Stabilized Transglutaminase Pro-Sequence Peptide Binding

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Solution Overview

Problem

Despite existing stabilization techniques, transglutaminases still require additional components to maintain stability, particularly in food applications, where minimal extra additions are desirable.

Innovation Solution

A stabilized transglutaminase is produced by binding a pro-sequence peptide to mature transglutaminase, enhancing stability against pH, temperature, oxidation, and storage conditions, using a microorganism like Streptomyces mobaraensis and specific amino acid sequences.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If additional stabilizers (organic acid, inorganic acid, polyphenol, thiol, sugar alcohol, or protein) are added to transglutaminase, then stability during storage is improved, but the complexity of the system and the number of extra components increase

Engineering Contradiction:
Improvestability during storageVSAvoidnumber of extra components
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The transglutaminase molecule itself provides stabilization through its pro-form structure. The pro-sequence peptide remains bound to the mature transglutaminase, creating a self-stabilizing system that does not require external stabilizers. This self-service approach resolves the contradiction by making the enzyme self-sufficient for stability while minimizing extra components.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The pro-form transglutaminase represents a composite structure where the pro-sequence peptide and mature transglutaminase function together as an integrated stabilizing system. This internal composite structure provides stability without requiring separate stabilizing agents, thus resolving the contradiction between stability improvement and component complexity.

Inventive Principle:
Principle #40Composite materials

2Reliability

If transglutaminase is used in food applications, then protein binding and food manufacturing are improved, but the risk of unexpected circumstances increases without sufficient stabilization

Engineering Contradiction:
Improveperformance in food applicationsVSAvoidunexpected circumstances
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The pro-sequence peptide acts as a protective cushion that remains bound to the mature transglutaminase before food processing applications. This pre-existing protective structure cushions the enzyme against destabilizing conditions during storage and application, ensuring reliable performance while minimizing risks of unexpected circumstances.

Inventive Principle:
Principle #11Beforehand cushioning (Prior cushioning)

Solution Approach 2:

The invention changes the structural parameter of transglutaminase by maintaining the pro-form with bound pro-sequence peptide rather than using the mature form alone. This parameter change (structural configuration) fundamentally alters the stability profile, providing enhanced reliability in food applications without requiring additional stabilizing parameters or components.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If mature transglutaminase is used, then enzymatic activity is achieved, but stability against oxidation, temperature, and pH is poor

Engineering Contradiction:
Improveenzymatic activityVSAvoidstability against oxidation, temperature, and pH
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The invention merges the pro-sequence peptide with the mature transglutaminase in a stable complex structure. This merging creates a unified molecule where the pro-sequence peptide and mature enzyme work together, combining the enzymatic activity of the mature form with the stabilizing properties of the pro-sequence, thus resolving the contradiction between activity and stability.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The pro-sequence peptide acts as an intermediary element that mediates between the mature transglutaminase and the destabilizing environmental factors (oxidation, temperature, pH). This intermediary structure protects the active site and overall enzyme structure from harmful effects while maintaining enzymatic function, resolving the contradiction between activity and stability.

Inventive Principle:
Principle #24Intermediary (Mediator)

Data Source

PatentEP2251421B1Stabilized transglutaminase and process for production thereof
Publication Date: 2016.11.16 AMANO ENZYME INC
  • EP2251421B1 patent drawingFigure 1
  • EP2251421B1 patent drawingFigure 2
  • EP2251421B1 patent drawingFigure 3

AI summary

Disclosed is a transglutaminase having excellent stability. Also disclosed is a process for producing the transglutaminase. Specifically disclosed is a stabilized transglutaminase, which has such a structure in which a pro-sequence peptide of transglutaminase is bound to a mature transglutaminase. Also specifically disclosed is a process for producing stabilized transglutaminase, which includes the steps of: culturing a microorganism capable of producing transglutaminase under the conditions where transglutaminase can be produced; and separating and collecting matured transglutaminase having a pro-sequence peptide bound thereto from a culture medium.