It normally takes around a year to create painkillers from opium poppies, as first they have to be grown, harvested, shipped around the world and finally processed. This week, however, researchers have been able to cut this time down to just a few days, by genetically engineering yeast to do it instead. What normally happens is that by processing the poppies, scientists get the chemical thebaine, which they then turn into the opioid hydrocodone, a widely used painkiller. The team, from Stanford, have engineered the yeast to produce hydrocodone from sugar.
“When we started work a decade ago, many experts thought it would be impossible to engineer yeast to replace the entire farm-to-factory process,” explained Christina Smolke, lead author of the study published in Science. “This is only the beginning. The techniques we developed and demonstrate for opioid pain relievers can be adapted to produce many plant-derived compounds to fight cancers, infectious diseases and chronic conditions such as high blood pressure and arthritis.”
The researchers were able to tweak the genetic machinery of the yeast, inserting 23 genes taken from a wide range of species, including plants, bacteria, and even rats. This is one of the most complex chemical pathways ever created in yeast. It goes to prove how powerful synthetic biology – editing biological organisms for our benefit – can be in making microbes produce complicated substances of use to us.
Building on previous research using yeast to produce the antimalarial drug artemisinin, the researchers were finally able to bridge a gap in the production of opioids. The developments in this production have progressed surprisingly rapidly, with breakthroughs in replicating sections of the process coming through thick and fast in the last year or so. It got to the point where scientists were able to get yeast to demonstrate the first and second half of the pathway to produce opioids, but required an enzyme to link the two.
According to Smolke, her team had largely managed to replicate the entire process by May this year, years earlier than anyone could have predicted. There is, however, still a long way to go. Proof of concept has been shown, but the production still needs refinement, as it currently takes around 20,000 liters (4,400 gallons) of bioengineered yeast to produce a single dose of hydrocodone.
One of the main issues here is the risk of making it easier to create illicit substances, such as heroin, in the same way people brew beer. In fact, Smolke and her team specifically stopped short of creating the complete morphine pathway because of these concerns. “We want there to be an open deliberative process to bring researchers and policymakers together,” explained Smolke. “We need options to help ensure that the bio-based production of medicinal compounds is developed in the most responsible way.”