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Natural Products


Sweet wormwood (Artemisia annua or Qinghao in Chinese), is an annual herb of the Asteraceae family. Artemisinin derived from the sweet wormwood plant has anti- malaria effects and has saved millions of lives. Photo by Kristian Peters


protein-coding genes – one of the largest num- bers among all sequenced plant species. The researchers found that multiple enzymatic


steps are involved in artemisinin biosynthesis, implying that there may be more than one enzy- matic step limiting the metabolic flux into artemisinin biosynthesis. With this in mind, the team generated transgenic


A. annua lines. By simultaneously overexpressing multiple genes functioning in the upstream (HMGR), midstream (FPS) and downstream (DBR2) of the artemisinin biosynthetic pathway, they were able to produce high artemisinin levels that were 51%-103% higher than wild-type plants.


Where none have gone before Among the 900 species of the medicinally impor- tant Rutaceae family is the winged prickly ash (Zanthoxylum planispinum), which produces a wide variety of phytochemicals, including alka- loids, amides, lignans, essential oils and fatty acids. Widely used as a medicinal herb for the treat-


ment of colds, stomach aches, snakebites, toothaches and roundworm, Z. planispinum may also have anticancer, antiviral, antimicrobial, antiplatelet aggregation, antioxidant and anti- inflammatory activities, making it a focus of many


Drug Discovery World Spring 2019


pharmacology studies. However, molecular biolo- gy studies of this plant are rare, with no compre- hensive genomic and transcriptomic data available in the NCBI plant database. To rectify this, a team of Korean researchers, led


by Ik-Young Choi of Kangwon National University, turned to whole transcriptome sequenc- ing to obtain gene function data and elucidate the complex mechanisms involved in regulating gene expression. As reported in July 20184, the scientists analysed


full-length cDNA sequences using the Iso-Seq method, obtaining 51,402 uniquely-assembled transcripts (‘unigenes’) from the tissues of leaf, early fruit and maturing fruit of Z. planispinum. Among their targets of particular interest were


cytochrome P450 monooxygenases (CYP450s), which comprise a large and complex superfamily whose members are found in almost all living organisms. Plant P450s are involved in various pathways, such as the synthesis of UV protectants (flavonoids and anthocyanins); defence com- pounds (isoflavonoids, hydroxamic acids and ter- penes); and signalling molecules (salicylic acid and jasmonic acid). Targeting plant P450s via metabol- ic engineering would be valuable for the large-scale production of their phytochemicals as medicine, but these enzymes are present in very low quanti-


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