Dominant Negative KRPI Mutants for Crop Yield Enhancement

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Solution Overview

Problem

Current methods for modifying crop characteristics, such as increasing crop yields or seed size, are limited by the inefficiencies of post-transcriptional gene silencing technologies and the lack of commercially available transgenic crops with enhanced yield or seed size.

Innovation Solution

Development of variant plant cyclin-dependent kinase inhibitor (CKI) polypeptides with modified binding affinity for CDK proteins, which act as dominant negative antagonists to wild-type CKI function, allowing for accelerated cell cycle progression and increased cell proliferation when expressed in plants.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If post-transcriptional gene silencing (PTGS) is used to modify crop characteristics, then gene expression can be suppressed, but the efficiency is low and the technology is transient

Engineering Contradiction:
Improvegene silencing efficiencyVSAvoidsilencing duration
Core Design Contradiction:
ReliabilityVSDuration of action of stationary object

Solution Approach 1:

Instead of using PTGS to suppress gene expression (the conventional approach), the patent inverts the strategy by using dominant negative mutants that actively interfere with protein function. The mutant KRPI protein binds to cyclin-CDK complexes and prevents their activity, achieving more reliable and lasting effects than PTGS.

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

Solution Approach 2:

The patent modifies the protein function by changing the amino acid sequence parameters of the KRPI protein. Specific amino acid substitutions (e.g., at positions 151, 153, 149, 164, 165) create dominant negative variants with altered binding affinity and functional properties, enabling more effective and stable gene modification.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If wild-type CKI proteins are expressed to inhibit CDK activity, then cell cycle progression is slowed, but crop yield and seed size are reduced

Engineering Contradiction:
ImproveCDK inhibition effectivenessVSAvoidcrop yield
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent applies local quality by creating KRPI variants with specific modifications only in the CDK binding region (amino acid positions 151, 153, 149, 164, 165), while maintaining the rest of the protein structure intact. This localized modification allows the protein to bind cyclin-CDK complexes with high affinity but prevents effective inhibition, thereby promoting cell cycle progression and increasing crop yield.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

Instead of using wild-type CKI proteins that effectively inhibit CDK activity (which reduces yield), the patent uses dominant negative mutants that fail to inhibit CDK activity despite binding the complexes. This inversion of function allows maintaining CDK inhibition effectiveness while improving crop productivity.

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

3Adaptability or versatility

If multiple CKI genes are silenced simultaneously to achieve desired phenotype, then multiple characteristics can be modified, but the complexity and cost increase

Engineering Contradiction:
Improvemultiple characteristic modificationVSAvoidgene silencing system complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent merges the functions of multiple CKI genes into a single dominant negative KRPI protein expression system. By expressing one mutant protein that interferes with multiple CDK-cyclin complexes, the system achieves the effect of silencing multiple genes simultaneously, thereby reducing technical complexity and cost while maintaining versatility.

Inventive Principle:
Principle #5Merging (Combining)

Data Source

PatentEP2422615B1Dominant negative mutant krp protein protection of active cyclin-cdk complex inhibition by wild-type krp
Publication Date: 2014.06.18 TARGETED GROWTH INC
  • EP2422615B1 patent drawingFigure 1A
  • EP2422615B1 patent drawingFigure 1B
  • EP2422615B1 patent drawingFigure 2

AI summary

Disclosed are mutant CDK inhibitor (CKI) polypeptides having dominant negative antagonist activity against wild-type CKI proteins, as well as related compositions, including nucleic acids and vectors encoding the mutant CKI polypeptides and transformed host cells and transgenic plants comprising such nucleic acids and vectors. Also disclosed are related methods for using the mutant proteins to modulate cell division in cells, particularly plant cells.