The natural world has provided a cornucopia of pharmaceutical phenomena. From the earliest moments in recorded history, plants and herbs have provided relief to those suffering from a range of symptoms. Even today modern Pharma-giants rely heavily on the natural products of ancient remedies. Many drugs based on natural products are difficult to synthesise; for those which can be produced in the laboratory, chemical modification is usually necessary to cater to human consumption ( ie. adjusting potency, lessening side effects…). Aspirin and Anti-malarial drugs offer an excellent frame to understand the complexity of producing medicines from their virgin counterparts- many of which were used in ancient medical practice.
Willow bark was chewed as a remedy for a variety of ailments due to its anti-inflammatory properties in tradition Chinese practice. The active ingredient in the bark, Sacilin, when exposed to the digestive process is converted into Salicylic acid- the compound which provides the anti-inflammatory response ( see figure 1 ). However, Salicylic acid produces negative side effects such as gastric discomfort. Therefore when translating this remedy into a modern drug chemists had to produce a compound which would minimise the side effects whilst retaining potency of the natural product. Chemists synthesised a derivative of the compound via the esterification of Salicylic acid- acetyl salicylic acid, which is now found in Aspirin. Acetyl salicylic acid isn’t produced using Willow-bark and instead is synthetically produce: it is a simple molecule to make, less problems can arise when the production of the drug doesn’t rely on growing willow bark thereby ensuring reliable commercial availability.
Unlike Aspirin, the active compound of the drug advised by the WHO to treat malaria is more complex and cannot be as easily synthesised in the laboratory. Arterminsin is also present in traditional Chinese medicine and is derived from the Sweet Wormwood tree. The pure drug isolated from the tree isn’t particular soluble and has a short biological half life which required changes to improve.Cinchona alkaloids are alternative treatments however resistance against them has developed in single celled parasites that cause malaria thereby reducing their long term effectiveness. Therefore increasing the yield and the rate of production of Arterminsin important to make it commercially viable so treatment can be provided to those who need it. To successfully bioengineer a mechanism to produce Arteminsin requires an understanding of synthesis ( see figure 2 ) of the compound in plants and the enzyme controlled reactions which coordinate it. Then translating those mechanisms into the biochemical processes of the microorganism of choice- in this case yeast- to produce the drug in greater quantity.
Developments in chemical and biochemical engineering have allowed us to harness and mimic the complex machinery of the biochemical natural world to provide life saving treatment for many people around the world. The ancient process of harnessing natural phenomena for human use surely acts as testament to the ingenuity of the human race.
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