EF-hand Peptide Mutants for Uranium Chelation

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current uranium biosensors lack the sensitivity and specificity to detect uranyl ions at low concentrations defined by WHO guidelines, and existing systems are not cost-effective for long-term water quality monitoring and bioremediation.

Innovation Solution

Development of new uranium-chelating peptides derived from EF-hand calcium-binding motifs with specific deletions in the calcium-binding loop, enhancing uranyl binding affinity while reducing calcium binding affinity, allowing for sensitive and selective uranyl detection and bioremediation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional EF-hand calcium-binding motifs are used for uranium detection, then the system can detect uranyl ions, but the sensitivity and specificity are insufficient to detect uranyl at low concentrations defined by WHO guidelines

Engineering Contradiction:
Improveuranyl detection sensitivity and specificityVSAvoiddetection reliability at low concentrations
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The EF-hand motif is segmented by deleting specific amino acid residues (positions 2 and 3 in the calcium-binding loop) to create a modified peptide structure that selectively binds uranyl ions while excluding calcium ions, thereby improving detection sensitivity and specificity at low concentrations

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention modifies the local chemical properties of the EF-hand motif by introducing specific deletions and substitutions in the calcium-binding loop region, creating a localized uranyl-binding site with enhanced affinity and selectivity while maintaining the overall protein structure

Inventive Principle:
Principle #3Local quality

2Duration of action of stationary object

If existing uranium biosensors are used for long-term water quality monitoring, then monitoring can be performed, but the systems are not cost-effective

Engineering Contradiction:
Improvelong-term monitoring capabilityVSAvoidcost-effectiveness
Core Design Contradiction:
Duration of action of stationary objectVSEase of manufacture

Solution Approach 1:

The modified EF-hand peptides can be expressed in recombinant cells or organisms for in situ biodetection and bioremediation, eliminating the need for complex external monitoring systems and reducing long-term operational costs while maintaining continuous monitoring capability

Inventive Principle:
Principle #25Self-service

3Quantity of substance

If conventional peptides are used for uranyl binding, then some binding occurs, but the binding affinity and selectivity are insufficient for effective bioremediation

Engineering Contradiction:
Improveuranyl binding affinityVSAvoidselectivity in complex environments
Core Design Contradiction:
Quantity of substanceVSAdaptability or versatility

Solution Approach 1:

The invention changes the chemical parameters of the peptide by deleting residues at positions 2 and 3 and substituting position 1 with a residue that has optimal properties for uranyl coordination, thereby enhancing both binding affinity and selectivity for uranyl ions in complex environmental matrices

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 peptides exhibit significantly higher uranyl binding affinity and specificity, enabling detection of low uranium concentrations in complex media and facilitating effective bioremediation, with the ability to be expressed in recombinant cells or organisms for in situ applications.

Implementation Method 1

new uranium-chelating peptides derived from EF-hand calcium-binding motif useful for uranium biodetection and biodecontamination

Methodology Applied
Scientific EffectChelation:

Implementation Method 2

the ability to be expressed in recombinant cells or organisms for in situ applications

Methodology Applied
Scientific EffectRecombinant expression:

Data Source

PatentEP2981555B1New uranium-chelating peptides derived from EF-hand calcium-binding motif useful for uranium biodetection and biodecontamination
Publication Date: 2020.04.15 COMMISSARIAT A LENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
  • EP2981555B1 patent drawingFigure 1A~1C
  • EP2981555B1 patent drawingFigure 2A~2D
  • EP2981555B1 patent drawingFigure 3A~3B

AI summary

Uranium-chelating polypeptides comprising at least one helix-loop- helix calcium-binding (EF-hand) motif which comprises a deletion of at least two amino acid in the 12-amino-acid calcium-binding loop sequence, and their use for uranium biodetection and biodecontamination.