Briefly, InMed has identified the specific gene sequences from the cannabis plant that encode the instructions to make specific enzymes that enable cannabinoid assembly and subsequently transplanted these genes into the bacterium E. coli. This intervention converts the bacterium into a manufacturing engine that produces large quantities of the target compound on demand.

This development provides an opportunity for industrial-scale manufacturing of naturally occurring cannabinoids, and we believe that it is a significant improvement over existing manufacturing platforms such as direct extraction from cannabis plants.

Direct extraction of minor cannabinoids is quite cumbersome, time-consuming and low yielding. The use of microorganisms for manufacturing cannabinoids eliminates the process of planting, growing, harvesting, extracting and purifying. There are also economic and environmental savings such as substantially reduced resource requirements (water, electricity, manpower, etc.). Furthermore, the growing process has several hard-to-remove impurities (e.g., pesticides), potentially presenting significant safety issues. As with all crops, yield fluctuations present an additional risk. Only a few of the 100+ cannabinoids can be extracted from the plant in sufficient quantities to make that process economically viable.

Cannabinoids are prenylated polyketides that are derived from fatty acid and terpenoid precursors. The biosynthesis of these molecules involves four metabolic pathways, two of which originate from central carbon metabolism. The first pathway (“terpenoid pathway”) culminates with the synthesis of geranyl pyrophosphate (“GPP”), and neryl pyrophosphate (“NPP”). These molecules are terpenoid building blocks, or precursors.

The second cannabinoid biosynthetic pathway, the “polyketide pathway”, is a truncated version of a polyketide biosynthetic pathway and results in the second requisite precursor, either: olivetolic acid (“OA”) and/or divarinic acid (“DVA”). The polyketide precursors subsequently combine with the terpenoid precursors in the third pathway, which comprises a single, specialized gateway enzyme, to yield the gateway cannabinoids. For instance, OA combines with GPP to yield the gateway cannabinoid cannabigerolic acid (“CBGA”).

Synthesis of the gateway cannabinoid CBGA is the most prevalent pathway in the cannabis plant, leading to high levels of both THC and CBD. InMed’s technology can mimic the natural synthesis of cannabinoids using an E. coli fermentation process.

The gateway cannabinoids are subsequently modified in the fourth pathway to yield cannabinoids such as tetrahydrocannabinolic acid (“THCA”) and cannabidiolic acid (“CBDA”). We refer to the fourth pathway as the downstream pathway and it involves the transformation of the acid form of the cannabinoids into the non-acid form via enzymes called “synthases”. Other combinations of the various precursors result in different gateway cannabinoids which, in turn, leads to diversification into the 100+ cannabinoids.

Earlier research for InMed’s bioprocesses employed E. coli and S. cerevisiae as the production hosts. Our advanced investigations have identified E. coli as a superior host for production of cannabinoids.