Not the only way to produce opiates (Image: Simon DESCAMPS/getty)

Severe pain? Reach for the yeast. Genetically engineered yeasts can now efficiently produce a range of opiates, including morphine and oxycodone. With growing anxieties about supplies of opium poppies, it could be just what the doctor ordered.

Opiates are primarily used as painkillers and cough suppressants, and many of the most widely used opiates can be produced only from opium poppies (Papaver somniferum). Demand for these drugs is booming. But of the poppies farmed to supply these drugs, some 50 per cent are grown on the Australian island of Tasmania, so poor growing seasons can affect availability.

As drug companies search for new places to grow poppies, Christina Smolke from Stanford University, California, and her colleagues have been looking at getting yeast to make these complex drugs from simple sugars.


Some opiates, like morphine, are made naturally by poppies. Others, like oxycodone, are produced by chemically altering one of the plant’s natural alkaloid chemicals – in this case thebaine. Back in 2008, Smolke inserted a number of genes – including some from the opium poppy – into yeasts, and got them to turn simple sugar molecules into a complex precursor of opiates: salutaridine. Now, in her latest work, she has solved the other end of the pathway, engineering yeasts to take complex precursors like thebaine and synthesise the finished products, including oxycodone.

“This work gets us very close,” says Smolke. All that’s left is to combine the two stages in one strain of yeast, and solve the last few steps: getting the yeast to turn salutaridine into thebaine, completing the pathway from sugar to opiate product.

Secure supply

The benefits of yeast over poppies are manifold, Smolke says. She thinks that when the system is finished, a 1000-litre tank could produce as much morphine as a hectare of poppies. She believes the method, when completed, will also increase security. “It is difficult or impossible to secure many thousands of acres of poppy fields which are grown out in the open,” she says. “Yeast will be grown in closed fermenters and can be kept in secure facilities.”

But yeast-made opiates may struggle to usurp opium poppies. Tim Bowser, head of opiate research and development at GlaxoSmithKline, says that the same understanding of opiates that is making this yeast technology possible is also helping to make opiate production more efficient in poppies. The yeast method will have to be highly efficient and low-cost before it could replace the plants, he says.

Although the competition with natural opium is likely to be tough, the yeast method could also open up new possibilities. By tweaking the yeast’s food, as well as the genes it expresses, Smolke says the technique could be used to produce new, and possibly better, opiates. Security could be boosted further by engineering the yeasts to require very particular growing conditions, and genetic barcoding could be used to trace illegal sources.

Journal reference: Nature Chemical Biology, DOI: 10.1038/nchembio.1613