Bioengineering / Biyomühendislik
Permanent URI for this collectionhttps://hdl.handle.net/11147/4529
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Conference Object Citation - WoS: 1The Effects of Novel Telomerase Activators on Human Adipose-Derived Mesenchymal Stem Cell (had-Msc) Proliferation and Osteogenic Differentiation(Georg Thieme Verlag Kg, 2022) Kuru, G.; Küçüksolak, Melis; Pulat, G.; Karaman, O.; Bedir, Erdal[No Abstract Available]Conference Object Citation - WoS: 1Secondary Metabolites From Endophytic Fungus Penicilium Roseopurpureum and Investigation of Their Cytotoxic Activities(Georg Thieme Verlag, 2022) Dizmen, Berivan; Üner, Göklem; Küçüksolak, Melis; Ballar Kırmızıbayrak, Petek; Bedir, Erdal[No Abstract Available]Conference Object Short Lecture Novel Neuroprotective Metabolites Produced Via Biotransformation of Cyclocephagenol by Alternaria Eureka 1e1bl1(Georg Thieme Verlag, 2022) Küçüksolak, Melis; Üner, Göklem; Ballar Kırmızıbayrak, Petek; Bedir, ErdalNeurodegeneration refers to the loss of structure/function of neurons leading to neurological diseases including Alzheimerʼs and Parkinsonʼs. The discovery of novel therapeutics against neurodegenerative diseases has been an area of intense research as neurodegenerative diseases are a huge burden on society and the economy [1]. Numerous studies reported that natural products have the potential to prevent and treat neurodegeneration. Among these studies, the neuroprotective activities of cycloartane-type saponins are noteworthy [2], [3]. In our preliminary studies, the neuroprotective activity of cyclocephagenol, an aglycone of cyclocephaloside I from Astragalus microcephalus [4], was screened for H2O2-induced injury in SH-SY5Y cells. Based on the promising bioactivity of cyclocephagenol, the aims of this study were: i) to perform microbial transformation studies on cyclocephagenol using Alternaria eureka followed by isolation and structural characterization of the metabolites; ii) to investigate neuroprotective activities of the metabolites; iii) to understand structure-activity relationships towards neuroprotection.Conference Object A New Iminol Derivative From Streptomyces Cacaoi in New Fermentation Conditions(Georg Thieme Verlag, 2022) Gezer, Emre; Küçüksolak, Melis; Bilgi, Eyüp; Bedir, ErdalMarine-derived organisms have varied secondary metabolism due to their adaptation to extreme conditions of marine environments. This fact has made marine-derived Actinobacteria promising sources of new/novel compounds. In addition, the expression of secondary metabolite gene clusters is typically under the control of environmental conditions that cause many of the biosynthetic gene clusters to be silent under laboratory conditions. Thus, the determination of proper fermentation conditions becomes crucial for discovering new molecules.Article Citation - WoS: 5Citation - Scopus: 6Undescribed Polyether Ionophores From Streptomyces Cacaoi and Their Antibacterial and Antiproliferative Activities(Elsevier, 2022) Gezer, Emre; Üner, Göklem; Küçüksolak, Melis; Kurt, Mustafa Ünver; Doğan, Gamze; Ballar Kırmızıbayrak, Petek; Bedir, ErdalPolyether ionophores represent a large group of naturally occurring compounds mainly produced by Streptomyces species. With previously proven varieties of bioactivity including antibacterial, antifungal, antiparasitic, antiviral and anti-tumor effects, the discovery of undescribed polyethers leading to development of efficient therapeutics has become important. As part of our research on polyether-rich Streptomyces cacaoi, we previously performed modification studies on fermentation conditions to induce synthesis of specialized metabolites. Here, we report four undescribed and nine known polyether compounds from S. cacaoi grown in optimized conditions. Antimicrobial activity assays revealed that four compounds, including the undescribed (6), showed strong inhibitory effects over both Bacillus subtilis and methicillin-resistant Staphylococcus aureus (MRSA) growth. Additionally, K41-A and its C15-demethoxy derivative exhibited significant cytotoxicity. These results signified that selectivity of C15-demethoxy K41-A towards cancer cells was higher than K41-A, which prompted us to conduct mechanistic experiments. These studies showed that this uninvestigated compound acts as a multitarget compound by inhibiting autophagic flux, inducing reactive oxygen species formation, abolishing proteasome activity, and stimulating ER stress. Consequently, the optimized fermentation conditions of S. cacaoi led to the isolation of undescribed and known polyethers displaying promising activities.Article Citation - WoS: 12Citation - Scopus: 12New Cardenolides From Biotransformation of Gitoxigenin by the Endophytic Fungus Alternaria Eureka 1e1bl1: Characterization and Cytotoxic Activities(MDPI, 2021) Bedir, Erdal; Karakoyun, Çiğdem; Doğan, Gamze; Kuru, Gülten; Küçüksolak, Melis; Yusufoğlu, HasanMicrobial biotransformation is an important tool in drug discovery and for metabolism studies. To expand our bioactive natural product library via modification and to identify possible mammalian metabolites, a cytotoxic cardenolide (gitoxigenin) was biotransformed using the endophytic fungus Alternaria eureka 1E1BL1. Initially, oleandrin was isolated from the dried leaves of Nerium oleander L. and subjected to an acid-catalysed hydrolysis to obtain the substrate gitoxigenin (yield; similar to 25%). After 21 days of incubation, five new cardenolides 1, 3, 4, 6, and 8 and three previously- identified compounds 2, 5 and 7 were isolated using chromatographic methods. Structural elucidations were accomplished through 1D/2D NMR, HR-ESI-MS and FT-IR analysis. A. eureka catalyzed oxygenation, oxidation, epimerization and dimethyl acetal formation reactions on the substrate. Cytotoxicity of the metabolites were evaluated using MTT cell viability method, whereas doxorubicin and oleandrin were used as positive controls. Biotransformation products displayed less cytotoxicity than the substrate. The new metabolite 8 exhibited the highest activity with IC50 values of 8.25, 1.95 and 3.4 mu M against A549, PANC-1 and MIA PaCa-2 cells, respectively, without causing toxicity on healthy cell lines (MRC-5 and HEK-293) up to concentration of 10 mu M. Our results suggest that A. eureka is an effective biocatalyst for modifying cardenolide-type secondary metabolites.Conference Object Induction of Secondary Metabolism of Marine Derived Streptomyces Cacaoi(Georg Thieme Verlag, 2019) Gezer, Erkin; Bilgi, Eyüp; Küçüksolak, Melis; Bedir, ErdalMicrobial natural products have an adaptive role as signal molecules or defense tools in ecological interactions. Biosynthesis of these molecules is suppressed in standard laboratory conditions where there are no ecological triggers. Thus, only a portion of the chemical diversity of a microbial strain is discovered by standard fermentation protocols. However, using different fermentation conditions or different approaches such as co-culture, biosynthesis of these suppressed molecules can be triggered, and new natural products can be isolated.Conference Object Citation - WoS: 1Telomerase Activators Derived From Astragalus Sapogenins Via Biotransformation With the Recently Discovered Endophytic Fungus Camarosporium Laburnicola(Georg Thieme Verlag, 2019) Küçüksolak, Melis; Ekiz, Güner; Duman, Seda; Yılmaz, Sinem; Ballar Kırmızıbayrak, Petek; Bedir, ErdalTelomeres are nucleotide sequences that are located at the end of chromosomes shortening with each cell division. Telomerase is a reverse transcriptase enzyme, and it helps to replenish telomere ends that are truncated by aging and stress factors.