Yeast-based cannabinoid production.
The endocannabinoid system (ECS) has been shown to be an important physiological system that has the ability to finely control the brain’s immune response, and there is growing excitement about the potential of the ECS in treating neurodegenerative diseases. The ECS is a powerful physiological signaling system involved in a wide range of biological processes including sleep; basic metabolism; pain; neurological, cardiovascular, and gastrointestinal disorders; respiratory functions; reproduction; cell proliferation; and cancer. As we know it today, the ECS consists of receptors (CB1 and CB2), ligands that bind these receptors (e.g. anandamide and 2-arachidonoylglycerol), and the enzymes responsible for ligand production and degradation. The CB1 receptor is the one of most abundant GPCRs in the brain and CB2 receptor expression is greatly increased in microglia and astrocytes during neuroinflammation. Endocannabinoid signaling is increased in many animal models of neurodegenerative diseases including models of PD, AD, MS and Huntington’s disease.
Librede has engineered yeast with selected portions of the metabolic pathways of Cannabis sativa. By using only selected portions of the Cannabis metabolic pathways to produce specific cannabinoids, issues of separation and purification are greatly minimized in comparison to plant-based production. It is a low cost, efficient means of producing high purity pharmaceutical compounds and precursors targeting the ECS.
By developing yeast based cannabinoid production platform we have created an environmentally sustainable platform for the production of cannabinoids. Agricultural based production of cannabinoids requires large areas of land to be modified for plant production. In addition to removing native plants from the environment, agricultural based production requires the use of fertilizers, pesticides and large amount of water. Librede’s yeast based platform is a highly efficient system where we can recycle the water that we use and the main feedstock is sugar. We have lower energy profiles than agricultural production and we do not use any fertilizers or pesticides.
Librede’s platfrom can synthesize a variety of cannabinoids simply by substituting different enzymes into the yeast. In addition, our pathway used olivetolic acid as an intermediate, but if divarinic acid is used, the same enzymes result in cannabidivarinic acid (CBDVA) and analogous molecules. The carboxylic acid group of any of the acidic cannabinoid forms can be removed chemically or with heat, resulting in CBD, CBC, CBDV, etc. and therefore we may obtain multiple cannabinoids in a straightforward manner.
Our platform is not limited to the production of natural cannabinoids from C. sativa or other cannabis species. In addition to production of natural molecules, it is also possible to create cannabinoid-like derivatives that are pharmaceutically active, new molecular entities (NMEs). This can allow chemists to better understand how cannabinoids are made and how their modification can affect binding to ECS receptors. These insights can be used to design new cannabinoid-like molecules for therapeutic effects.
By engineering additional enzymatic pathways or mutating the enzymes present in the current pathways, we are able to make compounds derived from existing cannabinoids with novel therapeutic activities and benefits. Therefore we see our innovation as both a production platform that can be scaled for pharmaceutical production but also as a drug discovery tool that can be used to create new compounds. Our platform can take cannabinoid-like molecules from initial discovery all the way to commercial products, eliminating many of the shortcomings associated with natural product drug development.
Librede has developed strains of yeast that contain various compounds that are involved in the production of cannabinoids. These compounds can be used as building blocks for novel therapeutics or as products themselves.
Contact Librede for additional information about licensing or partnering in order to gain access to these strains.