Recombinant Yeast Cannabinoid Biosynthesis for Selective Production

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

The production of cannabinoids from Cannabis sativa is hindered by legal and social issues related to psychoactive components, lack of selectivity in cannabinoid production, high energy consumption, and environmental unsustainability, limiting the availability of minor cannabinoids for research and therapeutic use.

Innovation Solution

A recombinant Saccharomyces cerevisiae cell is engineered with a cannabinoid biosynthetic pathway using non-Cannabis sativa genes, expressing enzymes like CoA ligases, malonyl-CoA synthetase, olivetol synthase, and olivetolic acid cyclase, to produce cannabinoids from precursor substrates, allowing for controlled synthesis of specific and novel cannabinoids.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If cannabinoids are produced from Cannabis sativa extracts, then cannabinoids are available for use, but legal and social issues arise due to psychoactive components and lack of selectivity

Engineering Contradiction:

Improvecannabinoid availabilityVSAvoidlegal and social issues

Core Design Contradiction:

Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent extracts the cannabinoid biosynthetic pathway genes from Cannabis sativa and transfers them into a heterologous host organism (E. coli or yeast). This separates the desirable cannabinoid production capability from the harmful psychoactive components and legal issues associated with the source plant, allowing selective production of specific cannabinoids without producing the full spectrum of plant compounds.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses heterologous host organisms (E. coli or yeast) as intermediary systems to produce cannabinoids. These intermediaries express cannabinoid biosynthetic pathway enzymes when provided with appropriate precursor substrates, enabling controlled production of specific cannabinoids without directly cultivating Cannabis sativa, thus avoiding legal and social complications.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Quantity of substance

If Cannabis sativa is cultivated to produce cannabinoids, then cannabinoids are obtained, but energy consumption is high and environmental sustainability is compromised

Engineering Contradiction:

Improvecannabinoid productionVSAvoidenergy consumption

Core Design Contradiction:

Quantity of substanceVSUse of energy by moving object

Solution Approach 1:

The patent replaces the complex mechanical and environmental control systems required for Cannabis sativa cultivation (climate control, irrigation, harvesting, extraction facilities) with a simplified microbial fermentation system. The heterologous hosts can be cultured in controlled bioreactors using standard fermentation processes, dramatically reducing energy consumption and environmental impact while maintaining cannabinoid production.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Adaptability or versatility

If Cannabis sativa is cultivated to produce cannabinoids, then cannabinoids are obtained, but there is limited control in the selectivity of cannabinoids produced

Engineering Contradiction:

Improvecannabinoid selectivityVSAvoidproduction control

Core Design Contradiction:

Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The patent introduces specific cannabinoid biosynthetic pathway gene combinations into the heterologous host, enabling localized production of specific cannabinoid types. By selecting which pathway genes to express (e.g., THCA synthase, CBDA synthase, or other cannabinoid synthases) and providing appropriate precursor substrates, the system achieves precise control over which cannabinoids are produced, rather than producing the mixed profile from whole plant extraction.

Inventive Principle:

Principle #3Local quality

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

This approach enables the production of specific and novel cannabinoids with high yield, bypassing the limitations of traditional cultivation, facilitating research and therapeutic applications while reducing environmental impact.

Implementation Method 1

Methodology Applied

Scientific EffectEnzyme catalysis: Enzyme

Data Source

PatentUS12497636B2Recombinant <i>Saccharomyces cerevisiae </i>cells for cannabinoid production

Publication Date: 2025.12.16 NATIONAL UNIVERSITY OF SINGAPORE

AI summary

A recombinant cell of Saccharomyces cerevisiae that includes in its genome nucleic acids encoding cannabinoid biosynthetic pathway genes. A cannabinoid is produced by the recombinant cell in the presence of a cannabinoid precursor substrate and at least one of the cannabinoid biosynthetic pathway genes is from an organism other than Cannabis sativa, wherein the at least one of the cannabinoid biosynthetic pathway genes encodes a prenyltransferase. In an embodiment, the prenyltransferase is NphB from Streptomyces sp. having the amino acid sequence of any one of SEQ ID NOs: 8-11. Also disclosed is a method for producing a cannabinoid with the recombinant cell and the cannabinoid precursor substrate.