Meripilus giganteus Protease Variants for Thermo-Stability

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Existing proteases used in starch to ethanol processes lack sufficient storage stability and thermo-stability, which limits their effectiveness in fermentation processes.

Innovation Solution

Development of protease variants with specific modifications at defined positions, such as positions 39, 50, 57, 60, 74, 81, 84, 109, 110, 111, 115, 117, 124, 128, 142, 145, 146, 154, 182, 183, 187, 207, 209, 210, 212, 228, 267, 271, 272, 274, 278, 280, 294, 317, 318, 320, 321, 322, 328, 343, 348, 362, or 363, that exhibit enhanced thermo-stability and residual activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing proteases are used in starch to ethanol processes, then the process can be carried out, but the proteases lack sufficient storage stability and thermo-stability

Engineering Contradiction:
Improvestorage stability and thermo-stabilityVSAvoideffectiveness in fermentation processes
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent applies parameter changes by introducing specific amino acid substitutions at defined positions in the protease sequence. These substitutions modify the physical and chemical parameters of the enzyme structure, resulting in variants with enhanced thermo-stability and storage stability while preserving catalytic activity in fermentation processes.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent implements local quality by making targeted modifications at specific positions (39, 50, 57, 60, 74, 81, 84, 109, 110, 111, 115, 117, 124, 128, 142, 145, 146, 154, 182, 183, 187, 207, 209, 210, 212, 228, 267, 271, 272, 274, 278, 280, 294, 317, 318, 320, 321, 322, 328, 343, 348, 362, or 363) rather than uniform modifications throughout the sequence. This localized approach enhances stability without compromising overall enzyme function.

Inventive Principle:
Principle #3Local quality

2Reliability

If protease variants with modifications at multiple positions are developed, then thermo-stability and residual activity are enhanced, but the complexity of enzyme development increases

Engineering Contradiction:
Improvethermo-stability and residual activityVSAvoidcomplexity of enzyme development
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the protease development process into discrete, manageable components: identifying specific modification positions, selecting amino acid substitutions at each position, and evaluating individual variant properties. This segmented approach to enzyme engineering reduces overall complexity by breaking down the complex task of improving thermo-stability into systematic, testable steps.

Inventive Principle:
Principle #1Segmentation

Data Source

PatentUS12291730B2Serine protease variants and polynucleotides encoding same
Publication Date: 2025.05.06 NOVOZYMES AS

AI summary

The present invention relates to protease variants, having improved properties compared to the parent protease, in particular variants of a serine protease belonging to family 53 derived from a strain of Meripilus giganteus. The variants according to the invention have in particular increased thermo-stability, e.g., increased residual activity after 30 min at a temperature in the range from 55 to 60° C. and/or increased thermal denaturation temperature, compared to the parent Meripilus giganteus protease. The present invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the variants.