Synthetic biology news: Opioids from yeast

I’d like to dedicate a bit of this blog to keeping up with some of the latest synthetic biology news. Science moves so quickly it helps to pause momentarily and appreciate what researchers have accomplished and where those discoveries might take us.

Just last week, scientists from Stanford published the first paper describing how they were able to engineer yeast to produce an opioid painkiller. It isn’t the first time that researchers hijacked these little cellular factories to do their bidding, but it was one of the most complex, and perhaps controversial, feats of engineering to date.

Opioids are a class of common painkillers; they are the active ingredients in medicines like Vicodin or Tylenol with codeine that bring relief to millions. At the same time, an estimated 36 million people around the world are addicted to opioids found in prescription drugs and heroin. Until now, all opioids have been derived from chemicals that occur naturally in poppy plants. Chemists have developed numerous strategies to synthesize the drugs in a test tube, but they are not feasible at the scale that medicine and science demand.

So a number of labs around the world have been working to exploit yeast to produce the drugs. Over the last few years, they have teased out various steps in the biosynthetic pathway, but a few steps remained elusive. Now, in work published in the latest issue of Science, Christina Smolke describes how her lab was able to complete the synthesis.

It wasn’t simply a matter of putting genes from a poppy plant into yeast. The synthesis of thebaine, an opiate precursor of morphine, required yeast to express 21 genes from plants, bacteria, and rats – 7 species in all! Hydrocodone production required 23 genes. Even then, the process wasn’t easy. Smolke and her team found that one gene, SalSyn, was improperly glycosylated so they did a bit of protein engineering and made a chimera, borrowing nonglycosylated sequences from a closely related protein.

The results are more of a proof-of-principle rather than a protocol that companies – or illegal drug cartels – could use to make reasonable amounts of opioids. The yeast weren’t very efficient in producing either chemical. In fact, Smolke estimates that it would take more than 4000 liters of yeast to produce the amount of hydrocodone found in a single Vicodin pill.

There are obvious social concerns with this type of work, and these scientists appear to be working hard to ensure that their research does not feed addiction. But beyond those concerns, I’m excited about the promise this research holds. It is possible that in the not too distant future, synthetic biology may be the key to modified and improved opioids that are less addictive and more potent. And the utility of engineered yeast is likely to extend way beyond opioids. I’m confident that scientists will be able to turn yeast cells into nano-factories capable of producing other small molecules that have been difficult to synthesize chemically. More and more drugs will be quickly and efficiently synthesized in yeast – stay tuned.

640px-Poppy_field_(19635794351)

Photo: “Poppy field (19635794351)” by Susanne Nilsson – Poppy field. Licensed under CC BY-SA 2.0 via Wikimedia Commons – https://commons.wikimedia.org/wiki/File:Poppy_field_(19635794351).jpg#/media/File:Poppy_field_(19635794351).jpg

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