Differential Analysis of Sesquiterpenoids of Atractylodes macrocephalus from Different Origins Based on Transcriptomics.

Atractylodes macrocephala (A.M.) is a traditional Chinese medicinal and edible herb renowned for its spleen-tonifying, dampness-resolving, diuretic, and antiperspirant properties. Its primary bioactive constituents are terpenoids, which have demonstrated anti-inflammatory, antitumor, and immunomodulatory activities. However, transcriptomic studies focusing on terpenoid biosynthesis in A.M. from different geographical origins remain limited. To investigate the molecular mechanisms underlying differential sesquiterpenoid production, we performed transcriptome sequencing on samples collected from four distinct regions in China. Sesquiterpenoid biosynthesis predominantly proceeds through the mevalonate (MVA) and methylerythritol phosphate (MEP) pathways. Comparative analysis revealed four key enzyme-encoding genes-HMGCR, ISPF, GCPE, and FDPS-whose differential expression patterns were further validated by quantitative real-time PCR (qRT-PCR). Samples from Shaanxi exhibited the highest upregulation of biosynthetic genes and the greatest enrichment of terpene-related metabolites, suggesting enhanced pharmacological potential. In contrast, samples from Fujian, Anhui, and Hebei displayed relatively lower activity, with only FDPS upregulated in the Hebei sample. High-performance liquid chromatography (HPLC) quantification confirmed regional differences in the levels of major terpenoids-including atractylodin, atractylenolide I, and atractylenolide III-which correlated well with the observed gene expression profiles. This study compared conspecific A.M. from different geographical regions and further revealed that the variation in terpenoid metabolites is closely related to environmental factors. These findings provide a theoretical basis for the further discovery of functional genes and offer important implications for the quality control of A.M.