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Metabolic engineering of plant medicines – Nature Reviews Genetics

For centuries, plants have provided a broad palette of molecules essential to human medicine for the treatment of various illnesses such as infectious diseases, neurodegenerative disorders and cancers. However, manufacturing these precious medicines has always been challenging. Indeed, plant-derived pharmaceutical drugs often display complex structures, precluding their chemical synthesis at industrial scales. In addition, these compounds accumulate naturally in minute amounts in the source plants, which explains their unsustainable and highly costly supply. The emergence of synthetic biology in the early 2000s opened up alternative routes to produce prominent plant-derived medicines. In 2006, Ro et al. published a seminal article in Nature reporting the biosynthesis of a complex plant natural product to treat malaria by an engineered microorganism.

Malaria kills hundreds of thousands of people each year. Treatment with the highly valuable molecule artemisinin and its derivatives has dramatically reduced this death toll, as acknowledged with the 2015 Nobel Prize in Physiology or Medicine awarded to Tu Youyou. However, the effect of such a treatment has been hampered by restricted access to the source plant, the annual wormwood Artemisia annua. Ro et al., with the Keasling laboratory, developed a game-changing approach by creating a yeast strain capable of synthesizing artemisinic acid, a precursor of the antimalarial drug.