Jasmonate promotes artemisinin biosynthesis by activating the TCP14-ORA complex in <i>Artemisia annua</i>.

Abstract

<i>Artemisia annua</i> produces the valuable medicinal component, artemisinin, which is a sesquiterpene lactone widely used in malaria treatment. AaORA, a homolog of CrORCA3, which is involved in activating terpenoid indole alkaloid biosynthesis in <i>Catharanthus roseus</i>, is a jasmonate (JA)-responsive and trichome-specific APETALA2/ETHYLENE-RESPONSE FACTOR that plays a pivotal role in artemisinin biosynthesis. However, the JA signaling mechanism underlying AaORA-mediated artemisinin biosynthesis remains enigmatic. Here, we report that AaORA forms a transcriptional activator complex with AaTCP14 (TEOSINTE BRANCHED 1/CYCLOIDEA/PROLIFERATING CELL FACTOR 14), which is also predominantly expressed in trichomes. AaORA and AaTCP14 synergistically bind to and activate the promoters of two genes, <i>double bond reductase 2</i> (<i>DBR2</i>) and <i>aldehyde dehydrogenase 1</i> (<i>ALDH1</i>), both of which encode enzymes vital for artemisinin biosynthesis. AaJAZ8, a repressor of the JA signaling pathway, interacts with both AaTCP14 and AaORA and represses the ability of the AaTCP14-AaORA complex to activate the <i>DBR2</i> promoter. JA treatment induces AaJAZ8 degradation, allowing the AaTCP14-AaORA complex to subsequently activate the expression of <i>DBR2</i>, which is essential for artemisinin biosynthesis. These data suggest that JA activation of the AaTCP14-AaORA complex regulates artemisinin biosynthesis. Together, our findings reveal a novel artemisinin biosynthetic pathway regulatory network and provide new insight into how specialized metabolism is modulated by the JA signaling pathway in plants.