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Stanford bioengineers close to brewing opioid painkillers without using opium from poppies
Date:8/24/2014

s occur naturally in poppies and the remaining via synthetic chemical processes in factories. Smolke's team wanted all the steps to happen inside yeast cells within a single vat, including using yeast to carry out chemical processes that poppies never evolved to performsuch as refining opiates like thebaine into more valuable semi-synthetic opioids like oxycodone.

So Smolke programmed her bioengineered yeast to perform these final industrial steps as well. To do this she endowed the yeast with genes from a bacterium that feeds on dead poppy stalks. Since they wanted to produce several different opioids, the team hacked the yeast genome in slightly different ways to produce each of the slightly different opioid formulations, such as oxycodone or hydrocodone.

Subtitle: The Missing Link

All of this was demonstrated in the new paper. But Smolke's team must still clear one more hurdle in order to achieve the goal of pouring sugar into a stainless steel vat of bioengineered yeast and skimming off specific opioids at the end of the process. They must perform another set of bioengineering hacks to connect the two major advances they have made over the past decade.

Remember that it takes about 17 chemical steps to go from poppy to pill. When she began the work in 2004, Smolke started early in the process and went about halfway through these chemical steps. In a 2008 paper she reported success in that first phase of the project when her bioengineered yeast produced a precursor to thebaine--one of the three principal opiates.

In her new paper, Smolke started with thebaine obtained from poppies, put this into her bioengineered yeast and got refined opioids at the end of the process.

Now her team must extend the 2008 process from sugar to thebaine. Once she forges this missing link in the chain of biochemical synthesis, she will have produced a bioengineered yeast that can perform all 17 steps from sugar to specific
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Contact: Tom Abate
tabate@stanford.edu
650-736-2245
Stanford School of Engineering
Source:Eurekalert  

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