Complete biosynthesis of opioids in yeast
By Stephanie Galanie, Kate Thodey, Isis J Trenchard, Maria V. Filsinger Interrante, Christina D. Smolke. Science, 2015
878 citations recorded by the source corpus.
Toward opioids without poppy fields Producing opioids without having to depend on field-grown poppies would be of great benefit. Synthetic production could potentially produce more-effective drugs with fewer side effects. Now, Galanie et al. have engineered yeast to produce the opioid compounds thebaine and hydrocodone, starting from sugar (see the Perspective by Nielsen). The amounts produced so far are tiny compared with what would be needed commercially. Future optimization and scaleup are the next challenge. Science, this issue p. 1095; see also p. 1050 The pathway for synthesizing two opioids from sugar has been engineered into yeast. [Also see Perspective by Nielsen] Opioids are the primary drugs used in Western medicine for pain management and palliative care. Farming of opium poppies remains the sole source of these essential medicines, despite diverse market demands and uncertainty in crop yields due to weather, climate change, and pests. We engineered yeast to produce the selected opioid compounds thebaine and hydrocodone starting from sugar. All work was conducted in a laboratory that is permitted and secured for work with controlled substances. We combined enzyme discovery, enzyme engineering, and pathway and strain optimization to realize full opiate biosynthesis in yeast. The resulting opioid biosynthesis strains required the expression of 21 (thebaine) and 23 (hydrocodone) enzyme activities from plants, mammals, bacteria, and yeast itself. This is a proof of principle, and major hurdles remain before optimization and scale-up could be achieved. Open discussions of options for governing this technology are also needed in order to responsibly realize alternative supplies for these medically relevant compounds.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/2fcd4d00e67b30918214d43feb30b398a5632154
Citations in the corpus
- Engineering Cellular Metabolism (2008, neutral): “…heterologous expression requires enzyme discovery as part of 1186 Cell 164, March 10, 2016 ª2016 Elsevier Inc. the metabolic engineering program, as illustrated for production of artemisinic acid (Ro et al., 2006; Westfall et al., 2012; Paddon et al., 2013) and opioids (Galanie et al., 2015).”