UCLA researchers in the department of Chemical and Biomolecular Engineering have developed a microbial de novo biosynthesis platform that enables scalable production of rare cannabinoids with enhanced receptor affinity from simple sugar feedstocks.
BACKGROUND: Cannabinoids are bioactive natural products that interact with the human endocannabinoid system and have demonstrated therapeutic potential across indications such as pain, epilepsy, and cancer-related symptoms. While major cannabinoids such as Δ9–THC and CBD are readily derived from the Cannabis plant, rare cannabinoid analogs with modified alkyl chains have been shown to exhibit significantly enhanced potency and biological activity, some of which can display even stronger affinity toward human CB1 receptors than Δ9–THC.
However, these rare cannabinoids are present at extremely low levels in plant sources, often below 1 mg/g, making large-scale extraction impractical. Synthetic chemistry approaches are similarly constrained by multi-step complexity and poor scalability. As a result, there is a clear need for alternative production platforms capable of generating rare and novel cannabinoids at scale.
INNOVATION: Researchers at UCLA, led by Dr. Ike Okorafor, have engineered a novel single-celled fungal host capable of biosynthesizing two rare cannabinoids from simple sugars.
This platform integrates fungal biosynthetic pathways with plant-derived enzymes to enable de novo production of rare cannabinoid precursors at measurable titers under optimized conditions. These compounds can be further converted into highly potent derivatives demonstrating up to ~30-fold greater receptor binding affinity compared to conventional cannabinoids.
Compared to natural plant extraction yields (~0.13 mg/g for analogous compounds), this approach enables scalable, fermentation-based production from inexpensive feedstocks, significantly improving accessibility to these molecules. The system is modular and extensible, allowing incorporation of diverse biosynthetic gene clusters to generate additional rare or novel cannabinoid analogs.
POTENTIAL APPLICATIONS:
ADVANTAGES:
DEVELOPMENT-TO-DATE: The platform has been validated through in vivo production of multiple rare cannabinoids, with demonstrated pathway optimization and successful downstream conversion to active compounds.
Related Papers (from the inventors only):
Yan C, Okorafor IC, Johnson CW, Houk KN, Garg NK, Tang Y. Microbial biosynthesis of rare cannabinoids. J Ind Microbiol Biotechnol. 2024 Dec 31;52:kuaf013. doi: 10.1093/jimb/kuaf013. PMID: 40359163; PMCID: PMC12134893.
Keywords: THC, CBD, CB1, Cannabinoids, Cannabis, De novo synthesis, biosynthesis, marijuana, chemical synthesis