By David Niesel and Norbert Herzog
Affectionately called molecular biology on steroids, synthetic biology in its simplest sense is deliberately modifying simple organisms to make medicines or other molecules that have commercial value. Through these advances we are beginning to harvest a treasure trove of discoveries in medicine.
Many of our medicines are compounds that were originally derived from plants or other living organisms, made in cells from simple molecules like sugar and nitrogen. For example, aspirin is made in the bark of willow trees through a series of steps called a biochemical pathway. Today we do not produce aspirin by extracting it from willow bark because it is cheaper and more efficient to synthesize it chemically. It would be great if we could produce all our medicines this way, but unfortunately some compounds cannot be easily or cheaply synthesized.
This is where synthetic biology comes to the rescue, with some assistance from Saccharomyces cerevesiae — which you probably know as yeast, the same kind used to make bread and beer. We know a lot about the physiology and genetics of yeast, mostly because it was the first eukaryote, or organism with cells like ours, to have its genome sequenced. This knowledge makes it easy to exploit these cells for synthetic biology.
We can move all or most of the genes for any biochemical pathway into a yeast cell. It can now reproduce the series of chemical steps to make the active molecule needed for drug production. The advantage of using yeast to produce drugs is that we can grow billions of these engineered organisms in the lab, optimize the production of the compound, and then extract it. No growing or harvesting of plants, complicated extractions or extensive chemical synthesis necessary.
There have been several drugs successfully produced using engineered yeast. We have previously written about yeast production of artemisinic acid, a precursor of artemisinin, the most effective drug for malaria. A recent report has described the production of morphine and other alkaloids, which were originally derived from the poppy plant, via synthetic biology and yeast. Until the genome of the poppy was determined in 2010, we did not know all the genes needed to make morphine in a cell. But now, that knowledge combined with engineered yeast can produce morphine and the many pain relievers made from it inexpensively. This would produce a reliable supply without the political, criminal and environmental issues that come from cultivating poppy naturally. Since heroin is created from morphine by a simple chemical modification, this could have a big impact on the illicit drug trade.
Although this is all good news, additional steps will be needed to produce morphine directly from the simple sugars used to feed the yeast. Producing morphine synthetically will also need to be heavily controlled so that criminal organizations do not acquire the technology. Finally, legitimate farmers who produce morphine for drug use would likely be replaced by yeast factories. Overall, synthetic biology production of morphine would be bad news for poppy farmers but good news to those in pain.
Professors Norbert Herzog and David Niesel are bio-medical scientists at the University of Texas Medical Branch. Learn more at medicaldiscoverynews.com{/span}