Researchers from the Max Planck Institute of Molecular Plant Physiology in Potsdam have altered tobacco to produce large yields of artemisinin – the most effective treatment for malaria but still without a cheap and reliable source.

max_planck_costrel_tobacco_artemisininArtemisinin is used in the most effective treatments against malaria, the discovery of which was worth a Nobel Prize. However, it too expensive to be widely accessible. While malaria deaths fell by 60% worldwide in recent years (according to WHO), half of a million people still died with the disease in 2015.

Part of the problem is that artemisinin is extracted from a herb (Artemisia annua), which produces low yields and often has an erratic supply.

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artemisia_annua_artemisinic_acid_gmo_tobacco

Artemisia annua plant (CC 3.0 Kristian Peters), which produces artemisinic acid (a precursor to artemisinin).

To tackle this problem, researchers from the Max Planck Institute for Molecular Plant Physiology looked into plant synthetic biology.

In a work published in eLifethe researchers developed a method to produce artemisinin with tobacco – a popular plant in biotechnology, since it is a source of biomass (for Deinove’s biofuels, for example) and recombinant proteins (it was used to produce antibodies for ebola).

The researchers inserted several genes in the chloroplasts‘ genome (a trend in genetically modified plants). These genes code for all the proteins involved in the metabolic pathway to produce artemisinic acid in A. annua. This method of inserting all genes at the same time was named COSTREL.

After selecting the most productive plants from hundreds of variants (with different gene arrangements and accessory genes), the researchers had a tobacco plant that expressed promising quantities artemisinic acid in its leaves.

Fig. 1: Metabolic pathway of artemisinic acid.

Fig. 1: Metabolic pathway of artemisinic acid.

This is not the first time that SynBio tries to make artemisinin’s supply cheaper and more reliable. The engineering of the pathway for artemisinic acid in yeast was a major milestone in the field. It was licensed to Sanofi to produce malaria therapies. However, it turned out to be more expensive than traditional sources, and Sanofi is now selling its artemisinin plant.

Production in tobacco could be cheaper and better answer the dynamics of the drug’s price, as it doesn’t require expensive raw materials or large bioreactors run under GMP conditions.

Even if the current application in artemisinin is a solution to a disappearing problem, this early success in the new COSTREL method could pave the way to engineer other complex biochemical processes into plants.


Feature Image Credit: Tobacco plants (CC 2.0 Wisconsin Department of Natural Resources)
Figure 1 Credit: Fuentes et al. (2016) A new synthetic biology approach allows transfer of an entire metabolic pathway from a medicinal plant to a biomass crop. eLife (doi: 10.7554/eLife.13664)

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