UC Berkeley researchers complete steps for alternative pathway to narcotic manufacture, call for discussion

Zachary Russ/Courtesy

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Researchers have completed key steps needed to facilitate a pathway in an engineered strain of yeast that would allow the synthesis of morphine and codeine, among other drugs.

The study, published online Monday in the journal Nature Chemical Biology by UC Berkeley bioengineer and assistant professor of bioengineering John Dueber and by Concordia University microbiologist Vincent Martin, highlights the possibility of being able to engineer the pathway of highly bioactive compounds that could lead to the creation of opiates such as codeine, morphine and thebaine — a precursor to oxycodone and hydrocodone — or antispasmodic and antibiotic medicine. The study has prompted a call for regulation on security and health risks raised by the synthetic biology community.

The researchers found that by adapting an enzyme, tyrosine hydroxylase, from beets that is naturally used in the production of vibrant pigments for a different use, yeast could convert tyrosine into dopamine. The production pathway, according to co-author and campus graduate student Zach Russ, is the conversion of tyrosine into the molecule L-DOPA, then from dopamine into reticuline, which could create myriad drugs, including anti-spasmodic, anti-cancer and anti-addiction medicine.

“Right now, the big deal is we made an enzyme that takes tyrosine and turns it into L-DOPA, and getting one of those enzymes that works with yeast is the missing step for making anything with dopamines,” Russ said.

L-DOPA, used for Parkinson’s treatment, and tyrosine help the creation of reticuline, a common precursor to many opioids. After discovering this, Russ said, the study was halted and then published to prompt discussion about regulation.

According to Kenneth Oye, associate professor of political science and engineering systems at the Massachusetts Institute of Technology, the “good news” is that Dueber and Martin stepped forward with the work they were doing before the pathway became complete. The warning allows time for deliberation on what response is appropriate, rather than completing the pathway only to risk illicit use of the research, Oye said.

Oye, who co-wrote an article in the journal Nature about regulating “home-brew” opiates, said it is recommended that researchers modify their final product to be less appealing for illicit use. Oye said the second set of considerations includes having securer laboratories where work of high potential value that has serious health effects — such as opium and morphine production — will not be tampered with.

According to Oye’s article in Nature, by providing a simpler and more manipulable means of producing opiates, the yeast research could ultimately lead to cheaper, less addictive, safer and more-effective pain-relieving drugs. In generating a self-replicating drug source, people’s access to opiates could dramatically increase.

“There is real value in the research being done,” Oye said. “We recommend the people doing the technology sit back and think very hard about modifying what they are doing.”

Also involved in the study are lead author and campus doctoral student William DeLoache, co-author Andrew Gonzalez of UC Berkeley and Lauren Narcross of Concordia University.

Robert Tooke is a news editor. Contact him at [email protected] and follow him on Twitter @robertono_t.