Publication Date:
2015-08-15
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Galanie, Stephanie -- Thodey, Kate -- Trenchard, Isis J -- Filsinger Interrante, Maria -- Smolke, Christina D -- 1S10RR02557401/RR/NCRR NIH HHS/ -- AT007886/AT/NCCIH NIH HHS/ -- New York, N.Y. -- Science. 2015 Sep 4;349(6252):1095-100. doi: 10.1126/science.aac9373. Epub 2015 Aug 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Stanford University, Stanford, CA 94305, USA. ; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. ; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. csmolke@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26272907" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Benzylisoquinolines/metabolism
;
Biosynthetic Pathways/genetics
;
Carbohydrate Metabolism
;
Codeine/metabolism
;
Genetic Engineering/*methods
;
Hydrocodone/chemistry/*metabolism
;
Morphinans/chemistry/metabolism
;
Papaver/enzymology/genetics
;
Saccharomyces cerevisiae/*enzymology
;
Thebaine/chemistry/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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