Genetically engineered yeast makes medicinal plant products

Tropane alkaloids, like most other plant natural products, are still typically extracted from natural sources, but this approach has many pitfalls. For instance, vulnerability to weather and market fluctuations can limit access for both patients and researchers, and extraction can be environmentally harmful. In addition, plants typically contain very low levels of these active ingredients.

Srinivasan and Smolke report an alternative way to make tropane alkaloids that could relieve these limitations – using engineered strains of the baker’s yeast Saccharomyces cerevisiae.

Plants produce a variety of specialized compounds that help them to adapt and survive. Biosynthesis of these natural products often involves lengthy metabolic pathways that have complex dynamics and regulation. One of the major achievements in the field of metabolic engineering has been the development of microorganisms that can produce plant natural products. However, the approach is far from routine because the enzymes involved in biosynthesis are often unknown, might be inactive in microbial hosts, and can be segregated across different plant subcellular compartments, cells or tissues.

Srinivasan and Smolke have overcome these challenges to produce a strain of S. cerevisiae that converts simple sugars and amino acids into two tropane alkaloids, hyoscyamine and scopolamine. These tropane alkaloids block the action of the neurotransmitter molecule acetylcholine. They are used to treat nausea, gastrointestinal problems, excessive bodily secretions and neuromuscular disorders, including Parkinson’s disease.