Please use this identifier to cite or link to this item: https://hdl.handle.net/11147/11913
Title: Undescribed polyether ionophores from Streptomyces cacaoi and their antibacterial and antiproliferative activities
Authors: Gezer, Emre
Üner, Göklem
Küçüksolak, Melis
Kurt, Mustafa Ünver
Doğan, Gamze
Ballar Kırmızıbayrak, Petek
Bedir, Erdal
Izmir Institute of Technology
Izmir Institute of Technology
Izmir Institute of Technology
Izmir Institute of Technology
Izmir Institute of Technology
Ege Üniversitesi
Izmir Institute of Technology
Keywords: Actinobacteria
Autophagy
Polyether ionophores
Streptomyces cacaoi
Streptomycetaceae
Issue Date: Mar-2022
Publisher: Elsevier
Abstract: Polyether 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.
URI: https://doi.org/10.1016/j.phytochem.2021.113038
https://hdl.handle.net/11147/11913
Appears in Collections:Bioengineering / Biyomühendislik
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection

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