Producing cannabinoids with microalgae

Producing cannabinoids with microalgae
Producing cannabinoids with microalgae

Perceiving the incredible biotechnological potential of diatoms, a research team took on the challenge of transforming them into biofactories to produce various molecules of pharmaceutical interest. A recently overcome challenge that opens the way to a world of possibilities.

They may be tiny, but diatoms provide at least 20% of the fixation of carbon dioxide by photosynthesis on our planet – as much as tropical forests. These unicellular algae, equipped with a silica shell, could well have other talents… including that of producing medicines.

This untapped potential interests Isabel Desgagné-Penix, professor of biochemistry at the University of Quebec at Trois-Rivières. Its goal: to transform diatoms into mini biological factories – a sustainable and economical avenue for the production of molecules of interest. The idea is promising. As proof, his team succeeded in making these microalgae produce cannabinoids – more precisely cannabigerolic acid. A world first!

Biofactories

Used for millennia in traditional medicines, cannabinoids are attracting increasing interest in Western medicine, particularly as potential treatments for chronic pain and certain neurodegenerative diseases, such as Parkinson’s.

Usually, they are obtained by extracting them from cannabis plants grown in greenhouses. However, this method gives very low yields. Another option: using microorganisms, generally bacteria or yeast, to synthesize these compounds. This consists of inserting, into these microorganisms, the genes corresponding to the proteins we wish to obtain – and they take care of the production. This is called “bioengineering”.

However, the metabolism of these bacteria and yeasts is completely different from that of plants. So much so that, to make them produce cannabinoids, it is necessary to provide them not only with the different genes involved in the manufacturing process of these molecules, but also with the precursors, i.e. the basic ingredients. It’s as if we hired a chef to make a recipe, but he demanded that we provide him with all the cooking tools (the genes) and the ingredients necessary for this recipe. Ah! And he also asks to have snacks (sugars), in order to have the energy to cook. It’s starting to do a lot!

This is where the potential of diatoms becomes interesting. These microalgae have a metabolism that more closely resembles that of so-called higher plants, such as cannabis – and this greatly simplifies bioengineering work.

Thus, diatoms immediately have, in their genome, several genes involved in the production of cannabinoids. The necessary precursors (such as acetyl-CoA) are also found there. To use the kitchen analogy, diatoms already have all the ingredients on hand and only need a few precision utensils to finalize the recipe.

A first success

Despite this, no one had yet succeeded in producing cannabinoids with diatoms. But the research group led by Isabel Desgagné-Penix has just demonstrated that it was possible! In an article published in the journal Algal Researchthe team presents two methods to achieve this: one in which the genes are directly introduced into the DNA of diatoms, the other which consists of bringing the genes into an “episome”, i.e. a fragment of DNA that remains outside the chromosome. These two methods gave similar yields, comparable to those obtained with yeast.

The production of cannabinoids is just one of the laboratory’s many goals, including the successful use of diatoms to produce alkaloids from the Amaryllidaceae plant family – a group of therapeutic molecules that includes galanthamine, used in the treatment of Alzheimer’s. And their recent prowess encourages them to continue exploring the pharmaceutical potential of diatoms.

While Professor Desgagné-Penix is ​​delighted with this progress, she remains pragmatic: there is a long way to go between their discovery and the industrialization of the process. “We wanted to do a proof of concept, it’s now done. But there is still a lot of work to do! » she concludes.

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