether antibiotics, one of which was a new secondary metabolite isolated from the marine Streptomyces cacaoi. The effects of these polyether antibiotics were investigated along with previously known autophagy modulators from the same group (Monensin). To achieve this goal, cytotoxicities of these polyether type compounds on three different type of cancer cell lines along with two healthy cell lines were investigated followed by a search to reveal the effects of these compounds on autophagy in cancer cell lines. Methodology of this study consists of mammalian cell culturing, cytotoxicity screening, staining and quantification of acidic compartments inside the cells and studying different autophagy markers along with other associated proteins under various conditions by using Western blotting. This study revealed that the tested polyether antibiotics were autophagy inhibitors as well as inducers of apoptosis in cervical, colorectal and prostate cancer cells. The obtained results will be of significance for the field of anticancer drugdevelopment; however, before one places these secondary metabolites as potential drug candidates, further studies including in vivo experiments are warranted.