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.

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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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Basic Tips to Prevent Bee Swarming

Dr. Jef Boeke presently serves New York University’s (NYU) Langone Medical Center as a professor and director in the Institute for Systems Genetics (ISG). Beyond his work at NYU, Dr. Jef Boeke enjoys beekeeping.

One of the first things every beginning beekeeper must learn is how to prevent bees from swarming. In the wild, swarming is a completely natural part of a bee’s life cycle. As a single colony grows in size, up to half of the hive may leave in unison to find a new home. This process is known as swarming. For bees in an apiary, swarming equates to lower-than-expected honey collections. The departing bees gorge on honey before leaving, while the remaining, considerably smaller hive takes time to resume normal production levels.

Dealing with the two primary motivations for swarming–overcrowding and poor ventilation–represents a beekeeper’s best chance at preventing a swarming issue. To efficiently address congestion in the hive, beekeepers should anticipate the requirements of their growing hive by creating more space in advance of a swarming situation.

Although opinions on these techniques vary, methods of enlarging a hive include reversing the hive body (which entails switching the top and bottom boxes) in the spring or otherwise decongesting the brood nest. A more drastic measure is to split the brood nest between two hives the original one and a new one. One will inherit the new queen and the other will need to raise a new queen.

Some think that another method, namely use of a barrier known as queen excluder prior to the first nectar flow of the season. However this has no impact on the brood nest size and is really intended to keep the honey and brood nest segregated, engineering an orderly hive for the benefit of the beekeeper! Indeed it could be argued that use of a queen excluder actually encourages swarming by constraining potential growth of the brood nest.

A few techniques for improved ventilation, meanwhile, include ensuring that the inner cover’s ventilation hole is fully open and drilling small holes in the upper deep region of each honey super. The latter method also provides more hive entrances for the bees.