Metabolomics and transcriptomics reveal the mechanism of alkaloid synthesis in Corydalis yanhusuo bulbs

Corydalis yanhusuo W.T. Wang is a traditional herb. Benzylisoquinoline alkaloids (BIAs) are the main pharmacological active ingredients that play an important role in sedation, relieving pain, promoting blood circulation, and inhibiting cancer cells. However, there are few studies on the biosynthetic pathway of benzylisoquinoline alkaloids in Corydalis yanhusuo, especially on some specific components, such as tetrahydropalmatine. We carried out widely targeted metabolome and transcriptomic analyses to construct the biosynthetic pathway of benzylisoquinoline alkaloids and identified candidate genes. In this study, 702 metabolites were detected, including 216 alkaloids. Protoberberine-type and aporphine-type alkaloids are the main chemical components in C. yanhusuo bulbs. Key genes for benzylisoquinoline alkaloids biosynthesis, including 6-OMT, CNMT, NMCH, BBE, SOMT1, CFS, SPS, STOX, MSH, TNMT and P6H, were successfully identified. There was no significant difference in the content of benzylisoquinoline alkaloids and the expression level of genes between the two suborgans (mother-bulb and son-bulb). The expression levels of BIA genes in the expansion stage (MB-A and SB-A) were significantly higher than those in the maturity stage (MB-C and SB-C), and the content of benzylisoquinoline alkaloids was consistent with the pattern of gene regulation. Five complete single genes were likely to encode the functional enzyme of CoOMT, which participated in tetrahydropalmatine biosynthesis in C. yanhusuo bulbs. These studies provide a strong theoretical basis for the subsequent development of metabolic engineering of benzylisoquinoline alkaloids (especially tetrahydropalmatine) of C. yanhusuo.