Berries

The first steps towards strawberry pills against Alzheimer's

Bacteria and microorganisms Biological systems Cells Enzymes and proteins Fermentation Genes and genomes Synthetic biology

In a few years, you could probably take a strawberry pill to prevent Alzheimer's or red wine pills against heart diseases. Researchers have studied the beneficial molecules of berries and figured out how to produce the molecules on a large scale in bacteria.

In order to avoid a variety of lifestyle diseases, what would you rather do: eat an entire kilogram of berries a day or just one diet supplement pill?

Even though many of us love berries, the first option would probably give us a stomach ache. In order to prevent this, the project BacHBerry has studied the beneficial molecules in berries and their impact on health and disease. The research also focused on how these molecules can be produced by bacteria instead of plants.

"People often ask: ’Why can’t I just eat berries instead of a pill to get the beneficial effects?’ My answer is: of course, you can do that, but it requires huge areas of agricultural land to grow berries for everyone, and you would have to eat up to one kilogram of berries a day to get enough of the active ingredients," says Alexey Dudnik, Postdoc at the Novo Nordisk Foundation Center for Biosustainability - DTU Biosustain - and scientific coordinator of the EU-funded project BacHBerry.

The goal is to get the beneficial substances out to the consumer, for example in the form of medications and dietary supplements.

Strawberries have the key ingredient

Although berries contain a multitude of different molecules, only a few have proven to have positive effects on our health. Therefore, researchers have tried to identify novel beneficial molecules in various berries, as well as to look for further applications of some previously-described compounds.

The desirable molecules are called polyphenols, which are typically used in food as natural fragrances, flavours or colourants, and are frequently used in dietary supplements, as medicine and in cosmetics.

The researchers focused among other things on producing the polyphenol fisetin from strawberries in bacteria. Fisetin is known to reduce the risk of developing Alzheimer's and cure some of the symptoms of diabetes in mice.

"You would have to eat up to one kilogram of berries a day to get enough of the active ingredients"
Alexey Dudnik, Postdoc and scientific coordinator of BacHBerry

"It has been estimated that if a patient were to take enough fisetin by eating berries, it would require consumption of approximately 39 large strawberries every day," says Alexey Dudnik.

Another polyphenol, which was investigated in this project, is resveratrol: a powerful antioxidant found in blueberries, raspberries, and in red grapes.

The French typically drink red wine on a regular basis. Despite their reasonably large consumption of alcohol and their fatty eating habits, they suffer a lot less from heart diseases compared to other Europeans; a phenomenon called "the French paradox". This phenomenon most probably arises because of resveratrol’s protective effect against heart disease. It was also shown to prolong the lifespan in several laboratory animals.

113 different berries have been studied

To find the coveted polyphenols, the researchers collected 113 different berries from around the world, including Scotland, Portugal, Russia, China and Chile. In the initial studies, the researchers looked into the overall diversity of polyphenolic compounds in the selected species. From this screening, the researchers selected 28 berries, which contained a wide diversity of different phenolic compounds.

Extracts from the berries were tested in yeast cells, which were tailored to mimic human diseases such as Alzheimer's, Huntington's, multiple sclerosis, type 2 diabetes, inflammation, and cancer.

Many of the tested extracts had a preventive or curative effect on some of the diseases. These included selected varieties of raspberry, loganberry, blackberry, boxthorn (goji berry), and gooseberry. The chemical composition of the most promising extracts was further investigated, and several pure bioactive compounds were identified and re-validated in the disease models.

The next step for the scientists was to identify the corresponding biosynthetic pathways, and use them to further design and construct bacteria, which can produce large amounts of these beneficial molecules.

“This was achieved through the combined effort of plant scientists, microbiologists, computational biologists, and chemical engineers. The hope is also that the industry will use the tools developed in BacHBerry to bring new bioactive molecules into the market, which can then be used in new food supplements, cosmetics, medicine, and food," he says.

At the end of the BacHBerry-project, the group had actually managed to identify several new bioactive compounds and the genes in charge of synthesizing them. Furthermore, the group was able to establish the complete pipeline from discovery to pilot-scale production, which could be taken up by industry.

Video

Watch how the researchers found the interesting bioactive molecules in this documentary about the BacHBerry project. The first three minutes are primarily about the work, that has been done at DTU.

The Berrymakers from Biofaction on Vimeo.