Yuan Mingyuan, Sheng Yinguo, Bao Jingjing, Wu Wenkai, Nie Guibin, Wang Lingjian, Cao Junfeng
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, China.
National Key Laboratory of Plant Molecular Genetics, CAS Center for Excellence in Molecular Plant Sciences/Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, 200032, China.
Plant Biotechnol J. 2025 Feb;23(2):315-332. doi: 10.1111/pbi.14449. Epub 2024 Aug 27.
Artemisinin, the well-known natural product for treating malaria, is biosynthesised and stored in the glandular-secreting trichomes (GSTs) of Artemisia annua. While numerous efforts have clarified artemisinin metabolism and regulation, the molecular association between artemisinin biosynthesis and GST development remains elusive. Here, we identified AaMYC3, a bHLH transcription factor of A. annua, induced by jasmonic acid (JA), which simultaneously regulates GST density and artemisinin biosynthesis. Overexpressing AaMYC3 led to a substantial increase in GST density and artemisinin accumulation. Conversely, in the RNAi-AaMYC3 lines, both GST density and artemisinin content were markedly reduced. Through RNA-seq and analyses conducted both in vivo and in vitro, AaMYC3 not only directly activates AaHD1 transcription, initiating GST development, but also up-regulates the expression of artemisinin biosynthetic genes, including CYP71AV1 and ALDH1, thereby promoting artemisinin production. Furthermore, AaMYC3 acts as a co-activator, interacting with AabHLH1 and AabHLH113, to trigger the transcription of two crucial enzymes in the artemisinin biosynthesis pathway, ADS and DBR2, ultimately boosting yield. Our findings highlight a critical connection between GST initiation and artemisinin biosynthesis in A. annua, providing a new target for molecular design breeding of traditional Chinese medicine.
青蒿素是一种著名的抗疟天然产物，在黄花蒿的腺毛分泌型腺毛（GSTs）中生物合成并储存。尽管众多研究已阐明青蒿素的代谢与调控，但青蒿素生物合成与腺毛发育之间的分子关联仍不清楚。在此，我们鉴定出黄花蒿的一个bHLH转录因子AaMYC3，它受茉莉酸（JA）诱导，可同时调控腺毛密度和青蒿素生物合成。过表达AaMYC3导致腺毛密度和青蒿素积累显著增加。相反，在RNA干扰AaMYC3的株系中，腺毛密度和青蒿素含量均显著降低。通过RNA测序以及体内和体外分析，AaMYC3不仅直接激活AaHD1转录，启动腺毛发育，还上调青蒿素生物合成基因的表达，包括CYP71AV1和ALDH1，从而促进青蒿素的产生。此外，AaMYC3作为共激活因子，与AabHLH1和AabHLH113相互作用，触发青蒿素生物合成途径中两种关键酶ADS和DBR2的转录，最终提高产量。我们的研究结果突出了黄花蒿中腺毛起始与青蒿素生物合成之间的关键联系，为中药分子设计育种提供了新靶点。
