# Dynamic Transcriptomics Reveals Coordinated Transcriptional Regulation of Artemisinin and Phenylpropanoid Biosynthesis Pathways in *Artemisia annua* Under Cold Stress
## Introduction
*Artemisia annua*, commonly known as sweet wormwood, is a medicinal plant renowned for its production of artemisinin, a sesquiterpene lactone that serves as the cornerstone of artemisinin-based combination therapies (ACTs) for malaria treatment. In addition to artemisinin, *A. annua* produces a variety of phenylpropanoids, which are secondary metabolites with antioxidant, antimicrobial, and stress-protective properties. Both artemisinin and phenylpropanoids are synthesized through complex biosynthetic pathways that are tightly regulated by environmental cues, including abiotic stresses such as cold.
Cold stress is a significant environmental factor that affects plant growth and metabolism. Plants respond to cold stress by reprogramming their transcriptomes to activate stress-responsive pathways and secondary metabolite biosynthesis. Recent advances in transcriptomics have enabled researchers to investigate the dynamic changes in gene expression under cold stress, providing insights into the coordinated regulation of metabolic pathways. In this article, we explore how dynamic transcriptomics reveals the interplay between the artemisinin and phenylpropanoid biosynthesis pathways in *A. annua* under cold stress, shedding light on the molecular mechanisms underlying stress adaptation and secondary metabolite production.
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## Artemisinin Biosynthesis Pathway
Artemisinin biosynthesis in *A. annua* involves the mevalonate (MVA) and methylerythritol phosphate (MEP) pathways, which provide the precursors for sesquiterpene lactone synthesis. The key steps in artemisinin biosynthesis include the conversion of farnesyl diphosphate (FPP) to amorpha-4,11-diene by amorpha-4,11-diene synthase (ADS), followed by a series of oxidation and cyclization reactions catalyzed by cytochrome P450 monooxygenases (CYP71AV1) and other enzymes.
Cold stress has been shown to influence the expression of genes involved in the MVA and MEP pathways, as well as downstream enzymes in the artemisinin biosynthesis pathway. Dynamic transcriptomic studies have revealed that cold stress induces the upregulation of ADS and CYP71AV1, suggesting that artemisinin biosynthesis is enhanced as part of the plant’s adaptive response to low temperatures. This upregulation may be mediated by transcription factors such as WRKYs, bHLHs, and AP2/ERFs, which are known to regulate secondary metabolism under stress conditions.
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## Phenylpropanoid Biosynthesis Pathway
The phenylpropanoid pathway is a central metabolic route in plants that produces a wide range of compounds, including flavonoids, lignins, and phenolic acids. These compounds play critical roles in plant defense, UV protection, and stress