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Complete absence of thebaine biosynthesis under home-brew fermentation conditions

Drew Endy, Stephanie Galanie, Christina D. Smolke
doi: https://doi.org/10.1101/024299
Drew Endy
^Department of Bioengineering; 443 Via Ortega, MC 4245 Stanford University; Stanford, CA 94305
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Stephanie Galanie
#Department of Chemistry; 443 Via Ortega, MC 4245 Stanford University; Stanford, CA 94305
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Christina D. Smolke
^Department of Bioengineering; 443 Via Ortega, MC 4245 Stanford University; Stanford, CA 94305
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  • For correspondence: csmolke@stanford.edu
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Abstract

Yeast-based biosynthesis of medicinal compounds traditionally derived from plant materials is improving. Both concerns and hopes exist for the possibility that individual small volume batch fermentations could provide distributed and independent access to a diversity of compounds some of which are now abused, illegal, or unavailable to many who need for genuine medical purposes. However, there are differences between industrial bioreactors and ‘home-brew’ fermentation. We used engineered yeast that make thebaine, a morphinan opiate, to quantify if differences in fermentation conditions impact biosynthesis yields. We used yeast that make an English ale as a positive fermentation control. We observed no production of thebaine and miniscule amounts of reticuline, an upstream biosynthetic intermediate, in home-brew fermentations; the positive control was palatable. We suggest that additional technical challenges, some of which are unknown and likely unrelated to optimized production in large-volume bioreactors, would need to be addressed for engineered yeast to ever realize home-brew biosynthesis of medicinal opiates at meaningful yields.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted August 13, 2015.
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Complete absence of thebaine biosynthesis under home-brew fermentation conditions
Drew Endy, Stephanie Galanie, Christina D. Smolke
bioRxiv 024299; doi: https://doi.org/10.1101/024299
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Complete absence of thebaine biosynthesis under home-brew fermentation conditions
Drew Endy, Stephanie Galanie, Christina D. Smolke
bioRxiv 024299; doi: https://doi.org/10.1101/024299

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