Wednesday, August 26, 2015

Producing opiates from sugar

For several years, synthetic research teams have modified pathways into microorganisms to produce benzylisoquinoline alkaloids which are used in pharmacology. If it were possible, the analgesic production would be cheaper, safer and more effective. In recent years, synthetic biologists have engineered yeast strains to make morphine (belonging to opiates, naturally produced from the opium poppy Papaver somniferum) from sugar.
Going from glucose to morphine is a complex pathway which is carried out in 18 stages. Vicent Martin and his collages at Concordia University in Montreal, Canada, created yeast that can go to R-reticuline to morphine. R-reticuline is an intermediate compound in this pathway. To go from glucose to S-reticuline (an intermediate compound before R-reticuline), John Deuber's team at University of California, Berkeley carried out their research. Both groups worked together to found the enzyme needed to transform S-reticuline to R-reticuline and have the complete pathway, but this could take many years. 

Stages known of glucose-morphine pathway. (Oye et al., 2015)

The last week, a research team by Cristina Smolkey, a synthetic biologist at Standford Universty in Palo Alto, California, published in Science that they had achieved to turn sugar into thebaine, a key opiate precursor to morphine, by a Saccharomyces cerevisiae strain. This biosynthesis required the expression of 21 genes from a rat, a bacterium and several plants. This research presents the most complete pathway of glucose to morphine, because thebaine is the last intermediate in this pathway, but is still the first piece of the project. Is necessary to increase the yield to each cell 100, 000 times to accomplish that the process scales up, be economically feasible and can compete with the oppium poppy production in pharmacology.


- Galanie, S., Thodey, K., Trenchard, I. J., Interrante, M. F., & Smolke, C. D. (2015). Complete biosynthesis of opioids in yeast. Science, aac9373.

- Oye, K. A., Lawson, J. C., & Bubela, T. (2015). Drugs: Regulate'home-brew'opiates. Nature,521(7552), 281.

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