Integrated metabolomics and transcriptomics investigate the bulb-specific biosynthesis of medicinal steroidal alkaloids in Fritillaria taipaiensis

BACKGROUND: Fritillaria taipaiensis is a commercially important medicinal herb, the bulbs of which are a valued source of steroidal alkaloids with potent antitussive and expectorant properties. However, the mechanisms underlying the tissue-specific biosynthesis of these bioactive compounds remain poorly understood, limiting strategies for their enhanced production. RESULTS: This study, we integrated UPLC-MS/MS-based metabolomics with multi-tissue transcriptomics to elucidate the steroidal alkaloid biosynthetic pathway in F. taipaiensis. Comparative metabolomic profiling revealed distinct tissue-specific accumulation patterns, with bulbs serving as the primary site for therapeutically relevant steroidal alkaloids such as peimisine, edpetiline, and delafrine. Transcriptomic analysis unveiled metabolic compartmentalization, characterized by the bulb-specific upregulation of mevalonate (MVA) pathway genes, contrasting with leaf-predominant expression of methylerythritol phosphate (MEP) pathway components. This indicates a tissue-specific partitioning of precursor supply. Of note, we identified bulb-specific isoforms FrtSSR1 (encoding a Δ²⁴(²⁵)-reductase) and FrtSMO1-1 (encoding a C-4 demethylase), which were highly expressed and are proposed to pivotal roles in redirecting metabolic flux toward cholesterol biosynthesis. Furthermore, the coordinated induction of cytochrome P450 enzymes in bulbs suggests their involvement in mediating structural diversification of the steroidal skeleton. CONCLUSIONS: Our findings systematically unravel the molecular basis of bulb-specific steroidal alkaloid accumulation, highlighting pathway specialization, enzyme subfunctionalization, and CYP450-mediated modification. This study provides a genetic foundation and key candidate genes for future metabolic engineering and molecular breeding strategies aimed at improving the yield of high-value steroidal alkaloids in Fritillaria species.