Samsoniella hepiali produces an array of pharmacologically valuable metabolites, but how environmental pH regulates its antioxidant system and lipid metabolism during submerged fermentation remains unclear. This study aimed to investigate the effects of different initial culture pH values (pH 4, 5, 6, and 7) on the antioxidant capacity and lipidomic metabolism of S. hepiali. The results demonstrated that at pH 5, the activities of peroxidase (POD) and superoxide dismutase (SOD), the contents of total phenolics (TP) and flavonoids, the scavenging rates of DPPH• and •OH, and the total antioxidant capacity all peaked. Conversely, the level of glutathione (GSH) reached its maximum at pH 6 (0.69 ± 0.014 μmol/g). Lipidomic analysis identified a total of 404 lipid molecular species, mainly TG, PE, and DG. Comparative analysis among pH 4 vs. pH 5, pH 6 vs. pH 5, and pH 7 vs. pH 5 revealed 27 core DALs belonging to 11 lipid subclasses, most of which were upregulated at pH 5. KEGG pathway enrichment analysis further revealed that sphingolipid metabolism was the sole core co-enriched pathway under different pH conditions. Particularly at pH 5, key signaling lipids, such as ceramides, underwent pronounced targeted accumulation. This study elucidates the molecular adaptation mechanisms of medicinal fungi in response to pH variation from a lipidomic perspective. It provides a basis for optimizing fermentation conditions to enhance antioxidant activity and functional lipid production.
Tong et al. (Sat,) studied this question.