Metabolomic and Transcriptomic Insights into Enhanced Paclitaxel Biosynthesis in Cultivated <i>Taxus cuspidata</i>

Taxus cuspidata, a rare species of the Taxus genus, and its wild resources are under severe threat. The development of cultivated species has become an important strategy to replace wild species. The objective of this work was to elucidate the differences in secondary metabolite accumulation, particularly in the paclitaxel biosynthesis pathway, between wild and cultivated species. This study employed liquid chromatography-tandem mass spectrometry (LC-MS/MS) and RNA sequencing (RNA-Seq) technologies to conduct integrated metabolomic and transcriptomic analyses of wild and cultivated species of T. cuspidata. The results showed that the content of paclitaxel in cultivated species was significantly higher than in wild species, reaching 1.67 times that of the latter (p < 0.01). Additionally, the content of key paclitaxel precursors, GGPP and 10-deacetylbaccatin III, in cultivated species was 1.94 times (p < 0.05) and 1.71 times (p < 0.01) higher than in wild species, respectively. Transcriptomic analysis identified 2606 differentially expressed genes (DEGs), among which key enzyme genes related to paclitaxel biosynthesis (such as DXS, DXR, GGPS, etc.) were generally upregulated in cultivated species. Multiple key enzyme genes in both the 2-C-methyl-D-erythritol 4-phosphate pathway (MEP) and paclitaxel biosynthesis pathways were significantly upregulated in cultivated species. Conversely, genes and metabolites related to sugar metabolism were found to be higher in content in wild species. These findings reveal the significant advantage of cultivated species in paclitaxel production capacity, providing new insights into the metabolic regulation mechanisms during yew domestication. This has important implications for optimizing paclitaxel biosynthesis and guiding future improvements in T. cuspidata cultivars.