Mutated Human Acidic Chitinase Hyperactivation

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Solution Overview

Problem

Human acidic chitinase (Chia) has lower activity compared to mouse Chia, limiting its therapeutic potential for treating diseases such as asthma and lung fibrosis.

Innovation Solution

Introduction of specific mutations (R61M, M162T, I173S, M179L, N190T, V246A, D252N, N270T, I272L, and I300F) into the human Chia enzyme, resulting in hyperactivated Chia with enhanced chitinase activity, thermostability, and pH stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If human wild-type Chia is used, then the enzyme maintains natural pH optimum and stability, but chitinase activity is low (1/50 of mouse Chia)

Engineering Contradiction:

Improvechitinase activityVSAvoidpH stability

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent applies parameter changes by introducing specific amino acid substitutions (R61M, M162T, I173S, M179L, N190T, V246A, D252N, N270T, I272L, I300F) to modify the enzyme's catalytic efficiency and pH stability parameters, transforming human Chia from low activity to hyperactivated form with enhanced therapeutic potential

Inventive Principle:

Principle #35Parameter changes

2Productivity

If human wild-type Chia is used, then the enzyme structure is simple and well-defined, but therapeutic effectiveness is limited due to low activity

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidenzyme structure complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent applies local quality by introducing mutations at specific localized positions (10 specific amino acid positions) within the enzyme structure, rather than globally modifying the entire protein, thereby achieving enhanced activity while maintaining overall structural integrity and simplicity

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

The mutated human Chia exhibits significantly increased chitinase activity across various pH conditions and temperatures, effectively degrading both low-molecular-weight and high-molecular-weight chitin substrates, making it suitable for treating respiratory and digestive disorders.

Implementation Method 1

Chitinase is an enzyme that catalyzes the hydrolysis of chitin, a polymer composed of N-acetyl-D-glucosamine

Methodology Applied

Scientific EffectHydrolysis: Hydrolysis

Data Source

PatentEP4559519A1Mutated human acidic chitinase for medical use

Publication Date: 2025.05.28 BIOINOVA AS

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Figure 2B~2C
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AI summary

The present invention provides a mutated human acidic chitinase having amino acid sequence of the wild type human Chia and bearing the following mutations: R61M, M162T, I173S, M179L, N190T, V246A, D252N, N270T, I272L, and I300F. These mutations hyperactivate the acidic chitinase which is particularly suitable for medical uses.