A novel synergistic regulatory mechanism involving the MYB39-MYB111-bHLH51-TTG1 module in the phenolic and diterpenoid biosynthetic pathways of Salvia miltiorrhiza.

Plants produce a variety of secondary metabolites, and their biosynthesis is often regulated by multiple transcription factors. However, the potential connections between the biosynthesis of different types of metabolites remain unclear. In this study, we present a novel mechanism in which the MYB39-MYB111-bHLH51-TTG1 module synergistically regulates both the phenolic and diterpenoid biosynthetic pathways in the medicinal model plant Salvia miltiorrhiza. SmMYB39 acts as a repressor, while the MYB111-bHLH51-TTG1 (SmMBW) complex functions as an activator of these pathways. SmMYB39 interferes with the formation of the SmMBW complex by interacting with all its components. Additionally, SmMYB39 inhibits the transcriptional activity of SmbHLH51 on its target genes. Expression of SmMYB39 is suppressed by exogenous MeJA, whereas the expressions of SmbHLH51, SmMYB111 and SmTTG1 are induced. Furthermore, SmMYB39 interacts with SmJAZ1, a core repressor in the jasmonic acid (JA) signalling pathway. These findings suggest that the SmMYB39-SmMBW module mediates JA signalling and synergistically regulates the biosynthesis of phenolics and diterpenoids in S. miltiorrhiza. Our findings offer important insights into the coordinated regulatory mechanisms of transcription activators and repressors that control distinct metabolic pathways in plants.