Groppi E, Gadea A, Monge C, Cristofoli V, Vansteelandt M, Haddad M
UMR 152 Pharma CDev, Université de Toulouse, IRD, UPS, Toulouse, France.
Int J Microbiol. 2024 Oct 28;2024:1763495. doi: 10.1155/2024/1763495. eCollection 2024.
Toxigenic fungi are capable of producing toxic metabolites, called mycotoxins. But the presence of silent and lowly expressed genes represents the main challenge for the discovery of novel mycotoxins, especially their lesser-known forms, commonly referred to as "emerging mycotoxins." Epigenetic modifiers (EMs) are compounds that are able to alter the production of metabolites through the induction of silent biosynthetic pathways leading to an enhanced chemical diversity. The aim of this study was to assess the effects of different chemical modulators on the metabolic profiles of the well-known toxigenic fungal species, . Four EMs, 5-azacytidine, sodium butyrate, nicotinamide (NIC), and sodium valproate (SV), were used. Following their addition to cultures, the metabolic profiles were analyzed by using UHPLC-HRMS/MS under targeted and untargeted metabolomics approaches. Metabolites were putatively annotated through the use of MS-DIAL and MS-FINDER. Our results show that the treatment with SV induced the most important alteration of the secondary metabolic profile of , by promoting the expression of cryptic genes. Among the 50 most discriminating metabolites across five culture conditions, 12 were fusarins or fusarin analogs. In contrast, SB and NIC had little impact on these metabolites. The study highlights SV's ability to alter gene expression by inhibiting DNA deacetylation in fungal strains. This research could have significant implications for agriculture and food industry, especially in regions facing major mycotoxin challenges.
产毒真菌能够产生被称为霉菌毒素的有毒代谢产物。但是沉默和低表达基因的存在是发现新型霉菌毒素的主要挑战，尤其是那些鲜为人知的形式，通常被称为“新兴霉菌毒素”。表观遗传修饰剂（EMs）是一类能够通过诱导沉默的生物合成途径来改变代谢产物的产生，从而增加化学多样性的化合物。本研究的目的是评估不同化学调节剂对著名产毒真菌物种代谢谱的影响。使用了四种表观遗传修饰剂，即5-氮杂胞苷、丁酸钠、烟酰胺（NIC）和丙戊酸钠（SV）。将它们添加到培养物中后，采用靶向和非靶向代谢组学方法，通过超高效液相色谱-高分辨质谱/质谱（UHPLC-HRMS/MS）分析代谢谱。通过使用MS-DIAL和MS-FINDER对代谢产物进行了推定注释。我们的结果表明，用丙戊酸钠处理通过促进隐秘基因的表达，诱导了该真菌次级代谢谱的最重要变化。在五种培养条件下最具区分性的50种代谢产物中，有12种是镰刀菌素或镰刀菌素类似物。相比之下，丁酸钠和烟酰胺对这些代谢产物影响很小。该研究突出了丙戊酸钠通过抑制真菌菌株中的DNA去乙酰化来改变基因表达的能力。这项研究可能对农业和食品工业具有重大意义，尤其是在面临主要霉菌毒素挑战的地区。
