Proof-of-principle study shows that engineered yeast can fully synthesize opioids from sugar
Is sugar the new source for opioids? A research group from Stanford University has reported in the journal Science that they have successfully engineered yeast strains to synthesize two opioids, hydrocodone and thebaine, from a simple sugar source. Thebaine is a common precursor for the opioids oxycodone, codeine, and hydrocodone, all of which are powerful drugs used by medical professionals to manage pain. At present, the opium poppy is the sole source of all opiates, and the poppy farming industry faces increasing challenges due to high market demand and variable crop yield.
The research group, led by bioengineer Dr. Christina D. Smolke, was able to produce total opiate biosynthesis by reconstructing major steps of the opioid manufacturing pathway in yeast. Additional enzymatic genes were incorporated from a wide variety of genetically diverse organisms, and each step in the pathway was painstakingly verified for the generation of the correct precursor compound. In the end, the expression of 21 and 23 genes were required to fully synthesize thebaine and hydrocodone, respectively, from sugar.
The microbial-based synthesis of opioids is, however, far from producing a high enough yield for scale-up to commercial production. In fact, the authors estimate that a 100,000-fold improvement would be required to make their opioid-manufacturing process a viable alternative to the poppy.
Galanie S, Thodey K, Trenchard IJ, Filsinger Interrante M, Smolke CD. Complete biosynthesis of opioids in yeast. Science, August 13 2015. epub ahead of print.
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Written by Fiona Wong, PhD