Bioengineering / Biyomühendislik
Permanent URI for this collectionhttps://hdl.handle.net/11147/4529
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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.