DIY Morphine: Bioengineered Yeast Could Be Used to Brew Opiates

But researchers are calling for regulations.

May 18 2015, 5:19pm

Opium field in Afghanistan. Image: UN/UNODC/Zalmai

In the future, if you mash together the right strain of yeast and some basic fermentation skills, making homebrewed opiates might be as simple as brewing beer. As a team of researchers have just found a way to make make morphine from glucose using a bioengineered strain of yeast.

In a study published today in Nature Chemical Biology, UC Berkeley bioengineer John Dueber collaborated with Vincent Martin, a microbiologist at Concordia University, to replicate the early steps of a morphine-production pathway with an engineered strain of yeast. Combining seven years' worth of research, the pair were finally able to synthesize reticuline, an alkaloid found in poppies, from tyrosine, a glucose derivative.

"Getting to reticuline is critical because from there, the molecular steps that produce codeine and morphine from reticuline have already been described in yeast," Martin said in a press statement.

But the discovery also poses certain challenges. In a commentary piece published in Nature today, policy analysts Kenneth Oye, Tania Bubela and J. Chappell H. Lawson warn that "in principle, anyone with access to the yeast strain and basic skills in fermentation would be able to grow morphine producing yeast using a home-brew kit for beer-making."

They also stated that, "if the modified yeast strain produced 10 grams of morphine, users would need to drink only 1–2 millilitres of the liquid to obtain a standard prescribed dose," adding that "researchers predict that it will be only a few years—or even months—before a single engineered yeast strain can complete the entire process."

Over the last decades, researchers have been trying to enable the production of therapeutic drugs by working on replicating a complicated 15-step chemical pathway in poppy plants. While Martin explained that researchers have used E. coli or yeast microbes to recreate different sections of the poppy's drug pathway, both he and Dueber's research finally permits a single organism to carry out the whole process by itself.

Yeast cells producing the yellow beet pigment betaxanthin, which UC Berkeley researchers used to quickly identify key enzymes in the production of benzylisoquinoline alkaloids (BIAs). BIAs are the metabolites in the poppy plant that could lead to morphine, antibiotics and other pharmaceutical agents. Image: William DeLoache/UC Berkeley

The study's principal investigator, Dueber, explained in a press statement that, "what you really want to do from a fermentation perspective is to be able to feed the yeast glucose, which is a cheap sugar source, and have the yeast do all the chemical steps required downstream to make your target therapeutic drug."

"With our study, all the steps have been described, and it's now a matter of linking them together and scaling up the process. It's not a trivial challenge but it's doable," he added.

Further developments in synthetic biology might allow researchers to use sugar-fed yeast as a platform for producing morphine and other antibiotic and anti-cancer drugs more cheaply.

But if the tech falls into the wrong hands, it could potentially spur a whole illicit homegrown drug trade.

According to Dueber, sugar-fed yeast could produce a controlled substance in a couple of years. That's why it's important to be looking now at potential dangers and challenges that the technology might bring, and urging regulations for it from policymakers and lawmakers.

Martin explained that while it was difficult to genetically build the yeast strain, once this was built, someone could get their hands on it and use it for nefarious purposes.

Enforcing controls might not actually deter the most determined from hacking their own homebrewed drugs

"It's like any dual use technology. Like the nuclear bomb, or nuclear energy, it can be used for good and bad. So as long as long as there are regulations, you're always hoping that you can take advantage of the benefits and restrain the disadvantages," Martin told me.

Across the world, the global opiate manufacturing industry is tightly regulated, with international conventions and laws preventing diversion to illegal markets. In Australia, for example, a poppy variety rich in thebaine—which is toxic and hard to turn into morphine—is grown to produce specialist drugs such as buprenorphine and oxycodone.

Yet, despite the stringent controls and regulations surrounding the industrial production of opiates, the authors of the comment piece state that it will be hard to predict how "the International Narcotics Control Board (INCB) would react to to a new production system for opiates."

The World Health Organization reports that more than 16 million people globally use opiates illegally, and the comment paper states that as yeast is "so easy to conceal, grow and transport, criminal syndicates and law-enforcement agencies would have difficulty controlling the distribution of an opiate-producing yeast strain."

To counter these scenarios, Oye, Bubela and Lawson recommend keeping the engineering of yeast strains to licensed facilities and researchers. Companies that synthesize and sell DNA sequences should also be subject to regulations.

However, enforcing controls might not actually deter the most determined from hacking their own homebrewed drugs. "Once the knowledge of how to create an opiate-producing strain is out there, anyone trained in basic molecular biology could theoretically build it," concluded Dueber in a press statement.