Complete biosynthesis of opioids in yeast
#MMPMID26272907
Galanie S
; Thodey K
; Trenchard IJ
; Filsinger Interrante M
; Smolke CD
Science
2015[Sep]; 349
(6252
): 1095-100
PMID26272907
show ga
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.
free
free
free
