Genetically-modified yeast yields powerful painkillers

In a breakthrough, Stanford scientists have genetically engineered baker's yeast to develop powerful but cheap narcotic painkillers.
The technique can also be adapted to produce many cheap plant-derived compounds to fight cancers, infectious diseases and chronic conditions such as high blood pressure and arthritis, researchers said.
The researchers reprogrammed the genetic machinery of baker's yeast so that these fast-growing cells could convert sugar into hydrocodone in just three to five days.
Hydrocodone and its chemical relatives such as morphine and oxycodone are opioids, members of a family of painkilling drugs sourced from the opium poppy.
It can take more than a year to produce a batch of medicine. Plant material must then be harvested, processed and shipped to pharmaceutical factories, where the active drug molecules are extracted and refined into medicines.

Now, though the output is small - it would take 4,400 gallons of bioengineered yeast to produce a single dose of pain relief - the experiment proves that bioengineered yeast can make complex plant-based medicines.

"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," said senior author Christina Smolke, an associate professor of bioengineering at Stanford University.
Many medicines are derived from plants, which our ancestors chewed or brewed into teas.
Smolke's team is modernising the process by inserting precisely engineered snippets of DNA into cells, such as yeast, to reprogramme the cells into custom chemical assembly lines to produce medicinal compounds.

The team had to engineer 23 genes into yeast to create their cellular assembly line for hydrocodone.
Her team found and fine-tuned snippets of DNA from other plants, bacteria and even rats that equipped the yeast to produce all the enzymes necessary for the cells to convert sugar into hydrocodone, a compound that deactivates pain receptors in the brain.
Many plants, including opium poppies, produce (S)-reticuline, a molecule that is a precursor to active ingredients with medicinal properties.
In the opium poppy, (S)-reticuline is naturally reconfigured into a variant called (R)-reticuline, a molecule that starts the plant down a path towards the production of molecules that can relieve pain.

Smolke's team and two other labs recently independently discovered which enzyme reconfigures reticuline, but even after the Stanford bioengineers added this enzyme into their microbial factory, the yeast didn't create enough of the opioid compound.
So they genetically tweaked the next enzyme in the process to boost production.
The study was published in the journal Science.