Undescribed polyether ionophores from Streptomyces cacaoi and their antibacterial and antiproliferative activities

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dc.authoridKirmizibayrak, Petek Ballar/0000-0002-6189-1818
dc.authoridKUCUKSOLAK, MELIS/0000-0003-1619-4850
dc.authoriduner, Goklem/0000-0003-4970-4837
dc.authoridBedir, Erdal/0000-0003-1262-063X
dc.authoridGezer, Emre/0000-0001-9721-7297
dc.authorscopusid57369524400
dc.authorscopusid57219944322
dc.authorscopusid57205744287
dc.authorscopusid57370075500
dc.authorscopusid57221086660
dc.authorscopusid57222366085
dc.authorscopusid7003998497
dc.authorwosidKirmizibayrak, Petek Ballar/Y-6869-2018
dc.contributor.authorGezer, Emre
dc.contributor.authorUner, Goklem
dc.contributor.authorKucuksolak, Melis
dc.contributor.authorKurt, Mustafa Unver
dc.contributor.authorDogan, Gamze
dc.contributor.authorKirmizibayrak, Petek Ballar
dc.contributor.authorBedir, Erdal
dc.date.accessioned2023-01-12T19:56:09Z
dc.date.available2023-01-12T19:56:09Z
dc.date.issued2022
dc.departmentN/A/Departmenten_US
dc.description.abstractPolyether 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.en_US
dc.description.sponsorshipScientific Research Projects Coordination Unit of Izmir Institute of Technology (IZTECH BAP) [2019IYTE0273]en_US
dc.description.sponsorshipWe are very grateful to the Pharmaceutical Sciences Research Centre (FABAL, Ege University, Faculty of Pharmacy) and Biotechnology and Bioengineering Application Research Centre (BIYOMER, Izmir Institute of Technology) for equipment support. This work was supported by the Scientific Research Projects Coordination Unit of Izmir Institute of Technology (IZTECH BAP) [2019IYTE0273].en_US
dc.identifier.doi10.1016/j.phytochem.2021.113038
dc.identifier.issn0031-9422
dc.identifier.issn1873-3700
dc.identifier.pmid34902703en_US
dc.identifier.scopus2-s2.0-85120932427en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1016/j.phytochem.2021.113038
dc.identifier.urihttps://hdl.handle.net/11454/76811
dc.identifier.volume195en_US
dc.identifier.wosWOS:000761012300008en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherPergamon-Elsevier Science Ltden_US
dc.relation.ispartofPhytochemistryen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectStreptomyces cacaoien_US
dc.subjectStreptomycetaceaeen_US
dc.subjectActinobacteriaen_US
dc.subjectAntibacterialen_US
dc.subjectCytotoxicen_US
dc.subjectPolyether ionophoresen_US
dc.subjectAutophagyen_US
dc.subjectEndoplasmic-Reticulum Stressen_US
dc.subjectUnfolded Protein Responseen_US
dc.subjectAutophagic Fluxen_US
dc.subjectProteasome Inhibitorsen_US
dc.subjectCellsen_US
dc.subjectSalinomycinen_US
dc.subjectApoptosisen_US
dc.subjectNanchangmycinen_US
dc.subjectBiosynthesisen_US
dc.subjectMechanismsen_US
dc.titleUndescribed polyether ionophores from Streptomyces cacaoi and their antibacterial and antiproliferative activitiesen_US
dc.typeArticleen_US

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