Papaver Plant CODM Gene Deletion for High Codeine Yield

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Solution Overview

Problem

Traditional plant breeding methods for increasing codeine content in Papaver somniferum are labor-intensive and time-consuming, and existing methods for altering alkaloid profiles in opium poppy are inefficient, as they often result in unknown genotypes and require costly chemical synthesis due to low natural codeine levels.

Innovation Solution

Deletion of one or more copies of the codeine 3-O-demethylase (CODM) genes in Papaver plants, leading to undetectable CODM activity and significantly increased codeine content, with the modified plants exhibiting at least 45% codeine in alkaloid extracts, allowing for marker-assisted selection and potentially reducing the need for chemical synthesis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If traditional plant breeding methods are used to increase codeine content, then codeine levels can be improved, but the process is labor-intensive and time-consuming

Engineering Contradiction:
Improvecodeine contentVSAvoidbreeding time
Core Design Contradiction:
Quantity of substanceVSLoss of time

Solution Approach 1:

The patent applies parameter changes by modifying the genetic composition of the plant - specifically deleting CODM genes to alter the alkaloid biosynthesis pathway. This genetic parameter change directly increases codeine content from typical low levels to high levels (≥45% of total alkaloids), resolving the contradiction by achieving rapid genetic improvement without traditional multi-generation breeding time investments

Inventive Principle:
Principle #35Parameter changes

2Adaptability or versatility

If chemical mutagenesis is used to alter alkaloid profiles, then diverse alleles can be obtained, but the screening process is laborious and time-intensive

Engineering Contradiction:
Improvealkaloid profile diversityVSAvoidscreening efficiency
Core Design Contradiction:
Adaptability or versatilityVSProductivity

Solution Approach 1:

The patent extracts and removes the specific CODM genes responsible for converting codeine to morphine. By taking out these specific genetic elements through targeted deletion, the invention achieves precise alkaloid profile modification (high codeine, low/undetectable morphine) without requiring laborious screening of numerous mutagenized plants, thus resolving the productivity contradiction

Inventive Principle:
Principle #2Taking out (Extraction)

3Quantity of substance

If CODM expression is silenced to increase codeine content, then codeine levels can be improved, but the genotype remains unknown and requires further characterization

Engineering Contradiction:
Improvecodeine contentVSAvoidgenotype information
Core Design Contradiction:
Quantity of substanceVSLoss of information

Solution Approach 1:

Instead of using gene silencing techniques that obscure the genetic modification, the patent inverts the approach by directly deleting the CODM genes. This inversion provides complete genotype information - the plants have known deletions in specific CODM gene copies - while achieving the desired high codeine phenotype, thus resolving the information loss contradiction

Inventive Principle:
Principle #13The other way round (Inversion)

4Quantity of substance

If natural codeine extraction is used, then codeine can be obtained, but the levels are typically less than 5% of morphine levels requiring costly chemical synthesis

Engineering Contradiction:
Improvecodeine contentVSAvoidproduction cost
Core Design Contradiction:
Quantity of substanceVSEase of manufacture

Solution Approach 1:

The patent fundamentally changes the biosynthetic parameter by deleting CODM genes, which shifts the alkaloid accumulation pattern. This results in codeine becoming the dominant alkaloid (≥45% of total) rather than a minor component (<5% of morphine), making direct extraction economically viable and eliminating the need for costly semisynthetic conversion processes

Inventive Principle:
Principle #35Parameter changes

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 approach enables the efficient production of high-codeine Papaver plants with predictable alkaloid profiles, facilitating marker-assisted breeding and potentially reducing the reliance on costly chemical synthesis by achieving high codeine content through genetic modification.

Implementation Method 1

thebaine is transformed to codeine, which is, through the activity of the CODM, converted to morphine by de-methylation

Methodology Applied
Scientific EffectEnzymatic demethylation: Enzyme

Data Source

PatentEP3358941B1Modified plant
Publication Date: 2024.12.11 SUN PHARMACEUITCAL INDUSTRIES (AUSTRALIA) PTY LTD
  • EP3358941B1 patent drawingFigure 1A~1B
  • EP3358941B1 patent drawingFigure 1C~1D
  • EP3358941B1 patent drawingFigure 1E~1F

AI summary

The disclosure relates to modified plants of the genus Papaver comprising two or more genes encoding codeine (O)-demethylase (CODM) wherein the modified plants have modified alkaloid content when compared to unmodified plants wherein the alkaloid content has a high codeine phenotype.