Endophytes drive the biosynthesis and accumulation of sesquiterpenoids in Atractylodes lancea (Thunb.) DC.

As a traditional medicinal plant, Atractylodes lancea (Thunb.) DC. has a wide range of therapeutic effects, and the sesquiterpenoids in rhizomes are the key medicinal basis. Endophytes influence the formation of plant metabolites. However, the intrinsic mechanism by which aboveground endophytes and belowground endophytes methodically influence the sesquiterpenoid biosynthesis in medicinal plants remains unknown. The two typical chemotypes of A. lancea , which differ in volatile oil, were selected to explore the role of endophytes on sesquiterpenoid biosynthesis using metabolomics and microbiome analyses. The results showed that differential crucial metabolites closely related to sesquiterpenoid synthesis were screened to be 40 in the rhizomes and 5 in the leaves. The diversity of endophytes had significant differences between different origins and tissues of A. lancea . Nocardiaceae and other endophytes in leaves of both A. lancea chemotypes activated primary metabolic and signaling pathways. The diversified sesquiterpenoids and precursors produced by both A. lancea chemotypes selected the specific endophytes in rhizomes. The specific endophytes such as Sphingomonadaceae and Bacillaceae in turn resulted in the different levels of the key components in the two A. lancea chemotypes, which were also confirmed in pot experiments. Overall, this research provides novel viewpoint into how microbes regulate the geoherbalism of A. lancea and offers a theoretical foundation for more efficient and rational utilization of endophytic microbial resources to regulate the constitution of active ingredients in cultivated medicinal plants in the future. • Endophytes in leaves activate primary metabolic pathways linked to sesquiterpenoid synthesis. • Sesquiterpenoids and their precursors select the specific endophytes in rhizomes. • Bacillus reduces the amounts of atractylone and atractylodin in rhizomes. • Sphingobium increases atractylone and atractylodin content, and reduces β-eudesmol content in rhizomes.