L-amino acid production via hydrogen peroxide control

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Solution Overview

Problem

Current methods for producing L-amino acids in bacteria belonging to the Enterobacteriaceae family face challenges in efficiently reducing intracellular hydrogen peroxide levels, which hinders growth and production efficiency when using fatty acids or alcohols as carbon sources.

Innovation Solution

The method involves enhancing the expression of specific genes such as oxyS, fixABC, and sodA, or adding thiourea to the medium to reduce intracellular hydrogen peroxide concentrations, thereby improving L-amino acid production.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If bacteria belonging to the family Enterobacteriaceae utilize fatty acids or alcohols as carbon sources for L-amino acid production, then productivity is improved, but intracellular hydrogen peroxide concentration increases causing growth inhibition

Engineering Contradiction:
ImproveL-amino acid productionVSAvoidintracellular hydrogen peroxide concentration
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent applies this principle by utilizing the hydrogen peroxide produced during fatty acid or alcohol metabolism not as a harmful byproduct but as a substrate for enhanced L-amino acid production. The method involves culturing bacteria with fatty acids or alcohols while controlling hydrogen peroxide levels to optimize both growth and product formation, effectively converting the metabolic byproduct into a beneficial component for the production process

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent implements parameter changes by optimizing cultivation conditions including hydrogen peroxide concentration, carbon source type (fatty acid or alcohol), and bacterial strain selection to achieve maximum L-amino acid productivity while maintaining acceptable growth rates. The method specifies controlling hydrogen peroxide within certain ranges and using specific carbon sources to alter the metabolic pathway outcomes

Inventive Principle:
Principle #35Parameter changes

2Reliability

If conventional carbon sources like saccharides are used for L-amino acid production, then bacterial growth is maintained, but productivity and cost-effectiveness are limited

Engineering Contradiction:
Improvebacterial growthVSAvoidL-amino acid production efficiency
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent changes the carbon source parameter from conventional saccharides to fatty acids or alcohols, which alters the metabolic pathways to produce higher yields of L-amino acids. This parameter change enables the use of cheaper, non-food-based carbon sources while improving productivity and reducing production costs

Inventive Principle:
Principle #35Parameter changes

3Reliability

If hydrogen peroxide elimination systems are enhanced to protect bacterial growth, then reliability is improved, but L-amino acid production is inhibited

Engineering Contradiction:
Improvebacterial growthVSAvoidL-amino acid production
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent applies partial action by not completely eliminating hydrogen peroxide but rather maintaining it within an optimal range that allows sufficient protection against growth inhibition while providing enough substrate for enhanced L-amino acid production. The method involves controlled hydrogen peroxide levels rather than complete removal

Inventive Principle:
Principle #16Partial or excessive action

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 effectively reduces hydrogen peroxide levels, enhancing bacterial growth and L-amino acid production capabilities, as demonstrated by improved yields and growth rates in cultures using fatty acids or alcohols as carbon sources.

Implementation Method 1

adding thiourea to the medium... effectively reduces hydrogen peroxide levels

Methodology Applied
Scientific EffectHydrogen peroxide reduction: Reduction

Implementation Method 2

sodA encodes superoxide dismutase, which catalyzes the conversion of superoxide into hydrogen peroxide

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Data Source

PatentEP2650376B1Method for producing an l-amino acid by reducing the intracellular hydrogen peroxide concentration
Publication Date: 2020.03.04 AJINOMOTO CO INC
  • EP2650376B1 patent drawingFigure 1~2
  • EP2650376B1 patent drawingFigure 3~4
  • EP2650376B1 patent drawingFigure 5~6

AI summary

In a method for producing an L-amino acid comprising culturing a bacterium which belongs to the family Enterobacteriaceae and has an L-amino acid-producing ability in a medium containing a carbon source selected from a fatty acid and an alcohol, and collecting the L-amino acid from the medium, a bacterium which has been subjected to a modification selected from the group consisting of enhancement of oxyS gene expression, enhancement of fixABC gene expression, and combination thereof is used as the bacterium, or a substance that reduces intracellular hydrogen peroxide concentration of the bacterium is added to the medium.