Genetically Modified Bacteria Used To Create Precursor To Morphine

Is desktop morphine production on its way? Tiny Devil/Shutterstock

Although it’s mostly harmless, some strains of the bacterium E. coli can cause fairly dangerous health problems, like infections or food poisoning. A team of Japanese bioengineers has now genetically engineered this common gut microbe in order for it to take on a very different role: producing painkiller precursors chemically related to morphine, as reported in a new study in Nature Communications.

Morphine is an opiate, sourced from raw opium from the seeds of the opium poppy. In what is typically a long, drawn out process, the poppies are grown by licensed farmers, which are then shipped to pharmaceutical companies in order to extract a significant quantity of drug molecules. A single batch of morphine-based painkillers can take a year to make.

Scientists have been exploring alternative, faster morphine production methods for some time now, and a 2015 study revealed how genetically modified yeast cells are able to produce certain opiates. This process couldn’t create morphine, but it could produce compounds that are part of the chemical family that morphine belongs to.

This new study reveals a way to make E. coli produce thebaine, another compound related to morphine, but importantly one that is generated just prior to morphine in the traditional process. Thebaine, along with morphine and codeine, is one of the three principle painkillers derived from opium.

E. coli’s energy-producing (metabolic) processes are not only highly efficient, but the biochemical reactions involved somewhat resemble some of the steps used in the traditional process to produce opiates. This research team therefore wondered whether it could be put to use converting nothing more than sugar into the sought-after painkillers.

Poppy seeds – the traditional source of chemicals required to make opiate painkillers. Linda Vostrovska/Shutterstock

Genes from opium poppies were spliced into E. coli, along with several genes from other bacteria. The combination of these additional genes modified E. coli’s metabolic processes in such a way that thebaine could be produced.

“Morphine has a complex molecular structure; because of this, the production of morphine and similar painkillers is expensive and time-consuming,” said study co-author Fumihiko Sato, a bioengineer at Kyoto University, in a statement. “But with our E. coli, we were able to yield 2.1 milligrams of thebaine in a matter of days from roughly 20 grams of sugar.”

This new process is so efficient that it produces 300 times more thebaine than using the equivalent amount of yeast. If this process is refined further in order to produce morphine itself, it could revolutionize the pharmaceutical market.

The yeast-based method actually came in for some ethical criticism when it was published, with some saying that such desktop methods could result in unregulated opiate production. Although yeast is indeed readily available, four separate E. coli strains are required for this new method to work – strains that most people won’t be able to get their hands on without considerable difficulty.

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