@article {Georgousaki2019,
	title = {{Cercospora sp. as a source of anti-aging polyketides targeting 26S proteasome and scale-up production in submerged bioreactor}},
	journal = {Journal of Biotechnology},
	volume = {301},
	number = {January},
	year = {2019},
	month = {aug},
	pages = {88{\textendash}96},
	publisher = {Elsevier},
	abstract = {From a large screening of microbial extracts for the discovery of proteasome modulating natural products, the fungal strain Cercospora sp. (CF-223709) was selected as the most promising for further investigation. Different liquid cultures of the strain were initially screened for their anti-oxidant activity (DPPH, ABTS) and for their cytotoxicity against the A2058, HepG2 and CCD25sk cell lines. A detailed chemical analysis and evaluation of the capacity to activate 26S-proteasome was followed for the most active extract. Three main polyketides were isolated and characterized by extensive analysis of NMR and HRMS spectra data as penialidine F (1), fulvic acid (2), and SB238569 (3). Fulvic acid showed the most significant anti-oxidant activity. Its IC50 value (8.16 $μ$M) against the ABTS radical resulted 3-fold lower than the standard trolox. Fulvic acid also demonstrated a significant effect on proteasome by enhancing the chymotrypsin- and caspase-like activities of the 26S proteasome of human fibroblasts by 71.43{\%} and 37.5{\%} at 1 $μ$M, respectively. Furthermore by scaling up the culture in a 30 L submerged bioreactor, Cercospora sp. produced up to 162.6 {\textpm} 1.3 mg of fulvic acid/L. Our findings suggest that CF-223709 can be a promising source of proteasome activating natural compounds.},
	keywords = {Antioxidant activity, Bioreactor, Cercospora, Filamentous fungi, Polyketides, Proteasome},
	issn = {01681656},
	doi = {10.1016/j.jbiotec.2019.05.015},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S0168165619301798},
	author = {Georgousaki, Katerina and Tsafantakis, Nikolaos and Gumeni, Sentiljana and Gonz{\'a}lez-Men{\'e}ndez, Victor and de Pedro, Nuria and Tormo, Jos{\'e} Rub{\'e}n and Almeida, Celso and Lambert, Carole and Genilloud, Olga and Trougakos, Ioannis P. and Fokialakis, Nikolas}
}
