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

Gezer, Emre; Üner, Göklem; Küçüksolak, Melis; Kurt, Mustafa Ünver; Doğan, Gamze; Ballar, Petek; Bedir, Erdal

doi:10.1016/j.phytochem.2021.113038

Cited by 7 publications

(5 citation statements)

References 44 publications

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“…Cacaoidin for example was grown in MPG medium for 13 days (Ortiz-Lopez et al 2020). A series of ionophores from S. cacaoi Waksman and Henrici (Streptomycetaceae) strain JX912350.1 were obtained using an optimized culture medium (Gezer et al 2022). From the response surface methodology, 2.25% glycerol, 1% peptone water, 0.2% CaCO3 and 0.1% MgCl2 in distilled water at 30℃, 150 rpm for 10 days favored the production of four new ionophores belonging to the K41-A class of compounds.…”

Section: Discussionmentioning

confidence: 99%

Genomics and metabolomics-based assessment of the biosynthetic potential of the sponge-associated microorganism Streptomyces cacaoi strain R2A-843A from the Philippines

Malto,

Reyes,

et al. 2023

SciEnggJ

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The biosynthetic machinery of the sponge-associated Streptomyces cacaoi strain R2A-843A was assessed using a combined genomics and metabolomics approach. Whole genome sequencing and molecular networking showed the high biosynthetic potential of this actinomycete. A significant proportion of the genome is dedicated to secondary metabolite production, with biosynthetic gene clusters for nonribosomal peptides, polyketides, and terpenes being the most represented. Seven cyclic pentapeptides, including a putative new analogue, and a glycosylated lanthipeptide were identified using HRMS and untargeted MS/MS analysis. To validate our genome and metabolome analysis, we undertook a mass spectrometry-guided purification and confirmed the production of the known peptides BE18257A (1) and BE-18257B (2). The production of 1 and 2 and the growth of the microorganism were monitored for eight days. Compound 2 was produced at a higher concentration, starting at 48 h post-incubation. Both compounds were noncytotoxic against colorectal and breast cancer cell lines.

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Section: Discussionmentioning

confidence: 99%

Genomics and metabolomics-based assessment of the biosynthetic potential of the sponge-associated microorganism Streptomyces cacaoi strain R2A-843A from the Philippines

Malto,

Reyes,

et al. 2023

SciEnggJ

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“…To detect ROS formation, 2’-7’-Dichlorodihydrofluorescein diacetate (H 2 DCFDA) (Enzo; ALX-610-022-M050) was used as previously reported (Gezer et al, 2022). For this purpose, HEKn cells were pre-treated with indicated concentrations of CA for 1 h. After 1 h pre-treatment of CA, cells were treated with 250 μM H 2 O 2 (hydrogen peroxide) for 24 h. H 2 DCFDA resuspended in 1X PBS at a final concentration of 10 μM was added to the cells and incubated at 37 °C for 30 min (Kapeta et al, 2010).…”

Section: Methodsmentioning

confidence: 99%

The role of Cycloastragenol at the intersection of Nrf-2/ARE, telomerase, and proteasome activity

Yılmaz

Bedir

Ballar

2022

Preprint

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Aging is well-characterized by the gradual decline of cellular functionality. As redox balance, proteostasis, and telomerase systems have been found to be associated with aging and age-related diseases, targeting these systems by small compounds has been considered as a promising therapeutic approach. Cycloastragenol (CA), a small molecule telomerase activator obtained from Astragalus species, has been reported to have positive effects on several age-related pathophysiologies, including ischemia, glucose intolerance, diabetes, and neurodegenerative diseases. Although CA has received intense attention as a promising compound for aging and age-related diseases, the mechanisms underlying CA activity related to redox balance, proteasome, and telomerase has not yet been reported. Here, we presented that CA increased Nrf-2 activity leading to upregulation of cytoprotective enzymes and attenuation of oxidative stress-induced ROS levels. Furthermore, CA enhanced telomerase activity by increasing not only the expression of hTERT but also its nuclear localization via the Hsp90-chaperon complex. CA alleviated the oxidative stress-induced mitochondrial hTERT levels while increasing the nuclear hTERT levels. Additionally, the proteasome activity and assembly were increased by CA. Strikingly, our data revealed that CA-mediated neuroprotection requires both Nrf-2 and hTERT induction. In conclusion, this study is the first report describing the effect of CA on these aging-related three major cellular pathways and their interrelationships. As the proteasome activator effect of CA is dependent on induction of telomerase activity, which is mediated by Nrf-2 system, CA has a great potential for healthier aging and prevention or treatment of age-related diseases by positively affecting these three cellular pathways.

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“…SH-SY5Y cells were seeded onto the 6 well plates and were treated with either compounds or the vesicle for 2 h. Then, cells were treated with 70 µM H 2 O 2 . Following procedures were performed as described previously 34 .…”

Section: Methodsmentioning

confidence: 99%

Neuroprotective metabolites via fungal biotransformation of a novel sapogenin, cyclocephagenol

Küçüksolak

Üner

Ballar

et al. 2022

Sci Rep

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Cyclocephagenol (1), a novel cycloartane-type sapogenin with tetrahydropyran unit, is only encountered in Astragalus species. This rare sapogenin has never been a topic of biological activity or modification studies. The objectives of this study were; (i) to perform microbial transformation studies on cyclocephagenol (1) using Astragalus endophyte, Alternaria eureka 1E1BL1, 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. The microbial transformation of cyclocephagenol (1) using Alternaria eureka resulted in the production of twenty-one (2–22) previously undescribed metabolites. Oxidation, monooxygenation, dehydration, methyl migration, epoxidation, and ring expansion reactions were observed on the triterpenoid skeleton. Structures of the compounds were established by 1D-, 2D-NMR, and HR-MS analyses. The neuroprotective activities of metabolites and parent compound (1) were evaluated against H2O2-induced cell injury. The structure–activity relationship (SAR) was established, and the results revealed that 1 and several other metabolites had potent neuroprotective activity. Further studies revealed that selected compounds reduced the amount of ROS and preserved the integrity of the mitochondrial membrane. This is the first report of microbial transformation of cyclocephagenol (1).

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

Cited by 7 publications

References 44 publications

Genomics and metabolomics-based assessment of the biosynthetic potential of the sponge-associated microorganism Streptomyces cacaoi strain R2A-843A from the Philippines

Genomics and metabolomics-based assessment of the biosynthetic potential of the sponge-associated microorganism Streptomyces cacaoi strain R2A-843A from the Philippines

The role of Cycloastragenol at the intersection of Nrf-2/ARE, telomerase, and proteasome activity

Neuroprotective metabolites via fungal biotransformation of a novel sapogenin, cyclocephagenol

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