Examinando por Materia "Metabolomics"

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Chemical modulation of the metabolism of an endophytic fungal strain of Cophinforma mamane using epigenetic modifiers and amino-acids
(El Sevier, 2022-05) Pacheco Tapia, R.; Vásquez Ocmín, Pedro; Duthen, S.; Ortíz, S.; Jargeat, P.; Amasifuen Guerra, Carlos Alberto; Haddad, Mohamed; Vansteelandt, Marieke
Endophytic fungi are capable of producing a great diversity of bioactive metabolites. However, the presence of silent and lowly expressed genes represents a main challenge for the discovery of novel secondary metabolites with different potential uses. Epigenetic modifiers have shown to perturb the production of fungal metabolites through the induction of silent biosynthetic pathways leading to an enhanced chemical diversity. Moreover, the addition of bioprecursors to the culture medium has been described as a useful strategy to induce specific biosynthetic pathways. The aim of this study was to assess the effects of different chemical modulators on the metabolic profiles of an endophytic fungal strain of Cophinforma mamane (Botryosphaeriaceae), known to produce 3 thiodiketopiperazine (TDKP) alkaloids (botryosulfuranols A-C), previously isolated and characterized by our team. Four epigenetic modifiers, 5-azacytidine (AZA), sodium butyrate (SB), nicotinamide (NIC), homoserine lactone (HSL) as well as 2 amino acids, L-phenylalanine and L-tryptophan, as bioprecursors of TDKPs, were used. The metabolic profiles were analysed by UHPLC-HRMS/MS under an untargeted metabolomics approach. Our results show that the addition of the two amino acids in C. mamane culture and the treatment with AZA significantly reduced the production of the TDKPs botryosulfuranols A, B and C. Interestingly, the treatment with HSL significantly induced the production of different classes of diketopiperazines (DKPs). The treatment with AZA resulted as the most effective epigenetic modifier for the alteration of the secondary metabolite profile of C. mamane by promoting the expression of cryptic genes.
Untargeted metabolomics to evaluate antifungal mechanism: a study of Cophinforma mamane and Candida albicans interaction
(Springer, 2023-01-03) Triastuti, Asih; Vansteelandt, Marieke; Barakat, Fatima; Amasifuen Guerra, Carlos Alberto; Jargeat, Patricia; Haddad, Mohamed
Microbial interactions between filamentous fungi and yeast are still not fully understood. To evaluate a potential antifungal activity of a filamentous fungus while highlighting metabolomic changes, co-cultures between an endophytic strain of Cophinforma mamane (CM) and Candida albicans (CA) were performed. The liquid cultures were incubated under static conditions and metabolite alterations during the course were investigated by ultra-performance liquid chromatography–tandem mass spectrophotometry (UPLC–MS/MS). Results were analyzed using MS-DIAL, MS-FINDER, METLIN, Xcalibur, SciFinder, and MetaboAnalyst metabolomics platforms. The metabolites associated with catabolic processes, including the metabolism of branched-chain amino acids, carnitine, and phospholipids were upregulated both in the mono and co-cultures, indicating fungal adaptability to environmental stress. Several metabolites, including C20 sphinganine 1-phosphate, myo-inositol, farnesol, gamma-undecalactone, folinic acid, palmitoleic acid, and MG (12:/0:0/0:0) were not produced by CA during co-culture with CM, demonstrating the antifungal mechanism of CM. Our results highlight the crucial roles of metabolomics studies to provide essential information regarding the antifungal mechanism of C. mamane against C. albicans, especially when the lost/undetected metabolites are involved in fungal survival and pathogenicity.