AaSPATULA synergistically coordinates glandular trichome initiation and vegetative growth to maximize whole-plant artemisinin yield in Artemisia annua

Plant development and specialized metabolism are tightly coordinated, yet the molecular mechanisms that couple vegetative growth with artemisinin biosynthesis in Artemisia annua remain largely elusive. This knowledge gap has hindered the development of rational strategies to maximize artemisinin yield. Here, we identify AaSPATULA, a novel bHLH transcription factor, as an integrator that simultaneously promotes glandular secretory trichome (GST) initiation and leaf development. Overexpression of AaSPATULA markedly increased GST density, resulting in significant artemisinin accumulation. Mechanistically, AaSPATULA interacts with the HD-ZIP transcription factor AaHD8 to directly activate the trichome regulator AaGSW2, thereby driving GST formation. Remarkably, AaSPATULA also positively regulates vegetative growth: overexpression lines displayed enhanced leaf expansion and increased biomass, which together dramatically boosted whole-plant artemisinin yield, whereas RNAi lines showed stunted growth and reduced artemisinin production. Integrated transcriptomic and metabolomic profiling revealed that AaSPATULA upregulates photosynthesis-related genes and enhances primary carbon metabolism. Collectively, these findings establish AaSPATULA as a key molecular hub that synergistically couples vegetative biomass production with artemisinin-producing glandular trichomes, providing a new framework for developmental-metabolic engineering to improve the yield of high-value medicinal compounds in plants.