Genetically Modified Yeast for High-Yield CBDa Biosynthesis

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Solution Overview

Problem

The production of cannabinoids, such as cannabidiolic acid (CBDa), in preparative amounts and high yield has been challenging due to inefficiencies in existing methods.

Innovation Solution

Genetically modified yeast cells are engineered to express enzymes of the cannabinoid biosynthetic pathway, including acyl-activating enzyme, tetraketide synthase, cannabigerolic acid synthase, and CBDa synthase, allowing for biochemical synthesis and high-yield production of CBDa.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If traditional cannabinoid production methods are used, then production is possible, but yield and efficiency are low

Engineering Contradiction:
Improvecannabinoid production yieldVSAvoidproduction complexity
Core Design Contradiction:
ProductivityVSEase of manufacture

Solution Approach 1:

The patent uses yeast cells as a living factory intermediary to produce cannabinoids. The yeast is genetically modified to express plant-derived enzymes (AAE, TKS, CBGaS, CBDaS) that catalyze the biosynthetic pathway from terpenoid precursors to CBDa, thereby mediating the transformation from simple chemical precursors to complex cannabinoid products with high efficiency and selectivity

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent optimizes multiple parameters including enzyme expression levels, culture conditions (temperature, pH, aeration), precursor concentrations, and induction timing to maximize CBDa yield. The two-stage fermentation process with controlled induction at specific optical density values represents parameter optimization to achieve high productivity while maintaining ease of manufacture

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If high-yield cannabinoid production is pursued, then preparative amounts can be obtained, but production efficiency decreases

Engineering Contradiction:
Improvecannabinoid amountVSAvoidproduction efficiency
Core Design Contradiction:
Quantity of substanceVSProductivity

Solution Approach 1:

The patent employs a two-stage fermentation process with periodic induction. The first stage involves growth of yeast cells to a specific optical density, followed by induction of enzyme expression. After a production phase, a second induction can be applied. This periodic action allows the system to accumulate biomass first, then efficiently convert precursors to CBDa, achieving both high quantity and high productivity

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The yeast cells are pre-cultured and conditioned before induction, allowing optimal biomass accumulation and metabolic preparation. The precursors are also prepared and added at optimized concentrations before the induction phase, ensuring that when enzyme expression is induced, the system is primed for maximum efficient production of large quantities of CBDa

Inventive Principle:
Principle #10Preliminary action

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

The method enables efficient and selective production of CBDa, overcoming previous challenges by utilizing genetically modified yeast cells to express specific enzymes, resulting in improved yield and purity.

Implementation Method 1

the host cell may be modified to express one or more enzymes of a cannabinoid biosynthetic pathway, such as an acyl-activating enzyme (AAE), a tetraketide synthase (TKS), a cannabigerolic acid synthase (CBGaS), a geranyl pyrophosphate (GPP) synthase, and/or a CBDa synthase (CBDaS)

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Data Source

PatentUS20240344093A1High efficiency production of cannabidiolic acid
Publication Date: 2024.10.17 AMYRIS INC
  • US20240344093A1 patent drawing
  • US20240344093A1 patent drawing
  • US20240344093A1 patent drawing

AI summary

The present disclosure features compositions and methods for producing one or more cannabinoids, such as cannabidiolic acid (CBDa), in a host cell, such as a yeast cell, that is genetically modified to express the enzymes of a cannabinoid biosynthetic pathway. Using the compositions and methods of the present invention, the host cell may be genetically modified to express one or more enzymes of a cannabinoid biosynthetic pathway, such as an enzyme having CBDa synthase (CBDaS) activity.