Multi-perspective integration reveals the molecular and microbiological basis for differences in the biosynthesis of phenylpropanoid-related bioactive compounds in different medicinal parts of Angelica sinensis (Oliv.) Diels.

Angelica sinensis (Oliv.) Diels (Ang) is a major medicinal herb, and its phenylpropanoids constitute the key bioactive compounds. However, the molecular and microbiological basis underlying their accumulation remains unclear, particularly at the sub-regional level of root head, body, and tail (ARH, ARB and ART, respectively). To address this, we integrated whole-genome gene family analysis, differential gene expression profiling, network pharmacology, molecular docking, microbial community characterization, and mediation regression path analysis to systematically investigate the compositional differences across different root regions. The results indicated that phenylpropanoid biosynthesis and plant-pathogen interaction pathways were significantly enriched in ART. Eight key phenylpropanoid biosynthetic gene families were identified, the majority of which showed predominant expression in ART. Metabolic profiling further demonstrated that prenyl arabinosyl-(1 → 6)-glucoside, coumarin, and lawsone were markedly enriched in ART compared to both ARH and ARB, along with several other metabolites. Network pharmacology and molecular docking revealed that ART-enriched phenylpropanoid-related metabolites constitute a multi-target network, many of which exhibited anti-thrombotic, anti-blood-stasis, and anti-inflammatory activities. Microbiome profiling showed that dominant endophytic fungi reached their highest relative abundance in ART, with community assembly governed deterministically. Mediation regression path analysis further statistically supported that highly expressed phenylpropanoid biosynthetic genes in ART positively modulate phenylpropanoid-related metabolites, and these genes exerted a significant mediating effect on the shaping of metabolites by endophytic fungi. Overall, this study established a multidimensional analytical framework to elucidate the molecular and microbial basis for the preferential accumulation of phenylpropanoid-related metabolites in ART, offering new insights for precision medicine and quality control of Ang.