Transcriptomic and metabolomic insights into flavor variations in wild and cultivated Agaricus bisporus

Agaricus bisporus is a widely cultivated edible fungus globally. However, the mechanisms underlying the differences in flavor and nutritional traits between wild-type (W) and cultivated-type (C) strains remain unclear, which hinders the artificial breeding of high-quality varieties. This study systematically revealed, for the first time, the molecular and metabolic basis of flavor divergence between wild and cultivated A. bisporus by integrating transcriptomics and metabolomics. A total of 43 strains (23 wild-type and 20 cultivated-type) were analyzed using high-throughput sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to dissect differences in gene expression and metabolite profiles. Results showed that although total protein and amino acid contents exhibited no significant differences, transcriptomic analysis identified significant upregulation of AGABI2DRAFT_188981 and AGABI2DRAFT_191000 (genes associated with high-affinity methionine permease MUP1) in cultivated strains, suggesting their indirect regulation of flavor formation via methionine metabolism. Metabolomic analysis further revealed a marked increase in uridine levels in cultivated strains (3.2-fold higher than wild-type, p < 0.01), indicating potential medicinal value, while wild strains were enriched with flavor precursors such as fumaric acid and isoleucine (fold change ≥ 2.5). In contrast, cultivated strains accumulated metabolites like 2-hydroxybutyric acid and α-ketoglutarate (VIP > 1.5). This study pioneered the construction of a gene-metabolite correlation network, identifying a strong positive correlation between AGABI2DRAFT_191352 (6-phosphofructokinase) and 2-hydroxybutyric acid (r = 0.82), highlighting the regulatory role of glycolytic flux in flavor metabolism. These findings not only elucidate the impact of artificial cultivation on metabolic reprogramming in A. bisporus but also provide critical molecular targets for targeted breeding of strains with enhanced flavor and nutritional value, offering practical significance for advancing the edible fungi industry.