bHLH130 mediates gibberellin signaling to regulate tanshinone biosynthesis in Salvia miltiorrhiza

Salvia miltiorrhiza is a prominent traditional Chinese medicinal (TCM) herb with notable therapeutic applications, especially in treatment of cardiovascular and cerebrovascular diseases. A crucial role in promoting tanshinone biosynthesis is attributed to the gibberellic acid (GA) signaling pathway; however, its precise regulatory mechanisms remain incompletely understood. In the current investigation, we identified bHLH130, a GA-responsive bHLH transcription factor (TF), via transcriptomic analysis of GA-treated hairy roots from S. miltiorrhiza . Functional analysis demonstrated that bHLH130 overexpression markedly suppressed tanshinone biosynthesis, whereas its knockout resulted in elevated tanshinone accumulation. Additionally, it was confirmed that bHLH130 directly targets E-box motifs within the promoters of biosynthetic genes, including DXS2 , CPS1 , KSL1 , and CYP76AH1 , thereby negatively regulating their transcriptional activities. Moreover, bHLH130 interacts with DELLA4, forming a regulatory complex implicated in the modulation of tanshinone biosynthesis. Co-overexpression assays revealed that DELLA4 attenuated the inhibitory effects of bHLH130 on tanshinone accumulation. Collectively, our data propose that the bHLH130‒DELLA4 interaction constitutes a critical regulatory node, balancing GA signaling with secondary metabolite production and offering novel strategies for the metabolic engineering of tanshinones. In conclusion, this research delineates the regulatory role of bHLH130 in tanshinone synthesis, providing valuable insights into the GA-mediated modulation of secondary metabolism. Gibberellins (GA) inhibit bHLH130 to promote tanshinone biosynthesis; however, it also degrades DELLA to release bHLH130 to repress tanshinone accumulation. This dual regulatory mechanism ensures that the levels of tanshinone are tightly regulated.