Can we use tobacco to make a malaria drug?
Genetically modified tobacco plants can make large quantities of a molecule that is needed to make the drug artemisinin.
Malaria is by far the most devastating tropical disease in the world. It affects hundreds of millions of people — mainly in Africa and Asia — with almost half a million deaths every year. The most effective therapies against malaria all include the drug artemisinin, which is naturally found in an Asian plant called Artemisia annua. Unfortunately, the artemisinin content of A. annua plants is relatively low and the demand for this drug outstrips the supply of the plant. The costly production process makes artemisinin-based treatments inaccessible to many of the people in the most badly affected regions, and so researchers have been trying to find new ways to produce this drug.
Genetically modifying crop plants, such as tobacco, to produce artemisinin or related compounds could potentially provide a more sustainable and cheaper source of the drug. Inside plant cells, a structure called the nucleus contains DNA that encodes most of a plant’s genes, but compartments called mitochondria and chloroplasts also contain some DNA. Existing methods to genetically modify plants are able to insert a few genes into either the nucleus or the chloroplasts at a time. However, the production of artemisinin in A. annua involves many different genes that act at different stages of the process, and the precise roles played by many of them remain unclear.
Paulina Fuentes and colleagues developed a new approach to insert many of the A. annua genes involved in artemisinin production into tobacco plants at the same time, instead of one-by-one. The new method, referred to as COSTREL, takes advantage of the researchers’ ability to insert new genes into both the nucleus and the chloroplast of the tobacco plants. In the first step, Fuentes and colleagues inserted a core set of genes that are essential to make artemisinin into the chloroplast. This enabled the plants to produce a molecule called artemisinic acid, which the researchers can extract from the plants and convert into artemisinin by simple chemical reactions.
After testing different arrangements of the genes in the chloroplast, the plant line that had the highest levels of artemisinic acid was used to introduce a set of “accessory” genes into the nuclear DNA. These accessory genes are not strictly required to make the drug, but they help to regulate the process in a largely unknown manner. The experiments generated hundreds of genetically modified plant lines that each have different combinations of the accessory genes. Fuentes and colleagues examined these lines and were able to identify plants that could produce large amounts of artemisinic acid. Therefore, these findings lay the foundations for a cheap way to produce this life-saving drug in tobacco. In the future, the COSTREL method developed by Fuentes and colleagues could also be used to genetically engineer other complex biochemical processes into plants.
To find out more
Read the eLife research paper on which this story is based: “A new synthetic biology approach allows transfer of an entire metabolic pathway from a medicinal plant to a biomass crop” (June 14, 2016).
Listen to Ralph Bock talk about using plants as drug factories in this episode of the eLife podcast.
