Comprehensive UPLC-MS/MS Profiling of Bioactive Phenolics and Their MYB Regulatory Networks in Wild and Cultivated Strawberries

Phenolic compounds are vital bioactive constituents in fruits, yet modern strawberry breeding has often reduced their diversity. Here, we employed a multi-omics approach integrating UPLC-MS/MS-based metabolomics and RNA-seq transcriptomics to investigate the divergence in phenolic profiles and their transcriptional regulation between a wild strawberry ( Fragaria nilgerrensis , HM) and three cultivated varieties (white ‘Danxue’ (DX), pink ‘Fenyu’ (FY), and red ‘Red Face 99’ (RF)). The wild HM genotype exhibited higher antioxidant activity and a significantly more complex phenolic profile, dominated by high-abundance galloylated and benzoylated glucosides (e.g., digallic acid methyl ester, salicylic acid-2- O -glucoside) that were largely absent or depleted in cultivated fruits. In contrast, the cultivated varieties displayed specialized yet simplified profiles: DX accumulated hydroxycinnamoyl galactonic acids, FY was enriched in feruloylated glucosides, and RF was characterized by coumaroyl-glucose derivatives. Transcriptomic analysis identified a set of MYB transcription factors (e.g., FxaYL_531g0581170 , FxaYL_642g0175720 ) significantly upregulated in wild HM, with strong correlations to key bioactive phenolics such as 4-hydroxybenzoate and salicylic acid derivatives. These findings illustrate how selective breeding has reshaped phenolic composition through alterations in MYB regulatory networks. The wild strawberry germplasm thus represents a valuable natural reservoir for biofortification strategies aimed at restoring the nutritional and functional quality of modern strawberry cultivars.