Potential Alzheimer's supplement can be produced in yeast, scientists discover
Ergothioneine is a natural amino acid with anti-oxidative properties which is said to prevent cellular stress, which can lead to brain diseases, neurological damage and cancer. In nature, ergothioneine is produced by bacteria and fungi, but the enzymes bacteria and fungi use for making ergothioneine make up slightly different pathways.
Because of today’s expensive chemical production routes, current market prices of ergothioneine are very high compared to vitamins so scientists have been working to optimise production to reach a higher yield and reduce the cost to consumers.
For the first time, in a study published in Frontiers in Bioengineering and Biotechnology, researchers from The Novo Nordisk Foundation Center for Biosustainability (DTU Biosustain) have been able to produce ergothioneine by engineering and optimising baker’s yeast.
Steven Van der Hoek, PhD Student at The Novo Nordisk Foundation Center for Biosustainability (DTU Biosustain) explains that scientists have explored the possibility of extracting ergothioneine from mushrooms but this is extremely expensive and requires mushroom farms taking up areas of potential farming land.
“By making this important antioxidant in a biobased fashion, you avoid using chemicals or farmland. Yeast is far better at producing ergothioneine than humans or mushrooms could ever be.
“The bacterial pathway in E. coli uses a lot of energy while the fungal pathway in yeast doesn’t. That could lead to a production benefit. Also, yeast is a safe and well-known production host for food supplements."
Enzymes are the key
In the study, the scientists chose to screen enzymes from different fungi and from the bacterium Mycobacterium smegmatis in various combinations to identify the clones with the highest ergothioneine production. As production host they used yeast, and they discovered that two specific enzymes NcEgt1 and CpEgt2, both fungal enzymes, made the best combination.
They also investigated potential ergothioneine transporters to increase the yield from their yeast strain. Unfortunately, this did not have any effect.
One thing that worked was to add amino acids that operate as building blocks of ergothioneine. By doing this, they were able to increase the production of ergothioneine significantly.
This increased the production to 0.6 g/L in 84 hours, which compares well with the current best-reported production in E. coli that gets 1.3 g/L in 216 hours.
Their method produced 0.6 gram of ergothioneine per liter of yeast broth in a small-scale fermentation process.
Currently, the scientists are trying to increase productivity by engineering the strain further to make a commercially viable product.
Source: Frontiers in Bioengineering and Biotechnology
Van de Hoek. S. A., et al
"Engineering the Yeast Saccharomyces cerevisiae for the Production of L-(+)-Ergothioneine"