Danish scientists have introduced baking yeast (Saccharomyces cerevisiae) genes of enzymes, which ensure the synthesis of psilocybin, reported in Metabolic Engineering. Genes were functional in the new body and helped to produce the desired alkaloid. In this modified yeast did not need to add in a nutrient medium of the intermediate products of its synthesis, such as 4-hydroxyindole.
Psilocybin is an alkaloid mushrooms of the genus Psilocybe , and some others. Because it has a hallucinogenic effect, in many countries it is forbidden to use. However, in recent years, psilocybin found a strong antidepressant properties. He also lowered anxiety in cancer patients and did not cause serious side effects. Currently, a series of clinical trials to assess its ability to reduce the craving for alcohol.
If the substance is proved efficient and safe, its status can be reviewed and begin using it to treat the described condition. Then you will need to obtain it in large enough quantities. To extract psilocybin from Psilocybe is very expensive: its mass is 0.2–1 percent of the total dry weight of the fungus. So it makes sense to “teach” other organisms to produce this substance in large quantities. It is better to choose those that are already used in biotechnology.
For this model organisms need to be able to synthesize the enzymes that support the synthesis of psilocybin predecessors. This is a multi-step process — for each reaction requires its own enzyme, and it or its gene, can not work outside the cells of fungi. This problem arose when psilocybin is “taught” to make E. coli (Escherichia coli). Then it turned out that the mushroom the catalyst is one of the most important reactions in the chain joining the hydroxyl group to the fourth carbon atom of the indole ring is not functioning. Therefore, in a nutrient medium the bacteria had to add 4-hydroxyindole.
Staff at the Danish technical University, headed by Irina Borodina (Irina Borodina) introduced the genes of the enzymes necessary for synthesis of psilocybin from glucose, closer Psilocybe organism — Baker’s yeast. It is also a fungus. All the right genes, with the sole exception was received from the Psilocybe cubensis. Among them was the gene for the enzyme catalyzing the hydroxylation of the indole ring.
Yeast were able to synthesize all the necessary enzymes and therefore psilocybin. In contrast to E. coli, in nutrient broth yeast didn’t need to add unusual substance: raw material for the production of the alkaloid served glucose. The maximum yield of psilocybin amounted to 627 milligrams per liter of yeast culture. Also, mushrooms are produced decay product of psilocybin — psilocin in concentrations up to 580 milligrams per liter. In addition it was found that the modified yeast produces other tryptamines, in particular, baeocystin, norbaeocystin and aeruginascin. At the same time, which is pretty important in the culture of the yeast did not accumulate ethanol.
This is not the first case when the other is synthesized psilocybin mushrooms, which normally is not able to do it. Previously, researchers from University of Jena (Germany) achieved the expression of genesthat provide education relevant alkaloid breeding of Aspergillus (Aspergillus nidulans). Although this fungus is widely distributed, techniques of cultivation of yeast are better developed, so that to extract the alkaloid from S. cerevisiae to be profitable.
The work is interesting because it is an example of the operation of “designer enzymes” in synthetic biology. If you choose the right combination of biological catalysts and to introduce them into cells of some model organism, it is possible in theory to not only the already known substances but also those which do not occur in nature. Considering how much there is of indole derivatives and how the various functions they perform, build systems for their synthesis will be useful not only psychopharmacology, but also for the production of drugs another profile and also for agronomy, perfumery and many other industries.
Baker’s yeast — a classic object of biotechnology. The number of substances that have learned to synthesize with them, is enormous. Among them morphine, various cannabinoids, noscapine (alkaloid to help with the cough and probably cancer), geraniol and linalool (give the beer a distinctive taste and smell).