2020-172 MICROBIAL PRODUCTION OF CANNABINOID PRECURSOR OLIVETOLIC ACID AND ITS ANALOGUES

UCLA researchers in the Department of Chemical & Biomolecular Engineering have developed a novel method for the production of cannabinoid precursor olivetolic acid for the scalable synthesis of cannabinoids.

BACKGROUND:

Cannabinoids, the chemicals found in the cannabis plant, are widely recognized for their medical applications to alleviate pain. Particular cannabinoid formulations have been approved as prescription drugs for the treatment of various aliments plaguing patients, including nausea and vomiting associated with cancer chemotherapy as well as anorexia and cachexia related to HIV/AIDS. Although cannabinoids have significant benefits in human health, low abundance in the native plant and legal regulations surrounding Cannabis has prevented studies of additional medical applications of these compounds. In particular, the large scale chemical synthesis of cannabinoids has remained elusive due to the complex chemical structures of cannabinoids. There is an unmet need for a sustainable strategy to synthesize cannabinoids at high titers.

INNOVATION:

Scientists at UCLA have established a method for the synthesis of olivetolic acid and its analogues with high yields, using fungal biosynthetic machinery. Olivetolic acid is a central intermediate that links simple building blocks to form intricate late-stage compounds during microbial fermentation of cannabinoids. In contrast to previous methods of olivetolic acid synthesis, this in situ synthetic process does not rely on the collaboration of tetraketide synthase and olivetolic acid cyclase enzymes, and does not require a constant supply of hexanoyl-CoA precursor. Olivetolic acid synthesis from this method is scalable and produces products with a total titer of >100 mg/L. This technology has a variety of applications in the field of pain management, ranging from nausea and vomiting associated with cancer chemotherapy to anorexia and cachexia related to HIV/AIDS.

POTENTIAL APPLICATIONS:

•Generation of cannabinoid precursors

•Prescription drugs to treat a variety of ailments

ADVANTAGES:

•Large scale cannabinoid synthesis (total titer of  >100 mg/L)

•Uses synthetic process that already exists in nature

•Avoids IP restrictions on olivetolic acid synthase and olivetolic acid cyclase enzymes

•Does not rely on a constant supply of the cannabinoid precursor hexanoyl-CoA

DEVELOPMENT-TO-DATE:

This synthesis method has been validated by the synthesis of water-soluble β-amino acid type polymers and soluble poly(acetylene) derivatives.

Patent Information:
For More Information:
Earl Weinstein
Associate Director of Business Development
eweinstein@tdg.ucla.edu
Inventors:
Yi Tang