Genetically Modified Yeast Strains Produce Opioid Drugs
Imagine being able to take genetically modified yeast to “brew” morphine and other opioid drugs, such as hydromorphone, hydrocodone, and oxycodone. That is exactly what a group of researchers from Stanford University have done, according to reports in Nature Chemical Biology and Science.1,2
The development of morphine is derived from the opium poppy plant. However, the production can involve many challenges: "susceptibility of the plants to climate and disease, one annual growing season, the need for chemical processing, and social/political factors related to illicit use," noted a report from the National Center for Complementary and Alternative Medicine.3 "Genetically engineering the plants can be slow and demanding due to long generation times, lack of a genome map, and limited tools for genetic manipulation."
Turning microbes into miniature factories, the Stanford researchers say, provides an alternative strategy for producing opioids. Building on previous work using the yeast Saccharomyces cerevisiae, the researchers devised a strategy to develop opioid-generating pathways within the microorganisms. They describe how they added genes from the opium poppy plant (Papaver somniferum) and a bacterium (Pseudomonas putida) to yeast to produce target opioids.1
However, the current process requires the compound thebaine as the starting material for producing the opioids. "Here, we engineered yeast to produce the selected opioid compounds thebaine and hydrocodone starting from sugar," wrote the author in the recent issue of Science.2 "We combined enzyme discovery, enzyme engineering, and pathway and strain optimization to realize full opiate biosynthesis in yeast. The resulting opioid biosynthesis strains required expression of 21 (thebaine) and 23 (hydrocodone) enzyme activities from plants, mammals, bacteria, and yeast itself."
This is a proof-of-principle, noted the researchers, but major hurdles remain. "This and other key challenges—such as increasing the amount of chemical produced and preventing unproductive side reactions from occurring—remain in developing yeast (and processes) that can achieve industrial-scale microbial opioid production," noted the researcher.
Despite these hurdles, the research is promising and demonstrates the potential for developing a sustainable and secure yeast biomanufacturing platform for opioids. "Open discussions of options for governing this technology are also needed in order to responsibly realize alternative supplies for these medically relevant compounds," they noted.