Cercospora sp. as a source of anti-aging polyketides targeting 26S proteasome and scale-up production in submerged bioreactor

Georgousaki, K; Tsafantakis, Nikolaos; Gumeni, Sentiljana; González-Menéndez, Víctor; Pedro, Nuria de; Tormo, José R.; Almeida, Celso; Lambert, Carole; Genilloud, Olga; Trougakos, Ioannis P.; Fokialakis, Nikolas

doi:10.1016/j.jbiotec.2019.05.015

Cited by 4 publications

(4 citation statements)

References 44 publications

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“…The flask was incubated in a shaking incubator at 220 rpm, at 22 • C and 70% relative humidity. After 7 days of incubation, a 3 mL aliquot of the inoculum was used to inoculate ten flasks of the production medium Dex-Soy [22]. The flasks (100 mL medium per 500 mL Erlenmeyer flask) were incubated in a shaking Khüner incubator at 220 rpm, 22 • C and 70% of relative humidity for 14 days.…”

Section: Fermentation and Extractionmentioning

confidence: 99%

“…Measurement of proteasome proteolytic activities was performed as previously described [22,56]. Briefly, human fibroblasts were plated in 60-mm dishes and were treated for 24 h with a concentration of 5 µM for each compound and 1 µg/mL and 10 µg/mL of concentration for each extract.…”

Section: Proteasome Activitymentioning

confidence: 99%

“…Natural compounds are recognized for their broad range of biological activities with numerous applications in health and disease treatment [19][20][21]. In continuation of our studies in microbial derived bioactive metabolites, we investigated the strain B. adusta CF-092983 as a potential source of natural products that are able to enhance UPP and ALP functionalities and thus to contribute to the maintenance of proteome stability affected by several exogenous and/or endogenous factors [22].…”

Section: Introductionmentioning

confidence: 99%

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Biological Evaluation and In Silico Study of Benzoic Acid Derivatives from Bjerkandera adusta Targeting Proteostasis Network Modules

et al. 2020

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A main cellular functional module that becomes dysfunctional during aging is the proteostasis network. In the present study, we show that benzoic acid derivatives isolated from Bjerkandera adusta promote the activity of the two main protein degradation systems, namely the ubiquitin-proteasome (UPP) and especially the autophagy-lysosome pathway (ALP) in human foreskin fibroblasts. Our findings were further supported by in silico studies, where all compounds were found to be putative binders of both cathepsins B and L. Among them, compound 3 (3-chloro-4-methoxybenzoic acid) showed the most potent interaction with both enzymes, which justifies the strong activation of cathepsins B and L (467.3 ± 3.9%) on cell-based assays. Considering that the activity of both the UPP and ALP pathways decreases with aging, our results suggest that the hydroxybenzoic acid scaffold could be considered as a promising candidate for the development of novel modulators of the proteostasis network, and likely of anti-aging agents.

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Section: Fermentation and Extractionmentioning

confidence: 99%

Section: Proteasome Activitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Biological Evaluation and In Silico Study of Benzoic Acid Derivatives from Bjerkandera adusta Targeting Proteostasis Network Modules

et al. 2020

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“…The first set of fermentations was performed in duplicate in vials (40 mL EPA vials) and 250 mL Erlenmeyer flasks containing 10 and 50 mL of medium respectively. Fungal inocula cultured in SMYA medium during 7 days at 22 °C, 220 rpm and 70% relative humidity were used to inoculate EPA vials and Flasks at 3% of final volume (v/v) following previously described protocols 20 , 39 . All fermentation broths were incubated for 7, 14 and 21 days, in order to investigate the best time course of the production of the bioactive metabolites.…”

Section: Methodsmentioning

confidence: 99%

Comoclathrin, a novel potent skin-whitening agent produced by endophytic Comoclathris strains associated with Andalusia desert plants

Georgousaki

González-Menéndez

Tormo

et al. 2022

Sci Rep

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As part of our screening program for the discovery of molecules of microbial origin with skin-whitening activity, 142 diverse fungal endophytes from a wide variety of Andalusia arid plants were screened, applying the OSMAC approach. The fungal strains CF-090361 and CF-090766, isolated from xerophytic plants, were selected as the most promising, while phylogenetic analysis revealed that both strains could represent a new species within the genus Comoclathris. The effect of different fermentation conditions on the production of tyrosinase inhibitory activity was examined, in order to identify the optimum cultivation conditions. LCMS based metabolomics was applied to determine significant differences between the strains and fermentation conditions, and to identify potential bioactive secondary metabolites. Bioassay-guided purification of the main active components led to the isolation of three new compounds (1–3), along with the known compounds graphostrin B (4) and brevianamide M (5). Compound 1 (Comoclathrin) demonstrated the strongest anti-tyrosinase activity (IC50 0.16 μΜ), which was 90-times higher than kojic acid (IC50 14.07 μΜ) used as positive control. Additionally, comoclathrin showed no significant cytotoxicity against a panel of cancer cell lines (HepG2, A2058, A549, MCF-7 and MIA PaCa-2) and normal BJ fibroblasts. These properties render comoclathrin an excellent development candidate as whitening agent.

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A Secondary Metabolite of Cercospora sp., Associated with Rosa damascena Mill., Inhibits Proliferation, Biofilm Production, Ergosterol Synthesis and Other Virulence Factors in Candida albicans

et al. 2022

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Cercospora sp. as a source of anti-aging polyketides targeting 26S proteasome and scale-up production in submerged bioreactor

Cited by 4 publications

References 44 publications

Biological Evaluation and In Silico Study of Benzoic Acid Derivatives from Bjerkandera adusta Targeting Proteostasis Network Modules

Biological Evaluation and In Silico Study of Benzoic Acid Derivatives from Bjerkandera adusta Targeting Proteostasis Network Modules

Comoclathrin, a novel potent skin-whitening agent produced by endophytic Comoclathris strains associated with Andalusia desert plants

A Secondary Metabolite of Cercospora sp., Associated with Rosa damascena Mill., Inhibits Proliferation, Biofilm Production, Ergosterol Synthesis and Other Virulence Factors in Candida albicans

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