Synthetic biology boffins at Berkeley have taken their research to new highs by rigging up yeast so it produces cannabis compounds – not beer.
The group, led by Jay Keasling at the University of California, Berkeley, tweaked brewers' yeast, Saccharomyces cerevisiae, so it makes both the mind-altering and vanilla – er, we mean medicinal – cannabinoids found in marijuana.
These are cannabidiol, which has been gaining traction for its potential medicinal uses, such as in tackling anxiety and pain-relief, and the psychoactive THC.
But it's no easy feat for scientists to dig into the effects because the chemicals occur in such small amounts naturally, so it's hard to extract enough to study in detail. Growing marijuana is also an incredibly intensive, expensive and environmentally unfriendly process that needs lots of heat, light and water.
That means academics are on the lookout for cheap, pure sources of the cannabinoids. Yeast seemed like a good option because its metabolic pathways have been hijacked before to produce other chemicals, like insulin, anti-malaria drugs and blood-clotting factors. It's also more environmentally friendly to boot.
The boffins used a process that stuffs different genes into the yeast to co-opt its metabolism so that instead of turning sugar into alcohol, it converts it into other chemicals.
In the case of this research, published this week in Nature, the sugar – galactose – is converted first into cannabigerolic acid (CBGA), which is described as the "mother of all cannabinoids", and then into other cannabinoids.
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Although some of the steps in this cannabinoid factory line have been reported before, this work is the first time it's been done in one go, in one cell.
The team modified a number of the yeast genes, and inserted more than a dozen genes from bacteria and marijuana. These produce enzymes that work in a chain reaction that eventually converts sugar into cannabinoids.
However, during the work, the researchers found that one of the enzymes that performs a crucial step in this process didn't work in yeast, so they went back to marijuana and isolated a previously unknown enzyme and stuck that in the yeast.
"It worked like gangbusters," said Keasling.
After that, their yeast could produce CBGA, which was converted into THCA and CBDA with the addition of more enzymes.
When these derivatives are exposed to light and heat they are converted into the active forms the researchers were after: THC, the main psychoactive compound in cannabis, and the non-mind bending cannabidiol.
They also added in enzymes that produced two natural cannabinoids that aren't well understood – CBDV (cannabidivarin) and THCV (tetrahydrocannabivarin).
But the team didn't stop there; they realised that the enzymatic steps involved in making the CBGA were flexible, so they tried out different starter chemicals in the place of the one the marijuana plant used. This generates cannabinoids that don't exist in nature, offering up more targets for medical research.
Keasling founded a company called Demtrix in 2015, and it licensed the technology to use yeast fermentation to produce cannabinoids.
"The economics look really good," Keasling said in a canned statement. "The cost is competitive or better than that for the plant-derived cannabinoids. And manufacturers don't have to worry about contamination – for example, THC in CBD – that would make you high."
Of course, the work focuses on the medical potential, emphasising the importance of a cheaper, cleaner and greener way of producing compounds for drug development. But El Reg eagerly awaits the next step in home brewing. ®