Comparative phytochemical profiling and meta‑analysis of public transcriptomic datasets uncover species‑ and organ‑specific patterns of flavonoid and phenolic biosynthesis in Ferula species

Understanding the molecular basis of flavonoid and phenolic biosynthesis across Ferula species is essential for elucidating their metabolic diversity and pharmacological potential. In the present study, a comparative multi‑omics analysis was conducted on F. persica, F. gummosa, and F. assa‑foetida by integrating high‑performance liquid chromatography (HPLC; three biological replicates per tissue) with publicly available RNA sequencing data to explore putative biochemical mechanisms. HPLC profiling revealed marked interspecies and organ‑specific differences; notably, flowers of F. assa‑foetida accumulated higher chlorogenic acid (272.28 ± 5.92 µg/g) and rutin (395.24 ± 6.46 µg/g) compared with the leaves of F. persica and roots of F. gummosa, which exhibited substantially lower concentrations of these metabolites. Transcriptomic analysis identified distinct co-expression modules (MEcyan and MEsalmon) that were strongly correlated with metabolite profiles, suggesting distinct transcriptional patterns associated with biochemical diversity. KEGG pathway enrichment further revealed divergent biosynthetic trajectories among species: ANS expression was detected exclusively in F. assa‑foetida flowers, whereas CYP71D9 expression was specific to F. gummosa, reflecting lineage‑associated metabolic specialization. In contrast, core pathway genes such as CHI, F3H, FLS, CYP81E, and CYP75B1 were consistently expressed across all species, indicating a conserved biosynthetic backbone. These combined analyses provide a mechanistic framework for understanding metabolic specialization in Ferula species and offer a foundation for future studies aimed at the sustainable utilization of medicinal plant genetic resources.