Bioengineers have hacked the DNA of yeast, reprograming cells to make opium-based medicines such as morphine via an extension of the basic brewing process which makes beer.
Associate Professor of Bioengineering Christina Smolke of Stanford University has already spent a decade genetically engineering yeast cells to reproduce the biochemistry of poppies with the ultimate goal of producing opium-based medicines, from start to finish, in fermentation vats.
“We are now very close to replicating the entire opioid production process in a way that eliminates the need to grow poppies, allowing us to reliably manufacture essential medicines while mitigating the potential for diversion to illegal use,” says Smolke, who outlines her work in the journal Nature Chemical Biology.
Smolke and colleagues added five genes from two different organisms to yeast cells. Three of these genes came from the poppy itself, and the others from a bacterium which lives on poppy plant stalks.
This multi-species gene mashup was required to turn yeast into cellular factories that replicate two, now-separate processes: how nature produces opium in poppies, and then how pharmacologists use chemical processes to further refine opium derivatives into modern opioid drugs such as hydrocodone.
Plant-derived opium has been used for centuries.
Morphine is one of three principal pain killers derived from opium. As a class they are called opiates.
The other two important opiates are codeine, which has been used as a cough remedy, and thebaine, which is further refined by chemical processes to create higher-value therapeutics such as oxycodone and hydrocodone, better known by brand names such as OxyContin and Vicodin.
Legal poppy farming is restricted to a few countries including Australia and is supervised by the International Narcotics Control Board, which seeks to prevent opiates such as morphine from being refined into illegal heroin.
The thrust of Smolke’s work has been to pack the entire production chain, from the fields of poppies, through all the subsequent steps of chemical refining, into yeast cells using the tools of bioengineering.
What Smolke’s team has now done is to carefully reprogram the yeast genome, the master instruction set which tells every organism how to live, to behave like a poppy when it comes to making opiates.
It takes about 17 separate chemical steps to make the opioid compounds used in pills. Some of these steps occur naturally in poppies and the remaining via synthetic chemical processes in factories.
Smolke’s team wanted all the steps to happen inside yeast cells within a single vat, including using yeast to carry out chemical processes which poppies never evolved to perform such as refining opiates into more valuable semi-synthetic opioids such as oxycodone.
The scientists have one more hurdle in order to achieve the goal of pouring sugar into a stainless steel vat of bioengineered yeast and skimming off specific opioids at the end of the process.
They must perform another set of bioengineering hacks to connect the major advances they have made over the past decade.
“We are already working on this,” she says.
Smolke said it could take several more years to perfect these last steps in the lab and scale up the process to produce large sized batches of bioengineered opioids pharmacologically identical to today’s drugs.
“This will allow us to create a reliable supply of these essential medicines in a way that doesn’t depend on years leading up to good or bad crop yields,” Smolke says.
“We’ll have more sustainable, cost-effective, and secure production methods for these important drugs.”
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