Researchers reported this week in Nature Chemical Biology of a potential path to manufacturing opiates in genetically-engineered yeast that mimicks the way the compounds are synthesised in poppies. The research comes with a commentary from two MIT (Massachusetts Institute of Technology) professors and a third from University of Alberta, describing how it’s only a matter of time before this new manufacturing route becomes reality.
Researchers from the University of California at Berkeley and Concordia University in Montreal in their paper detail a way to coax yeast to make reticuline, a critical intermediate in producing morphine and other opiates, while other research from the University of Calgary adds the final piece to the puzzle.
“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 analgesics,” the authors write in the commentary. “And in generating a drug source that is self-replicating and easy to grow, conceal and distribute, the work could also transform the illicit opiate marketplace to decentralized, localized production. In so doing, it could dramatically increase people's access to opiates.”
The technology to make morphine from glucose using yeast has been seven years in the making thanks to the three groups of researchers who introduced genetic components from poppy, beetroot and a soil bacterium into the yeast genome, thus creating strains that can perform various parts of the glucose-to-morphine pathway.
A fourth group of researchers, meanwhile, developed a strain that can convert one of the intermediate compounds, (S)-reticuline, into another, (R)-reticuline.
“With this final step realized, the creation of a single strain of yeast capable of executing the entire pathway is feasible,” the authors note, though no one has yet produced the strain. Though according to the New York Times, several academic teams are trying, and the Stanford lab of Christina Smolke is a leader, and expects to publish a yeast strain by next year.
Homebrew opiates?
And as far as the homebrew recipe, the commentators note 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. 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. (Current strains are not this efficient, but titres in this range and even tenfold higher have been achieved for other commercially relevant metabolic products.)”
But how viable this new production scheme will be for even testing whether the new products are safer than poppy-produced opiates may never see the light of day.
“It is difficult to predict how the main international body, the International Narcotics Control Board (INCB), would react to a new production system for opiates,” the authors note. “The INCB is unlikely to slash current opium-production quotas and disrupt current legal opiate-trade patterns to accommodate yeast-based production. This would limit the ability of new producers to enter the market.”
In conclusion, the professors make four immediate recommendations around engineering, security, screening and regulation, including that efforts “should be made to keep opiate-producing yeast strains in controlled environments that are licensed by regulators.”
In addition, yeast strains “should be designed to make them less appealing to criminals. For example, strains could be engineered to make only opiates with limited street value, such as thebaine.”