Researchers at the California Institute of Technology have developed a way to churn out large quantities of drugs using biofactories.
Assistant professor of chemical engineering Christina Smolke and graduate student Kristy Hawkins genetically modified common baker’s yeast (Saccharomyces cerevisiae) so that it contained the genes of several plant enzymes.
The enzymes allow the yeast to produce a chemical called reticuline, which is a precursor for many different classes of benzylisoquinoline alkaloid (BIA) molecules.
The BIA molecules are a large group of chemically intricate compounds, such as morphine, nicotine, and codeine, which are naturally produced by plants.
BIA molecules exhibit a wide variety of pharmacological activities, including antispasmodic effects, pain relief, and hair growth acceleration. Other BIAs have shown anticancer, antioxidant, antimalarial and anti-HIV potential.
However, the natural plant sources of BIAs accumulate only a small number of the molecules, usually ’end products’ such as morphine and codeine that, while valuable, can’t be turned into other compounds, thus limiting the availability of useful new products.
To their reticuline-producing yeast, Smolke and Hawkins added the genes for other enzymes, from both plants and humans, which allowed the yeast to efficiently generate large quantities of the precursors for sanguinarine, a toothpaste additive with antiplaque properties, berberine, an antibiotic and morphine.
The researchers are now in the process of engineering their yeast so that it will turn these precursor molecules into the final, pharmacologically useful molecules.
Smolke estimates that the system could be used for the large-scale manufacture of BIA compounds in one to three years.
Smolke and Hawkins plan to extend their research to the production of BIAs that don’t normally exist in nature.