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Cough Suppressant Produced from Engineered Yeast Cells

Brewer's yeast

Scanning electron microscope image of Saccharomyces cerevisiae, or brewer’s yeast (Mogana Das Murtey and Patchamuthu Ramasamy, Wikimedia Commons)

3 April 2018. A bioengineering group created a process for producing a cough suppressant in the lab, usually derived from opium poppies, but instead from genetically modified brewer’s yeast. Researchers from Stanford University’s medical school in California describe the process in yesterday’s issue of Proceedings of the National Academy of Sciences (paid subscription required).

The team from the bioengineering lab of Christina Smolke is seeking simpler and more economical ways of making pharmaceuticals needed by large segments of the population, but by synthesizing chemical processes from natural sources. In this project, the researchers devised an alternative process for making noscapine, a natural cough suppressant and possible drug for treating cancer with fewer adverse side effects of most chemotherapy drugs. A big problem with noscapine, however, is the drug is usually made from opium poppies, which can be grown legally, but under carefully controlled and highly restricted conditions.

Smolke and colleagues started with brewer’s yeast, a well-studied single-cell organism formally known as Saccharomyces cerevisiae. To synthesize noscapine from brewer’s yeast, the authors needed to add 25 genes from other plant and animal genomes, even from rats, as well as variations or overexpressed yeast genes. Mammals’ genes are needed to produce dopamine, an intermediate product for synthesizing noscapine, produced in nerve cells, but rarely found in plant cells. Adding these non-native genes to yeast helped produce the enzymes needed for noscapine.

In addition to making the enzymes, the researchers needed to configure their production in the engineered yeast to generate synthetic noscapine. For this task, the researchers used the gene editing technique Crispr, short for clustered regularly interspaced short palindromic repeats. With Crispr, the team altered the order of the inserted genes to produce noscapine more efficiently. Further engineering of the enzymes, along with refinements in the engineered yeast’s fermentation process, enabled the team to boost production of noscapine to usable quantities.

The Stanford team extended the process by adding modified derivatives of tyrosine, an amino acid found in neurotransmitter chemicals in the nervous system, as well as melanin the produces pigments in skin color. This extension of the process, says the authors, suggests engineering yeast offers a platform for synthesizing certain alkaloid compounds, which can be made into substitutes for some dangerous opioid drugs, as well as other neurological, autoimmune, and cancer drugs.

“We’re no longer limited to what nature can make,” says Smolke in a university statement. “We’re moving to an age where we can borrow nature’s medicine-manufacturing processes and, using genetic engineering, build miniature living factories that make what we want.”

Stanford applied for a patent on the technology with Smolke and first author Yanran Li, now on the faculty at University of California in Riverside, as inventors. Smolke co-founded the company Antheia Inc. in 2015 licensing the lab’s research synthesizing alkaloid compounds from engineered yeast, and serves as the company’s CEO. Antheia since received a series of Small Business Innovation Research grants from National Institutes of Health and National Science Foundation to advance the company’s technology.

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