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

Artemisinin, a crucial antimalarial compound synthesized in <i>Artemisia annua</i>, 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 <i>AaMYB121</i> in transgenic <i>A. annua</i> 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 <i>DBR2</i> (-1146~-1103) and <i>ALDH1</i> (-1558~-1504), thereby triggering the transcriptional initiation of these genes. Notably, AaMYB121 features an elongated DNA-binding domain that specifically recognizes AT-rich <i>cis</i>-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.