Artemisinin-based combination therapy (ACT) forms the first line of malaria treatment. However, the yield fluctuation of artemisinin has remained an unsolved problem in meeting the global demand for ACT. This problem is mainly caused by the glandular trichome (GT)-specific biosynthesis of artemisinin in all currently used Artemisia annua cultivars. Here, we report that non-GT cells of self-pollinated inbred A. annua plants can express the artemisinin biosynthetic pathway. Gene expression analysis demonstrated the transcription of six known pathway genes in GT-free leaves and calli of inbred A. annua plants. LC–qTOF–MS/MS analysis showed that these two types of GT-free materials produce artemisinin, artemisinic acid, and arteannuin B. Detailed IR-MALDESI image profiling revealed that these three metabolites and dihydroartemisinin are localized in non-GT cells of leaves of inbred A. annua plants. Moreover, we employed all the above approaches to examine artemisinin biosynthesis in the reported A. annua glandless (gl) mutant. The resulting data demonstrated that leaves of regenerated gl plantlets biosynthesize artemisinin. Collectively, these findings not only add new knowledge leading to a revision of the current dogma of artemisinin biosynthesis in A. annua but also may expedite innovation of novel metabolic engineering approaches for high and stable production of artemisinin in the future.

基于青蒿素的联合疗法（ACT）构成了疟疾治疗的第一线。然而，青蒿素的产量波动仍然不能满足全球对ACT的需求。这个问题主要是由青蒿素在所有当前使用的青蒿品种中的腺毛（GT）特异性生物合成引起的。在这里，我们报告说，自花授粉的A. annua植物的非GT细胞可以表达青蒿素的生物合成途径。基因表达分析表明无GT叶片和近交A.annua愈伤组织中六个已知途径基因的转录植物。LC–qTOF–MS / MS分析表明，这两种不含GT的物质均产生青蒿素，青蒿酸和青蒿素B。详细的IR-MALDESI图像分析表明，这三种代谢物和二氢青蒿素位于叶片的非GT细胞中自交的A. annua植物。此外，我们采用了所有上述方法来检查已报道的无花青蒿腺体（gl）突变体中青蒿素的生物合成。所得数据表明，再生的gl幼苗的叶片可生物合成青蒿素。总的来说，这些发现不仅增加了新知识，导致修订了青蒿中目前青蒿素生物合成的教条。 但将来也可能会加快新的代谢工程方法的创新，以使青蒿素的产量更高且稳定。