Stanford researchers convert yeast into painkillers

It typically takes a full year to convert plants into hydrocodone, but researchers from Stanford University have developed a new technique involving baker’s yeast that allow them to transform sugar into painkillers in just three to five days, according to published reports.

Their method, described in a recent edition of the journal Science, could open the door for these opioids, as well as chemical relatives such as morphine and oxycodone, to be created faster and at a lower cost than many other types of plant-based medicines, the authors said.

As part of their research, Stanford bioengineer Christina Smolke and her colleagues successfully found more than 20 genes from five different organisms and inserted them into the genome of baker’s yeast. By doing so, they managed to create a pair of microbial assembly lines which they used to convert sugar into one of two medicinal compounds: thebaine or hydrocodone.

The process currently requires 4,400 gallons of bioengineered yeast to produce just one dose of the painkillers, but the study shows that complex plant-based medications can be made with the help of genetically altered microorganisms – and the authors say this is just the beginning.

As Smolke said in a statement, “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.”

Building on techniques used to create anti-malarial drugs

Experiments conducted prior to the Stanford team’s work demonstrated that genetically altered yeast could be used to produce the anti-malarial drug artemisinin. In that experiment, however, the researchers only added six genes to produce the desired result. The authors of the new paper needed to engineer 23 genes into the yeast genome to produce their hydrocodone assembly line.

“This is the most complicated chemical synthesis ever engineered in yeast,” Smolke said. She and her colleagues were able to locate and fine-tune DNA fragments from other plants, bacteria, and even rodents that they then equipped to the yeast. This gave it all of the enzymes required to change sugar to hydrocodone, a compound which deactivates pain receptors in the brain.

However, in order to get this yeast-based assembly line up and running, the researchers needed to find a way to replicate or replace the process through which opium poppies naturally convert the (S)-reticuline molecule into the (R)-reticuline molecule, which is what kick-starts the plant’s journey towards the production of pain-relieving molecules.

Smolke’s team was one of three labs which independently discovered the enzyme that causes (S)-reticuline to become (R)-reticuline, but even this did not create enough opioid compound, so they altered the next enzyme in this process in order to increase production levels. New enzymes were continually added down the line, the researchers explained, until they ultimately managed to create a molecule that could be plugged directly into the brain’s pain receptors.

“Biotech production could lower costs and, with proper controls against abuse, allow bioreactors to be located where they are needed,” said Smolke. “The molecules we produced and the techniques we developed show that it is possible to make important medicines from scratch using only yeast. If responsibly developed, we can make and fairly provide medicines to all who need.”


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