A new way to make a medicine
Researchers have engineered yeast to produce forskolin — a rare medicinal compound found in one species of plant.
Unlike animals, plants cannot move away from a herbivore or other threats. Instead, they have evolved to produce a vast array of chemical compounds to protect themselves. Some of these compounds are also important to humans, for example, as medicines or fragrances. Plants usually only produce small amounts of these compounds in mixtures with many other compounds, which makes it difficult to purify them. As a result, the methods of purifying the compounds may require huge amounts of plant material, or be expensive and not environmentally friendly. One solution to this would be to genetically engineer microbes like bacteria or yeast to produce the compounds instead. In order to do that, we need to understand exactly which enzymes the plant uses to make each compound and introduce them into suitable microbes.
A compound called forskolin has been used since ancient times in traditional Indian medicine to treat conditions like high blood pressure, asthma and heart complications. Forskolin is found exclusively in the root of a plant called Coleus forskohlii, which is native to India and south-east Asia. It is stored inside cells within the bark of the root in structures called oil bodies, which are similar to oil drops. However, it is not known where forskolin is made, or which enzymes are involved.
Irini Pateraki, Johan Andersen-Ranberg and colleagues set out to uncover how C. forskohlii (which is also known as Plectranthus barbatus) produces this compound. The experiments show that forskolin is produced within the cells that contain the oil bodies. A technique called RNA sequencing was used to identify several genes that are highly active in these cells and encode enzymes that could potentially be involved in producing forskolin. Further experiments demonstrated that these enzymes drive a cascade of chemical reactions that convert a molecule called 13R-manoyl oxide into forskolin. Next, Pateraki, Andersen-Ranberg and colleagues inserted the genes into yeast cells that could already produce 13R-manoyl oxide, which allowed the yeast to produce relatively high amounts of forskolin.
These findings show that it is possible to identify the genes involved in the production of medicinal compounds in a relatively short amount of time. This knowledge will aid the development of a method that can be used to produce forskolin and other similar compounds on a large scale without needing to harvest C. forskohlii plants.
To find out more
Read the eLife research paper on which this eLife digest is based: “Total biosynthesis of the cyclic AMP booster forskolin from Coleus forskohlii” (March 14, 2017).
Listen to Irini Pateraki discuss engineering yeast to make forskolin in episode 38 of the eLife podcast.
