Homebrewed Prescription Drugs, From Genetically Engineered Yeast, Now Growing Industry
Imagine being able to produce opioid painkillers, antibiotics, and cancer drugs in the same way you’d brew beer, without ever leaving your home. Researchers at the University of California, Berkeley are hoping their latest research will lead to just that, with the help of a genetically engineered strain of yeast.
Poppy plants typically undergo over a dozen different chemical processes before ending up as the opiates morphine, codeine, and thebaine. From there, pharmaceutical factories process the drugs further into higher-value drugs, like oxycodone and hydrocodone. Hoping to replicate this process without using poppy plants, a growing field of research involves genetically engineering yeast so that it can be thrown into a vat with sugar (glucose) and converted into these drugs.
In a new study published in the journal Nature Chemical Biology, researchers describe how they were able to achieve the first half of this process. Their modified strain of yeast was able to synthesize reticuline, which can be turned into the aforementioned opiates, from a derivative of glucose called tyrosine. “What you really want to do from a fermentation perspective is to be able to feed the yeast glucose, which is a cheap source of sugar, and have the yeast do all the chemical steps required downstream to make your target therapeutic drug,” said John Dueber, a bioengineer at UC Berkeley, in a press release.
While the team still needs to determine how to start the process with glucose rather than tyrosine, the steps they would have to take to go from reticuline to higher-value drugs has already been described in yeast, said Vincent Martin, a microbiologist at Concordia University in Quebec. Some of those steps were completed by Christine Smolke of Stanford University, who used a modified yeast strain — with three genes from the poppy plant and two from a bacterium that eats poppy waste — to convert thebaine into higher-value drugs.
The only hurdle left was to get yeast to start from the beginning. The current study takes care of that problem; reticuline is a precursor to thebaine. For their study, researchers took the enzyme responsible for giving beets their bright colors, modified its genes, and added them to the modified yeast. This allowed the yeast to convert tyrosine into dopamine, which can then be converted into reticuline and other drugs. Those drugs wouldn’t only be opioids, either. As part of a class of bioactive compounds called benzylisoquinoline alkaloids (BIAs), reticuline may also prove useful in the development of other drugs treating everything from spasms to infections.
Making opiates in a lab would dramatically reduce the need to rely on the few countries where poppy is legally grown to produce high yields. Instead, we’ll be able to develop them in a lab. While Dueber expressed concern that policies should be discussed now to prevent abuse and at-home opiate production, Smolke said there are steps that can be taken to avoid these problems. For example, the yeast will likely be engineered to be less addictive, to bypass processes that turn it into morphine, which is often processed into heroin. She also told Wired the process would require “very specialized and highly controlled equipment and conditions, which are not readily available to non-specialists.”
Still, with the research moving so fast — the current study took only six months — the time to think about policies is now, Dueber said. “We’re likely looking at a timeline of a couple of years, not a decade or more, when sugar-fed yeast could reliably produce a controlled substance,” Dueber said. “The time is not to think about policies to address this area of research. The field is moving surprisingly fast, and we need to be out in front so that we can mitigate the potential for abuse.”
Source: DeLoache W, Russ Z, Narcross L, Gonzales A, Martin V, Dueber J. An enzyme-coupled biosensor enables (S)-reticuline production in yeast from glucose. Nature Chemical Biology. 2015.