Nadine E. Hilman
Collaboration continues to have a steadfast role in the evolving fields of STEM. The emerging area of synthetic biology, where engineers and biologists converge, is perhaps the paragon of multidisciplinary collaboration in this day and age. Synthetic biology aims to “re-engineer genetic engineering”, by artificially designing biological systems that may serve to benefit environmental and medical purposes. To paint a clearer picture, synthetic biology is concerned with creating DNA and other biological parts; redesigning existing microbes to enhance their natural functions, and ultimately pioneering the field of genetic engineering. In this article, one particular breakthrough in the field of synthetic biology will be explored -- namely the engineering of a metabolic pathway in yeast to produce the precursor for an anti-malarial drug.
Malaria is a fatal disease caused by various strains of the Plasmodium parasite. It kills “more than one million people annually”, and disproportionately affects low-income communities, primarily due to poor health intervention and expensive health treatments (WHO). Artemisinin, a drug derived from sweet wormwood, has proven to be an effective anti-malarial drug, however its low bioavailability, as well as the costly resources needed to synthesize it, cause the drug to be unaffordable. Due to this pressing situation, in 2006, a team of synthetic biologists over at UC Berkeley managed to genetically engineer a species of yeast, Saccharomyces cerevisiae, to produce artemisinic acid, the precursor of artemisinin. This cost-effective procedure could potentially lead to an on-demand and inexpensive anti-malarial drug to alleviate the economic burden of low SES households suffering from malaria. As you can see, outside of this ’Jurassic World’, test tube baby’ and ultimately futuristic portrayal of gene editing, genetic engineering (and synthetic biology) can be weaponized to serve today’s urgent issues too.
So how did these scientists make it happen? In the A. annua plant from which artemisinin is usually extracted from, the mevalonate pathway is used to produce isoprenoid compounds, which are precursors of artemisinin. To address the inefficient and costly process of extracting artemisinin from plants, scientists have engineered a transgenic Saccharomyces cerevisiae, more commonly known as baker’s yeast, to express enzymes derived from A.annua i.e amorphadiene synthase and CYP71AV1 (Ro et al.). Amorphadiene synthase leads to the production of amorphadiene , while CYP71AV1, a cytochrome P450 enzyme, facilitates the oxidation of amorphadiene to artemisinic acid. Essentially, the expression of these enzymes allowed for the reconstruction of the mevalonate pathway present in yeast, resulting in the production of artemisinic acid, one of the final precursors of artemisinin. Once the artemisinic acid is isolated from yeast, organic chemistry is then used to purify and convert the compound into artemisinin (Kayani et al.). This semi-synthetic route was approved by the WHO in 2013, and is slowly beginning to enter the market.
Overall, the semi-synthesis of artemisinin to attenuate the epidemic of malaria in developing countries proves the power of science and technology as a catalyst of social change. This brilliant field also reflects the wonders that can be achieved when there is a collaboration between disciplines -- in the same way that no man is an island, no sector should be one either. As the scientific community continues to work towards optimizing antibiotics, natural products, and biofuels, it is clear that synthetic biology will have a central role in our near future.
Note: Check out the abstract over at https://pubmed.ncbi.nlm.nih.gov/16612385/ to read more!
Bibliography
Kayani, Waqas Khan et al. "Biotechnological Approaches For Artemisinin Production In Artemisia". World Journal Of Microbiology And Biotechnology, vol 34, no. 4, 2018. Springer Science And Business Media LLC, doi:10.1007/s11274-018-2432-9. Accessed 30 June 2020.
Ro, Dae-Kyun et al. "Production Of The Antimalarial Drug Precursor Artemisinic Acid In Engineered Yeast". Nature, vol 440, no. 7086, 2006, pp. 940-943. Springer Science And Business Media LLC, doi:10.1038/nature04640. Accessed 30 June 2020.
WHO. "WHO | World Malaria Report 2005". Who.Int, 2020, https://www.who.int/malaria/publications/atoz/9241593199/en/.
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