AaMYB121, a Novel R2-MYB-like Transcription Factor, Regulates Artemisinin Biosynthesis in Artemisia annua

Artemisinin, a crucial antimalarial compound synthesized in Artemisia annua, is tightly controlled by various transcription factors. Despite significant progress in understanding this regulatory network, further exploration of additional factors is needed to improve artemisinin biosynthesis. Here, we identified a novel R2-MYB-like transcription factor, AaMYB121, which responds to methyl jasmonate (MeJA). Overexpression of AaMYB121 in transgenic A. annua plants resulted in dihydroartemisinic acid (DHAA) content being elevated 2~3 times compared to the control, while artemisinin levels increased to 1.4~2 times, significantly boosting artemisinin biosynthesis. Dual-Luciferase (Dual-LUC) assay and yeast one-hybrid (Y1H) analysis demonstrated that AaMYB121 directly binds to the promoter motifs of DBR2 (-1146~-1103) and ALDH1 (-1558~-1504), thereby triggering the transcriptional initiation of these genes. Notably, AaMYB121 features an elongated DNA-binding domain that specifically recognizes AT-rich cis-elements in the promoters of key artemisinin biosynthetic genes. These findings established AaMYB121 as a novel MYB-like transcription factor with strong potential to enhance the regulation of artemisinin production through targeted modulation, offering a valuable approach to improve artemisinin yields for therapeutic purposes.