Mutant Ldc2 Polypeptides for High-Yield Cadaverine Biosynthesis

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Solution Overview

Problem

Current methods for cadaverine production, such as fermentative production and in vitro enzyme catalysis, result in low yields, necessitating a more effective process to enhance cadaverine production.

Innovation Solution

The use of a transformant comprising an expression plasmid vector in Escherichia coli (E. coli) or Hafnia alvei cells with specific mutants of the Ldc2 polypeptide, such as S111C, N262T, K265N, S111C/N262T, S111C/K265N, N262T/K265N, and S111C/N262T/K265N, to increase cadaverine yields through improved lysine decarboxylation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If traditional lysine decarboxylases (CadA or LdcC) are used in fermentative production, then the lysine biosynthesis pathway can be extended to cadaverine biosynthesis, but the cadaverine production yield remains low

Engineering Contradiction:
Improvecadaverine production yieldVSAvoidproduction efficiency
Core Design Contradiction:
Quantity of substanceVSProductivity

Solution Approach 1:

The patent applies parameter changes by introducing specific mutations at positions 111, 262, and 265 of the Ldc2 enzyme sequence. These amino acid substitutions (S111C, N262T, K265N) modify the enzyme's catalytic parameters to enhance lysine decarboxylation activity, directly increasing cadaverine production yield from low levels to unexpectedly high yields

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses copying by creating recombinant expression constructs of the mutated ldc2 gene and introducing them into host bacteria. The mutant Ldc2 polypeptide sequences are copied and expressed in E. coli or Hafnia alvei cells, replacing or supplementing the traditional CadA or LdcC enzymes to achieve improved cadaverine production

Inventive Principle:
Principle #26Copying

2Quantity of substance

If in vitro enzyme catalysis is used with traditional lysine decarboxylases, then lysine can be converted to cadaverine, but the conversion yield is limited

Engineering Contradiction:
Improvecadaverine conversion yieldVSAvoidprocess simplicity
Core Design Contradiction:
Quantity of substanceVSEase of manufacture

Solution Approach 1:

The patent modifies the enzymatic conversion parameters by introducing specific amino acid mutations (S111C, N262T, K265N) in the Ldc2 enzyme. These parameter changes enhance the decarboxylation efficiency and substrate affinity, enabling higher cadaverine conversion yields while maintaining the simplicity of the in vitro enzyme catalysis approach

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

This approach leads to unexpectedly high cadaverine production yields, exceeding those achieved with traditional E. coli lysine decarboxylases like CadA, demonstrating the effectiveness of the mutant Ldc2 polypeptides in enhancing cadaverine biosynthesis.

Implementation Method 1

Lysine decarboxylases are the enzymes that catalyze production of cadaverine by removing the carboxyl group from lysine

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Data Source

PatentEP3161125B1Expression of polypeptides involved in lysine decarboxylation, and methods and applications thereof
Publication Date: 2021.02.17 CIBT AMERICA INC
  • EP3161125B1 patent drawingFigure 1
  • EP3161125B1 patent drawingFigure 2
  • EP3161125B1 patent drawingFigure 3

AI summary

The expression plasmid vectors comprise a polynucleotide sequence encoding Ldc2 polypeptide, a fragment, and/or a mutant. A backbone plasmid is capable of autonomous replication in a host cell. The host cell is not a P. aeruginosa cell. Transformants are transformed with expression plasmid vector. The transformants are not P. aeruginosa.Mutant host cells comprise a polynucleotide sequence encoding Ldc2 polypeptide, a fragment and/or a mutant that has been integrated into the host cell chromosome. A polypeptide, a fragment and/or a mutant comprise Ldc2. A non-naturally occurring polynucleotide, and/or a mutant encodes polypeptide comprising Ldc2. Biobased cadaverine is produced using the transformants and the biobased cadaverine is prepared by the method. Polyamides are formed using the biobased cadaverine and compositions.