Engineering Yeast to Make Non-Narcotic Cough Suppressant

Bioengineers from Stanford University have found a way to make noscapine in brewer's yeast. Noscapine is a non-narcotic cough suppressant that occurs naturally in opium poppies.

Noscapine's cough-suppressing capability was discovered in 1930, and the drug has been widely used since the 1960s throughout Asia, Europe, and South America, as well as in Canada, Australia, and South Africa. But the only viable source of noscapine is opium poppies. Tons of noscapine are extracted annually from the plant, which takes a full year to mature. The yeast that was bioengineered can spew out substantial amounts of noscapine in three or four days. The investigators achieved this result by stitching three separate sections of the noscapine biosynthetic pathway into a single yeast strain.

Dopamine is a key intermediate in noscapine synthesis, so the researchers spliced in rat genes that direct dopamine production. The scientists used CRISPR to alter inserted genes so that the enzymes for which they coded would work most efficiently in their new home. They also souped up the yeast's production of a chemical whose levels would have otherwise been too low to sustain robust noscapine production.

The researchers inserted 25 foreign genes into the one-celled fungus to turn it into an efficient factory for producing noscapine. Many of the inserted genes came from the poppy, but several came from other plants and even from rats. The researchers also modified some of the plant, rat and yeast genes, as well as the medium in which the yeast proliferates, to help everything work better together. The result was an 18,000-fold improvement in noscapine output, compared with what could be obtained by just inserting the plant and rat genes into yeast.

For more, read the news article from Stanford Medicine News Center.