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The future of cannabinoid production. Cannabis bioengineering
Cannabis is an exciting area of
Cannabis (marijuana) is the most popular illicit drug in the world. As a result, it has become a big industry. In the United States, an increasing number of states have legalized cannabis for medical and recreational purposes. Supply cannot keep up with demand and cannabis is one of the most profitable crops in the United States. However, manufacturing active ingredients on an industrial scale remains challenging because the plant has a very low yield of bioactive components.
Cannabis plants synthesize hundreds of chemicals known as cannabinoids which are used for medical and recreational purposes. The two most common molecules are tetrahydrocannabinol (THC) and cannabidiol (CBD), which are pharmacologically distinct, with THC producing distinctive psychoactive effects and CBD showing the potential to treat seizures and many other conditions.
Cannabis is the only plant known for the production of tetrahydrocannabinol (THC), but it is a plant therefore it is not possible to define it suitable for the production of the chemical molecule on an industrial scale, as it is normally found only on the flowering tops of the plant known as trichomes, which means that the remainder of the cannabis plant cannot be used for this purpose.
The last two millennia have seen the use of cannabis increase greatly, and this has led to the widespread cultivation of the plant all over the world. Although the demand for the active ingredients is high, current extraction and isolation methods are expensive, sometimes inefficient and not very environmentally friendly. Discovering previously unknown new cannabinoids is also challenging, as it relies on the chance discovery of molecules in plants out of the billions that potentially exist. However, advances in genetic manipulation technologies and synthetic biology allow us to alter production pathways in a subtle way. This level of control would not be possible through traditional cultivation techniques, which require several generations and tens of years to produce results at a great cost to both humans and natural resources.
Cannabis Genetic engineering
Genetic engineering, on the other hand, could provide much more efficient alternatives. Researchers and biotechnology companies aspire to replace cannabis plants with microorganisms that have been genetically enhanced to produce the well-known psychoactive molecule THC, cannabidiol (CBD) and a multitude of other pharmacologically interesting minor cannabinoids. Others aim to modify the chemical synthesis in the cannabis plant by genetically altering its cells to create the desired molecules from the flowering tops, thereby increasing their yield.
In both cases, the goal remains the same: to produce cannabinoids more economically, efficiently and reliably than conventional plant cultivation in greenhouses or in the open field. Additional benefits of microbial synthesis include the ability to mass produce rare cannabinoids which are usually present in plants only in small percentages. Transgenic plants can also be engineered to have superior resistance to pests and environmental stresses.
Cannabinoids Commercial interest
Commercial interest in this kind of strategy is growing. Genetic engineering is capable of bringing normal agricultural practices in use for centuries into the age of biotechnology, resulting in changes that would be felt throughout the cannabis world. In the production of cannabis extracts and its pure molecules, plants could be supplanted by microbes and a wider range of cannabinoids could become available for use in medical and recreational products.
If this happened, the iconic cannabis leaf would no longer represent the source of origin of the active ingredients. In its place it would be supplanted by a simple stainless steel bioreactor which could be more suitable for the purpose, even reducing enormously the costs.
Bioproduction would also offer the advantage of being able to produce cannabinoids, excluding all risks associated with agriculture such as bad weather, parasites and other environmental uncertainties. Production in the laboratory would also be better for the environment because less energy would be used, as a bioreactor consumes less energy than growing indoor cannabis.
Probably another great advantage derived from the use of biosynthesis platforms would be precisely that of obtaining abundant quantities of minor cannabinoids that are usually found only in trace amounts in cannabis plants, at a very low cost.
Many companies are working to try to produce cannabinoids through the use of yeast, bacteria or algae. By tweaking some yeast genes and injecting others from bacteria and the cannabis plant, one company has created an organism that can perform all the chemical reactions involved in cannabinoid production. They found that it is possible to feed simple sugar yeast by generating low amounts of inactive THC or CBD, which can then be converted to their active forms by heating. It would also be possible to create entirely new cannabis molecules that could be better therapeutics. However, getting something to work in the lab does not guarantee the same success in a manufacturing plant. Turning yeast into miniature cannabinoid factories poses considerable challenges.
Some researchers are trying to address this by fielding alternative organisms such as bacteria. An advantage of bacteria over other cell systems is that they do not attach sugars to proteins they produce in the same way as yeast and other organisms with a closed core. Bacteria also naturally secrete cannabinoids from which they can be easily extracted. This method would offer many advantages in terms of production speed and cost because it would allow for continued production, while organisms that retain their chemical richness within cells must be “cracked” open as part of a batch production system. A further problem in the use of yeast for the production of cannabinoids derives from the fact that these molecules have evolved in plants as a defense mechanism against insects, microorganisms and other biological threats. This means that the chemicals researchers desire are often deadly to the organisms that were designed to produce them.
In addition to the biological benefits, cannabinoid production in an unconventional organism such as a seaweed would be very interesting.
Rather than trying to force the production of cannabinoids in microorganisms, some companies remain steadfast in cannabis plants, using biotechnological tools to boost the crop.
Cannabinoids genetically modify
It seems it is possible to genetically modify cannabis to allow it to produce cannabinoids throughout the plant and not just in the flowers and trichomes, to increase the yield provided by each plant.
Cannabis specialists have filed patents covering methods of manipulating the synthesis of cannabinoids in plants, in such a way as to generate cannabis plants that only produce CBD or only CBG.
Some skilled cannabis growers have instead created plants rich in minor cannabinoids such as CBG or THCV through selective genetic selection. Modification through genetic engineering is probably the simplest way to achieve a desired phenotype. Genetic engineering is also a powerful tool for probing the function of cannabis genes, information that can then be fed back into a conventional breeding program.
Cannabis bioengineering is underway. Researchers are genetically modifying plants to produce more cannabinoids and alter their growth cycles, with the potential for large-scale industrial production.
One obstacle remains the shyness of consumers regarding genetically modified crops, which could lead to a distrust of biosynthesis based on microorganisms.
People like their weed and will worry if their cannabinoids come from a genetically modified yeast or a field grown plant.
On the other hand, the technological provenance of cannabinoids may not be as important for the pharmaceutical sector, where consumers tend to be less opposed to genetic engineering, even though biochemical-derived cannabinoids will probably never match the botanical synergy of the hundreds of molecules they contain. found in cannabis.
Benefits and limitations of genetically modified cannabis
It is important to know the benefits and limitations of genetically modified cannabis to better understand its possibilities. Genetic engineering could provide more efficient alternatives, but would it be better for patients who purchase marijuana for medical purposes? Would it be beneficial to grow this plant or would it be better to get cannabinoids from other sources?
Proponents of cannabis biotechnology say the plant is often inefficient at producing the molecules of greatest interest to drug companies and researchers. Genetic modification could allow for the industrial-scale production of cannabinoids that have pharmaceutical potential but are found at low levels in cannabis, such as THCV (tetrahydrocannabivarin) or cannabigerol (CBG). Genetic engineering could also provide more efficient alternatives to the extraction techniques currently in use, and put an end to concerns of contamination with fungi, bacteria or pesticides.