Giving yeast the human ability to taste and smell

Environment and sustainability 8. sep 2022 4 min Professor Sotirios Kampranis Written by Kristian Sjøgren

Researchers have developed yeast that can detect cannabinoids. This yeast can be used to identify new cannabinoids for treating people with many inflammatory or neurodegenerative disorders, such as multiple sclerosis. The yeast can also detect illegal drugs and reveal whether people are under their influence.

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People’s ability to taste and smell is a function of hundreds of different G protein–coupled receptors (GPCRs), each of which can bind to and recognise different molecules.

Examples include the taste of roast pork or the smell of freshly baked bread, both of which activate different GPCRs that send a signal to the brain.

In the human nose alone, 400 different GPCRs enable us to detect and distinguish between, for example, the smell of roses and the smell of rotting cabbage.

Yeast does not have the same potential to sense its surroundings as humans. In fact, it can only sense whether there is a potential partner or sugar in its surroundings. The yeast focuses on pheromones and food – no more no less.

Now researchers have modified the sensing ability of yeast, enabling it to smell and taste as people do. In particular, the researchers have given the yeast the ability to detect cannabinoids, and this has great perspectives for developing new medicines.

“We have manipulated the yeast so that it can detect cannabinoids and then transmit a signal, telling us that cannabinoids are present near the yeast and at what concentrations. We can use yeast to screen thousands of plants for compounds that have therapeutic potential, and we can also investigate whether people are under the influence of drugs or whether someone is trying to smuggle illegal cannabinoids through airport security,” explains a researcher behind the development of the yeast, Sotirios Kampranis, Professor of Biochemical Engineering at the Department of Plant and Environmental Sciences, University of Copenhagen.

The research has been published in Nature Communications.

Cannabinoids induce yeast cells to glow red

Sotirios Kampranis and colleagues Karel Miettinen and Nat Leelahakorn replaced the GPCR that yeast uses to sense a partner with the human GPCR that recognises cannabinoids.

Then they introduced a set of genes into the DNA of the yeast, so that when they sense cannabinoids in the environment, they either glow fluorescent green, produce a red pigment or light up like a firefly.

Sotirios Kampranis explains that the ability to sense cannabinoids has a very special function for people that actually has little to do with cannabis.

The function of the human cannabinoid receptors play a major role in the body’s inflammatory response, since the receptors are designed to sense a group of molecules called endocannabinoids. These are compounds that we humans produce and that act as anti-inflammatory agents and regulate the immune system.

“The human receptors also respond to natural substances such as cannabinoids produced by the cannabis plant. Like cannabinoids, other natural substances can have a therapeutic effect on people with various inflammation-related disorders such as multiple sclerosis and other autoimmune diseases. Thus, our yeast can help to identify new natural substances that may have therapeutic potential,” says Sotirios Kampranis.

Discovering potential drugs in Mexican medicine plants

According to Sotirios Kampranis, yeast can be especially useful in developing new medicines. This is expensive, but the yeast can very quickly and cost-effectively find substances that can modulate human receptors and thus have potential in reducing illness.

The researchers validated the potential of their yeast by examining the content of cannabinoids in 54 randomly chosen Mexican traditional medicine plants.

The researchers blended the leaves, stems and roots from the plants and then added yeast. If the yeast glowed red when it came into contact with the extract from the plants, there were cannabinoids in the samples, which meant the researchers had hit the jackpot.

“We found a new and so far unknown cannabinoid and examined it more closely, finding that it very strongly activated the cannabinoid receptor. It may have therapeutic potential. Further studies must determine this, but we can always use more medicines,” explains Sotirios Kampranis.

Yeast can detect narcotics

Another application of the yeast is within police efforts to find drugs in airports or to determine whether people are under the influence of drugs.

For this purpose, the researchers developed a portable device that can identify the presence of cannabinoids in point-of-use situations outside the laboratory.

The device can be 3D-printed or assembled from materials easily purchased on the web, is compatible with a mobile telephone and can be used to test for cannabinoids in saliva, urine or a sample from a suitcase. The device uses the phone’s camera to determine whether the yeast lights up, and getting the answer only takes 15 minutes.

Sotirios Kampranis explains that the most ingenious thing about the device is that the yeast is not selective about the type of cannabinoids it detects. It only responds to the cannabinoid receptors being activated.

“This means that we can test for both natural cannabinoids and designer drugs, which are chemical substances with very different structures but with the same effect as cannabinoids. We can also test for substances that have not yet been discovered or developed,” adds Sotirios Kampranis.

Detecting much more than cannabinoids

By developing this cannabinoid-responsive yeast, the researchers have shown that yeast can be equipped with senses similar to those of humans. The potential is therefore much greater than simply detecting cannabinoids.

Sotirios Kampranis says that it could also be useful to make yeast that can detect new opioids that can be used in relieving pain and that do not have the same addictive effects as morphine.

Further, working with the system is so easy that small laboratories can use it without the need for expensive equipment and trained personnel. This democratises research in various fields, which can help to accelerate the development of new drugs, since many more researchers can help to identify promising drug candidates.

Sotirios Kampranis believes that this opens up some interesting perspectives since 35% of all drugs on the market target a GPCR.

Other possibilities are to develop yeast that can identify pollutants in water or soil samples and pesticides in fruit and vegetables or determine whether various foods smell as they should or are going bad.

As long as a chemical interacts with a GPCR in humans, researchers can design yeast that can identify it.

“Many areas can be improved with artificial senses that can identify the presence of various substances. Only imagination sets the limit,” concludes Sotirios Kampranis.

A GPCR-based yeast biosensor for biomedical, biotechnological, and point-of-use cannabinoid determination” has been published in Nature Communications. The Novo Nordisk Foundation awarded a grant to Sotirios Kampranis in 2016 for the project Transforming Yeast Organelles into Microfactories for the Compartmentalization of Complex Biosynthetic Pathways and an Ascending Investigator Grant in 2019 for the project Biotechnological Production of Structurally Complex Plant High-value Compounds.

I work in the area of Synthetic Biology/Metabolic Engineering, aiming to devise methods to produce high-value natural products in engineered organisms...

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