Instead of Poppies, Engineering Microbes to Make Morphine

This article was originally published on The Conversation.

The past few decades have seen enormous progress being made in synthetic biology the idea that simple biological parts can be tweaked to do our bidding. One of the main targets has been hacking the biological machinery that nature uses to produce chemicals. The hope is once we understand enough we might be able to design processes that convert cheap feedstock, such as sugar and amino acids, into drugs or fuels. These production lines can then be installed into microbes, effectively turning living cells into factories.

Taking a leap in that direction, researchers from Stanford University have created a version of bakers yeast (Saccharomyces cerevisiae) that contains genetic material of the opium poppy (Papaver somniferum), bringing the morphine microbial factory one step closer to reality. These results published in the journal Nature Chemical Biology represent a significant scientific success, but eliminating the need to grow poppies may still be years away.

If dog has been mans best friend for thousands of years or more, the humble yeast has long been mans second-best friend. The single-cell organism has been exploited by human societies to produce alcoholic beverages or bread for more than 4,000 years.

Like any animal or plant that mankind domesticated, there has been a particular interest in the study and optimisation of yeast. When breeding turned into a scientific discipline, it quickly became a model organism for biological experiments. And in 1996, its complete genome was the first sequenced from a eukaryotic organism the more advanced tree of life. This extensive knowledge of yeast biology makes it an attractive platform for synthetic biology.

In the new study, Christina Smolke and her team further show that yeast could be a good candidate for the production of opioids a class of drugs that includes morphine. To achieve this transformation, Smolke would need a complete biological pathway required to produce complex opioids.

In 2008 she got the first hint on successfully fermenting simple sugars to make salutaridine, an opioid precursor. Then in 2010, a Canadian team identified the last two missing pieces of the morphine puzzle in the genome of opium poppy.

Using these biological parts from plants, together with some from bacteria, Smolke has now created yeast that can produce many natural and unnatural opioids. All it takes is to feed the microbes an intermediary molecule extracted from the poppy plant called thebaine.

These results bring the technology one step closer to microbial factories that can produce pharmaceutical molecules in a tank rather than in the field. What is left now is for Smolke to find a way to turn salutaridine into thebaine efficiently. Filling this gap may allow her to create a yeast strain producing opioids directly from sugars.

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Instead of Poppies, Engineering Microbes to Make Morphine