DNA methylation regulates biosynthesis of tanshinones and phenolic acids during growth of Salvia miltiorrhiza.

This article investigates the role of DNA methylation in regulating the biosynthesis of tanshinones and phenolic acids—key active compounds—in the roots of Salvia miltiorrhiza, a medicinal plant used for cardiovascular treatments. Through targeted metabolite profiling, whole-genome bisulfite sequencing, and transcriptome analysis at three root growth stages (40, 60, and 90 days), the study found that tanshinone and phenolic acid contents increased with root development, coinciding with elevated DNA methylation levels, particularly in the CHH context. This hypermethylation correlated with increased expression of DNA methyltransferase genes (SmCMT2, SmDDM1, SmAGO4, SmDRM1) and altered expression of biosynthetic genes, where hypermethylation in gene bodies was associated with upregulated tanshinone and phenolic acid biosynthesis genes, and promoter hypermethylation corresponded with downregulation of a phenolic acid synthesis inhibitor gene. These findings highlight DNA methylation as an epigenetic mechanism influencing secondary metabolite accumulation during S. miltiorrhiza root growth, providing a foundation for molecular breeding strategies to enhance production of its bioactive compounds.