Cannabinoid Synthase Orthologues for Specific CBGA Conversion

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Solution Overview

Problem

Existing methods for synthesizing cannabinoids lack specificity and yield efficiency, necessitating the development of alternative cannabinoid synthases from organisms other than Cannabis sativa.

Innovation Solution

Utilizing cannabinoid synthase orthologues from organisms such as Citrus sinensis, Brassica napus, and others, recombinantly expressed in Saccharomyces cerevisiae and Pichia pastoris, to catalyze the biosynthesis of cannabinoids from cannabigerolic acid.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If cannabinoid synthases from Cannabis sativa are used for cannabinoid biosynthesis, then the pathway can be established in heterologous systems, but the yield and specificity are insufficient

Engineering Contradiction:

Improvecannabinoid yieldVSAvoidcannabinoid synthesis specificity

Core Design Contradiction:

ProductivityVSManufacturing precision

Solution Approach 1:

The patent changes the source organism parameter of the cannabinoid synthase enzyme from Cannabis sativa to orthologous enzymes from diverse organisms including bacteria, plants, and fungi. This parameter change in enzyme source enables both high yield production and high specificity for particular cannabinoids (e.g., THCA, CBDA, CBA) that were not achieved with Cannabis sativa enzymes in heterologous systems

Inventive Principle:

Principle #35Parameter changes

2Productivity

If additional enzymes and methods are developed to improve cannabinoid synthesis specificity and yield, then production efficiency increases, but the complexity of the biosynthetic pathway increases

Engineering Contradiction:

Improvecannabinoid production efficiencyVSAvoidbiosynthetic pathway complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent employs cannabinoid synthase orthologues that exhibit multi-functionality, where a single enzyme from non-Cannabis organisms can catalyze the conversion of CBGA to multiple different cannabinoid products (THCA, CBDA, CBA, etc.) depending on the specific orthologue used. This universal approach simplifies the overall pathway design compared to using multiple specialized enzymes from Cannabis sativa

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent copies the cannabinoid synthase catalytic function from Cannabis sativa to orthologous enzymes from diverse organisms. These copied enzymes maintain the essential catalytic activity while exhibiting improved performance characteristics in heterologous expression systems, achieving both high yield and high specificity without requiring complex pathway engineering

Inventive Principle:

Principle #26Copying

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Achieves high-yield production of specific cannabinoids with molecular formulas of 358.5 g/mol, 374.5 g/mol, and 330.5 g/mol, including cannabidiolic acid and cannabielsoic acid, demonstrating enhanced productivity and specificity compared to traditional methods.

Implementation Method 1

contacting cannabigerolic acid with a cannabinoid synthase orthologue

Methodology Applied

Scientific EffectEnzymatic catalysis: Enzyme

Data Source

PatentUS12497600B2Biosynthesis of cannabinoids from cannabigerolic acid using novel cannabinoid synthases

Publication Date: 2025.12.16 NATIONAL UNIVERSITY OF SINGAPORE

AI summary

A method for producing a cannabinoid by contacting cannabigerolic acid with a cannabinoid synthase orthologue. The cannabinoid synthase orthologue is from an organism other than Cannabis sativa. Also disclosed is a recombinant cell of Saccharomyces cerevisiae or Pichia pastoris that includes in its genome a nucleic acid encoding the above cannabinoid synthase orthologue. The cannabinoid synthase orthologue is expressed in the recombinant cell in an active form.