Lactonase Enzyme Variants for Thermostability and pH Stability

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Solution Overview

Problem

Native lactonases have limited pH ranges and thermostability, making them ineffective in various applications, particularly in animal feeds where they can be inactivated by temperature and pH in the gastrointestinal tract.

Innovation Solution

Development of variant lactonases with specific amino acid substitutions, such as D66E/E80G/V83I/L136V, that enhance thermostability and pH stability, allowing them to maintain activity under challenging conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If native lactonases are used, then they can degrade AHL molecules, but they have limited pH ranges and thermostability making them ineffective in animal feeds

Engineering Contradiction:
Improveenzyme activityVSAvoidthermostability
Core Design Contradiction:
ReliabilityVSTemperature

Solution Approach 1:

The patent applies parameter changes by modifying amino acid residues at specific positions (66, 80, 83, 136) in the lactonase enzyme sequence. These sequence variations alter the enzyme's physical-chemical parameters to enhance thermostability and broaden pH range, enabling the enzyme to maintain activity under the thermal and pH conditions of animal feed processing and gastrointestinal tract.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If native lactonases are used, then they can degrade AHL molecules, but they are inactivated by temperature and pH in the gastrointestinal tract

Engineering Contradiction:
Improveenzyme activityVSAvoidpH inactivation
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses parameter changes to modify the enzyme's pH stability profile through specific amino acid substitutions. These sequence variations adjust the enzyme's isoelectric point and charge distribution, enabling it to resist inactivation across the pH range encountered in animal gastrointestinal tracts.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If native lactonases are used, then they can degrade AHL molecules, but they are inactivated by temperature in the gastrointestinal tract

Engineering Contradiction:
Improveenzyme activityVSAvoidtemperature inactivation
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes through amino acid substitutions that enhance the enzyme's thermal resistance. The modified sequence increases the energy required for denaturation and stabilizes the folded structure at elevated temperatures, allowing the enzyme to remain active during feed processing and gastrointestinal passage.

Inventive Principle:
Principle #35Parameter changes

4Stability of the object's composition

If amino acid substitutions are made to enhance thermostability, then the enzyme maintains activity under challenging conditions, but the enzyme structure is modified

Engineering Contradiction:
ImprovethermostabilityVSAvoidenzyme structure
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The patent applies local quality by introducing amino acid substitutions at specific local positions (66, 80, 83, 136) within the enzyme sequence rather than throughout the entire structure. These localized modifications target specific structural regions to enhance thermostability while preserving the overall fold and catalytic function of the enzyme.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent uses parameter changes to systematically modify the enzyme's stability parameters through controlled amino acid substitutions. By changing the sequence at specific positions, the enzyme's thermostability parameter is enhanced while maintaining functional integrity.

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 variant lactonases exhibit improved biochemical properties, including increased thermostability and pH stability, making them suitable for use in animal and fish feed products and as antimicrobial agents.

Implementation Method 1

Lactonases are hydrolases that cleave the lactone ring of the AHL rendering them biologically inactive

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 2

Lactonases are hydrolases that cleave the lactone ring of the AHL

Methodology Applied
Scientific EffectHydrolysis: Hydrolysis

Data Source

PatentEP3484293B1Lactonase enzymes and methods of using same
Publication Date: 2021.12.22 FORNIA BIOSOLUTIONS INC
  • EP3484293B1 patent drawingFigure 1
  • EP3484293B1 patent drawingFigure 2
  • EP3484293B1 patent drawingFigure 3

AI summary

Novel lactonases are provided.