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Image Credit: eXoZymes
When a bioactive molecule occurs in nature at trace levels, traditional extraction often means sifting through mountains of biomass for a few grams of material. This model fails when the target compound is ultra-rare, especially when hunting for non-psychoactive cannabinoid-type molecules for medicinal use that nature hides in tiny yields, mixed with the illegal and psychoactive compounds like THC. eXoZymes started from the recognition that many valuable compounds are simply inaccessible at commercial scale by petrochemical synthesis or plant extraction.
Here the spotlight falls on Cannabinoid Program Director John Billingsley, who oversees the “BioClick” enzyme-engineering initiative at eXoZymes. He puts it succinctly: “Our new BioClick approach opens the door to the biomanufacturing of rare and previously unthinkable target molecules that can be game-changers in medicine, nutrition, and other functional nutraceuticals.”
For the non-psychoactive cannabinoid world this means: being able to produce ultra rare or new‐to‐nature cannabinoids in a steel bioreactor, rather than harvesting hemp residues or performing complex chemical synthesis. The technology promises to unlock molecules that were previously simply uncommercial or inaccessible.
Enzymes × AI: Crafting the New Biomanufacturing Engine
At the heart of the company’s biomanufacturing technology is what they call “exozymes” that are enzymes bioengineered using AI and advanced lab technology to work outside of cells, in precisely controlled cascade reactions in bioreactors. eXoZymes describes how they eliminate the “cellular constraints” that traditionally limit yields and complicate scale-up.
The company built BioClick as a tool that allow thousands of enzyme variants to be screened rapidly via high-throughput mass-spec and AI-driven analytics, accelerated by what Billingsley calls “Artificial Evolution,” the next generation beyond directed evolution and rational design that is how enzymes inside of cells typically have been engineered.
In practical terms for a cannabinoid or nutraceutical developer this means that a once rare compound (or analog thereof) that might have required years and heavy cost to develop via synthetic biology or chemical synthesis can instead be brought through a DBTL (design–build–test–learn) cycle in months. One concrete milestone the company achieved was producing gram-scale quantities of a rare compound (N-trans-caffeoyltyramine, or NCT) at 96% yield and over 99% purity in only five months. NCT is a small molecule that helps boost metabolism, by turning body fat into energy.
While NCT is not a cannabinoid, the achievement shows the platform’s capability and gives a tangible analogue for what could be possible for rare cannabinoids or analogs thereof.
A Path to Commercial Scale
eXoZymes does not itself market end-products. Instead, the company licenses its exozyme platform to partners and Joint Venture companies, who bring domain expertise in a given market. eXoZymes focus on building new biosolutions for a range of high-value natural products with pharmaceutical and nutraceuticals potential.
Billingsley emphasizes the freedom that this model affords: “By building a complete tool set from enzyme engineering to pilot scale synthesis, we’re setting a new standard for what can be done with bio-based click chemistry.”
Because the platform uses scalable enzyme cascades rather than cell‐based production or heavy petrochemical steps, the company argues that it can convert over 90% of feedstock into desired end product, a level of efficiency unheard of in many prior approaches.
In the context of non-psychoactive cannabinoid nutraceuticals and pharmaceuticals, this means the business case becomes more viable. Instead of relying on extreme extraction methods from plants or daunting chemical synthesis, a company could license the exozyme route and manufacture rare cannabinoid analogs at commercial volumes, with much higher efficiency, lower cost, and less environmental impact.
Building a Toolkit That Turns Science Into Scalable Solutions
The nutraceutical and pharmaceutical potential of new-to-nature or ultra-rare cannabinoids is increasingly recognized. But extraction economics and chemical synthesis complexity have been major bottlenecks. Here eXoZymes’ platform offers a compelling alternative. Because Billingsley and his team have built the BioClick toolkit, the company is opening the door to analogs, derivatives, and entirely new small molecules previously inaccessible.
The company’s alignment with four recent Nobel Prizes in Chemistry including directed evolution (2018), CRISPR (2020), bio-orthogonal click chemistry (2022), and computational protein design (2024) underscores the scientific layering of the technology.
For a brand or business seeking to bring to market a non-psychoactive cannabinoid nutraceutical (or even pharmaceutical), partnering with a platform like eXoZymes could reduce time to market, scale risk, cost, and supply-chain constraints. And because eXoZymes is already serving North America and targeting nutraceuticals and pharma, the strategic alignment is clear.
Momentum, Milestones, and What Lies Ahead
While eXoZymes is still pre-revenue, it has achieved important milestones, including selection as a core industry partner in a major initiative to advance modular cell-free biomanufacturing. It has also launched its first spin-out subsidiary, NCTx, focused on the compound NCT.
Billingsley’s leadership in the BioClick program and his public commentary underscore the company’s ambition and technical depth. “NCT is the first of many natural products to be unlocked with exozymes,” Billingsley states, “and BioClick sets the stage for rapid development and biomanufacturing of additional pharmaceutical targets like cannabinoids.“
In short, for audiences and brands in the non-psychoactive cannabinoid space who are exploring how to reliably scale novel molecules, the story of eXoZymes and the role of Billingsley offers a compelling playbook: move beyond extraction bottlenecks, leverage enzyme cascades outside cells, optimize targets using advanced methods,, and bring new molecules to market with speed and commercial viability.