Scientists Find a Way to Manufacture D-Lysergic Acid on an Industrial Level

Researchers in Singapore and the UK have succeeded in recreating a molecule used to treat Parkinson’s and Alzheimer’s using baker’s yeast.

Baker's Yeast

Baker’s Yeast. Image Credit Bob Blaylock

Ergot alkaloids are a class of natural products known for their usefulness in the treatment of Parkinson’s and Alzheimer’s, but also for the treatment of other neurological diseases such as migraines. “Their synthesis by chemical and biological processes is therefore of industrial interest to pharma, but so far has been encountering several difficulties,” emphasize the authors of this study published in Nature Communications.

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These drugs are produced from extracts of the ergot fungus, a parasite that develops in cereal fields (wheat, rye).

However, the production of these compounds is limited because their manufacturing processes are linked to industrial agriculture, which is affected by climate change and is criticized for its carbon impact.

Reconstituting the ergot alkaloid pathway in a strain highly adapted to liquid fermentation could potentially solve these problems, according to researchers from the Yong Loo Lin School of Medicine at the National University of Singapore and Imperial College (London, UK).

A method that could lead to industrial level production

The study focused on the main therapeutic molecule in rye ergot, called D-lysergic acid (DLA). To reduce the use of arable land to produce this drug, the researchers tested an alternative method of producing DLA.

In their experiments, they used derivatives of ergoline (a chemical compound of several alkaloids) from baker’s yeast, one of the first cellular organisms whose genome has been altered.

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Using the same fermentation process used to make beer and bread, these modified fungal cells could then eat sugar to produce DLA.

According to the researchers, although the quantities produced in the study were small, the method could be scaled up to industrial levels, allowing the yeast to produce tons of the compound each year. “Our work demonstrates proof-of-concept for the biological production of ergoline-derived compounds from sugars in a modified yeast chassis,” the researchers say.

According to statistics, between 10 and 15 tons of DLA need to be produced each year to meet the global demand for drugs made from this molecule.

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Reconstituting the complete biosynthesis of D-lysergic acid in yeast

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