Scientists make new probiotics with genome editing

UNITED STATES, WASHINGTON (OBSERVATORY) — Researchers led by Prof. Johan Tevelein (VIB-KU Leuven Center for Microbiology) have discovered that Saccharomyces boulardii yeast, which has known probiotic properties , produces a unique excess of acetic acid. They also managed to find the genetic basis of this mechanism, which allowed us to control the production of acetic acid in yeast.

If the unique benefits of genetically modified S. boulardii are confirmed in animal models, this will lay the foundation for the creation of the first genetically engineered probiotic.

The background is as follows. Back in 1923, the French scientist Henri Boulard isolated a mysterious strain of yeast from a lychee fruit that grows in Southeast Asia. It turned out that these yeasts have unexpectedly strong probiotic properties.

Yeast called Saccharomyces boulardii has since begun to be used to treat diarrhea and other intestinal diseases. They are currently sold in pharmacies around the world under various brand names.

However, a recent DNA sequence analysis of the entire yeast genome revealed something new. It turned out that the strain S. boulardii is closely related to the much more well-known Saccharomyces cerevisiae, a type of yeast that is traditionally used in baking, brewing, winemaking , bioethanol production, etc.

The DNA sequences of these two yeasts are so similar that S. boulardii is now considered not as a separate species, but exclusively as a variety of S. cerevisiae. However, S. cerevisiae lacks probiotic activity, unlike S. boulardii. What was the reason for some time remained a mystery.

Trying to find a clue, a team led by Professor Johan Thevelein discovered that the hallmark of Saccharomyces boulardii was the production of large quantities of acetic acid, the main ingredient in vinegar. Acetic acid is well known as a preservative, inhibiting the growth of all microorganisms , thus the protective effect of S. boulardii became clear. But the question arose – how do these yeasts manage to produce such a large amount of acetic acid?

In the process of research, scientists were able to find two unique mutations in S. boulardii, responsible for the production of acetic acid. These mutations act as a genetic “fingerprint”, potentially allowing the isolation and identification of new strains of S. boulardii in nature.

In the meantime, based on this knowledge, the researchers were able to apply CRISPR / Cas genome editing, for example, to completely cancel the production of acetic acid or, conversely, switch to an ultra-high level of production of acetic acid, and then return everything as it was.

Such modified yeast strains are intended to be used to verify the optimal production of acetic acid for the probiotic protection of laboratory animals. This, in turn, can contribute to improved treatment of intestinal diseases.


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