Engineered yeasts can be induced to synthesize morphine and other natural and semisynthetic analogs, reports a study published online this week in Nature Chemical Biology. This work demonstrates an important step toward engineered opioid production.
Opiates such as morphine are commonly used in medicines, but their chemical complexity means that commercial production is limited, with current strategies relying on plant extraction. Engineered biosynthesis of morphine and related molecules by microorganisms such as E. coli and yeast would greatly simplify production. However, not all of the genes in the biosynthetic pathway have been identified, and of those that are known, only a few have been tested in different host species.
To explore the production of opiates in yeast, Christina Smolke and colleagues introduced a series of enzymes into yeast to convert the chemical intermediate, thebaine, into morphine and related molecules. The authors used metabolic engineering strategies to optimize the relative amounts of the different enzymes and to spatially separate them within the yeast cells to mimic their localization in more complex plant cells. Finally, by adding enzymes identified from bacteria evolved to act on opioids, the authors were able to make additional products such as hydrocodone and oxycodone. Further efforts will be required to build the entire pathway.
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