Is yeast a cannabinoid powerhouse?

A group of scientists, led by Jay Keasling of the University of California, Berkeley, US, has modified yeast to produce the key compound that naturally occurs in Cannabis sativa, otherwise known as marijuana.

In a new paper in the journal Nature, Keasling and colleagues say the findings could lead to new ways of large-scale production of both naturally occurring and synthetic cannabinoids.

The researchers point out that cannabinoids have been approved for pharmaceutical purposes in several countries, but that the compounds themselves are not abundant, even in the cannabis plant, which hinders production.

In addition, the long history in most countries of scheduling of marijuana as an illegal substance has stifled research.

“This work lays the foundation for the large-scale fermentation of cannabinoids, independent of cannabis cultivation, which will enable the pharmacological study of these highly promising compounds and could ultimately lead to new and better medicines,” they write.

To accomplish the modification, Keasling and his colleagues introduced cannabis genes into the yeast’s metabolic pathways.

Ultimately, these changes allow the yeast to process sugar (in this case, galactose, a component of lactose) into olivetolic acid.

The yeast then processes the olivetolic acid into cannabigerolic acid, a precursor to C49-tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA).  THCA is the naturally occurring compound in marijuana. To become the active compound THC, it is decarboxylated – usually through heating.

“In summary, we engineered yeast strains capable of producing the major cannabinoids found in cannabis from galactose,” they write.

“Pending the identification of novel cannabinoid synthases, we expect to be able to produce a large fraction of this class of natural molecules.”