Opioid compounds synthesized from yeast

August 13, 2015

Following progress in identifying all components in the opioid production pathway, researchers have manipulated yeast to synthesize thebaine, a poppy opiate that is a precursor to many medically relevant opioids. The only current source of opioids, the most powerful medical substances available for treating pain, is the opium poppy, Papaver somniferum, making production reliant on poppy farming. A microbial-based production process could significantly reduce the production period of opioid compounds. Yeast has been engineered to produce a variety of plant-based natural products, but reconstructing the complex pathways to opioids and their precursors has been a challenge. To produce the precursor thebaine, Stephanie Galanie et al. engineered yeast with the enzymes required for the synthetic steps, starting with sugar as the fuel source. Additional engineering was required to ensure efficient flux through the pathway. The pathway in the resulting yeast strain expressed 21 enzymes from plants, mammals, bacteria and yeast. The pathway was extended to express two additional enzymes to achieve production of hydrocodone, a common semi-synthetic opioid drug. While this study highlights the novel production of opioid substances through a microbial-based method, the current yield is miniscule; it ultimately could create a new source of pain relief and improved palliative care for those suffering from pain, worldwide, but much additional work is required for this process to translate into practical commercial applications.
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Article #20: "Complete biosynthesis of opioids in yeast," by S. Galanie; K. Thodey; I.J. Trenchard; M.F. Interrante; C.D. Smolke at Stanford University in Stanford, CA.

American Association for the Advancement of Science

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