Parallel Transcriptional Regulation of Artemisinin and Flavonoid Biosynthesis

Plants regulate the synthesis of specialized compounds through the actions of individual transcription factors (TFs) or sets of TFs. One such compound, artemisinin from Artemisia annua, is widely used as a pharmacological product in the first-line treatment of malaria. However, the emergence of resistance to artemisinin in Plasmodium species, as well as its low production rates, have required innovative treatments such as exploiting the synergistic effects of flavonoids with artemisinin. We overview current knowledge about flavonoid and artemisinin transcriptional regulation in A. annua, and review the dual action of TFs and structural genes that can regulate both pathways simultaneously. Understanding the concerted action of these TFs and their associated structural genes can guide the development of strategies to further improve flavonoid and artemisinin production. It is increasingly recognized that different TFs act conjointly to regulate the production of plant metabolites. However, their dual functionality in regulating distinct pathways of synthesis has not been well studied.The identification of cis-regulatory elements within the promoter regions of genes encoding different pathway enzymes enables the identification of TF families that regulate their expression.Parallel regulation of the enzyme-coding genes for distinct pathways can simplify overexpression strategies.This provides an excellent starting point to unravel how individual TFs act in a coordinated manner to simultaneously regulate different pathways of specialized metabolism.