Complete biosynthesis of opioids in yeast

Significance Statement

Stanford University research team led by Dr. Smolke engineered yeast to produce hydrocodone.  The development process involved genetically modifying 23 enzymes.  Genetically modified Yeast cells were enabled to produce hydrocodone within 3-5 days. This technology may make opoids production for pain management more affordable to under developed countries.

Complete biosynthesis of opioids in yeast. Global Medical Discovery






Journal Reference

Stephanie Galanie1Kate Thodey2Isis J. Trenchard2Maria Filsinger Interrante2Christina D. Smolke2

Science DOI: 10.1126/science.aac9373. Published Online August 13 2015

1Department of Chemistry, Stanford University, Stanford, CA 94305, USA.

2Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.


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. Here, 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 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.

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