Variant Protease Amino Acid Substitutions for Cleaning Stability

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Solution Overview

Problem

There is a need for improved variant proteases for cleaning applications, as existing proteases do not fully meet the requirements for various uses, such as laundry and dishwashing, despite previous developments in modified proteases and cleaning compositions.

Innovation Solution

The development of variant proteases with specific amino acid substitutions, such as N76D+S87R+G118R+S128L+P129Q+S130A, which provide a balanced charge and improved proteolytic activity, are integrated into cleaning compositions to enhance wash performance and stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing proteases are used in cleaning applications, then basic proteolytic activity is provided, but wash performance and stability are insufficient

Engineering Contradiction:
ImprovestabilityVSAvoidwash performance
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent applies parameter changes by systematically modifying amino acid residues at specific positions (76, 87, 118, 128, 129, 130, 188, and 244) in the subtilisin sequence. These positional parameters were identified through structure-function analysis, and changing the amino acid composition at these positions creates variants with optimized charge distribution, resulting in improved stability and wash performance compared to wild-type proteases.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent applies local quality by making targeted amino acid substitutions at specific positions rather than random mutagenesis. Positions 76, 87, 118, 188, and 244 were identified as critical for charge distribution and stability, while positions 128, 129, and 130 were targeted for optimizing substrate binding. This localized modification approach allows precise control over protease properties while maintaining overall structural integrity.

Inventive Principle:
Principle #3Local quality

2Productivity

If amino acid substitutions are made to improve proteolytic activity, then wash performance increases, but protein structure stability may be compromised

Engineering Contradiction:
Improveproteolytic activityVSAvoidprotein structure stability
Core Design Contradiction:
ProductivityVSStability of the object's composition

Solution Approach 1:

The patent systematically changes amino acid parameters at specific positions to optimize the balance between proteolytic activity and structural stability. By selecting amino acids with appropriate charge properties and side chain characteristics at positions 76, 87, 118, 188, and 244, the invention achieves enhanced proteolytic activity while the overall subtilisin fold and catalytic triad remain intact, maintaining structural stability.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If multiple amino acid positions are modified to optimize charge distribution, then overall performance improves, but the complexity of protein engineering increases

Engineering Contradiction:
Improveoverall performanceVSAvoidprotein engineering complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent reduces engineering complexity by focusing modifications on a limited set of critical positions (76, 87, 118, 128, 129, 130, 188, and 244) rather than attempting to optimize the entire protein sequence. Structure-function analysis identified these specific positions as having the greatest impact on charge distribution and performance, allowing targeted mutagenesis strategies that are more manageable than comprehensive protein redesign.

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

These variant proteases demonstrate improved wash performance and stability in cleaning applications, outperforming existing proteases by effectively breaking down proteins and maintaining activity under different conditions.

Implementation Method 1

effectively breaking down proteins and maintaining activity under different conditions

Methodology Applied
Scientific EffectProteolysis: Hydrolysis

Data Source

PatentEP2558573B1Compositions and methods comprising variant proteases
Publication Date: 2017.02.22 DANISCO US INC
  • EP2558573B1 patent drawingFigure 1
  • EP2558573B1 patent drawingFigure 2

AI summary

The present invention provides variant proteases, compositions comprising such variant proteases, and methods of cleaning comprising such variant proteases.