L-Glutamine-Resistant Corynebacterium Mutants for High-Yield Production

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Solution Overview

Problem

Existing methods for producing L-glutamine face challenges in achieving high productivity due to feedback inhibition by high concentrations of L-glutamine, which suppresses glutamine synthetase activity and limits biosynthesis.

Innovation Solution

Development of a Corynebacterium glutamicum mutant resistant to high concentrations of L-glutamine, such as strains KCCM 11553P and KCCM11554P, which can maintain or increase L-glutamine production even in environments with elevated L-glutamine levels, achieved through mutagenesis using agents like N-methyl-N'-nitro-N-nitrosoguanidine, allowing for higher yields.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If high concentrations of L-glutamine are accumulated in the culture medium, then L-glutamine productivity is improved, but feedback inhibition occurs that suppresses glutamine synthetase activity and limits further biosynthesis

Engineering Contradiction:
ImproveL-glutamine productivityVSAvoidfeedback inhibition
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent applies the principle of converting harm into benefit by transforming the harmful feedback inhibition effect into a beneficial resistance mechanism. Through mutagenesis, the microorganism develops resistance to L-glutamine, allowing it to tolerate and even thrive in high concentrations of the product it produces. This converts the previously harmful feedback inhibition into a beneficial condition where the organism can maintain high productivity without being suppressed by accumulated L-glutamine.

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

Solution Approach 2:

The patent applies parameter changes by modifying the microorganism's physiological parameters through mutagenesis. The mutant strain exhibits altered sensitivity parameters regarding L-glutamine concentration, specifically developing resistance that changes the feedback inhibition dynamics. This allows the organism to operate at higher L-glutamine concentrations where the product inhibition is effectively overcome, thereby improving overall productivity.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If conventional microorganisms are used for L-glutamine production, then production can be maintained at low to moderate levels, but productivity cannot be improved beyond a certain limit due to feedback inhibition

Engineering Contradiction:
ImproveL-glutamine yieldVSAvoidbiosynthesis stability
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent transforms the unreliable biosynthesis limitation into a reliable high-productivity system by developing mutant strains that are resistant to L-glutamine feedback inhibition. The mutagenesis process creates organisms that reliably maintain high productivity without being constrained by the feedback inhibition that limits conventional strains.

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

3Productivity

If L-glutamine concentration in the medium is increased to improve productivity, then yield increases, but the microorganism's growth and activity are inhibited by the high concentration

Engineering Contradiction:
ImproveL-glutamine yieldVSAvoidmicroorganism survival in high concentration medium
Core Design Contradiction:
ProductivityVSEase of operation

Solution Approach 1:

The patent converts the operational difficulty of maintaining microorganism survival in high L-glutamine medium into an advantage. Through mutagenesis, the organisms develop resistance that allows them to not only survive but thrive in high concentrations of L-glutamine, transforming the previously inhibitory condition into a favorable environment for high-yield production.

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

Solution Approach 2:

The patent changes the microorganism's physiological parameters through mutagenesis, specifically altering its sensitivity threshold and tolerance range for L-glutamine concentration. This parameter change enables the organism to operate effectively in high-concentration media that would previously have been inhibitory, thereby facilitating ease of operation at improved productivity levels.

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 L-glutamine-resistant mutants demonstrate improved productivity with yields 10% higher than parent strains, capable of surviving and producing L-glutamine in media with concentrations up to 25 g/L, facilitating efficient industrial-scale production.

Implementation Method 1

Development of a Corynebacterium glutamicum mutant resistant to high concentrations of L-glutamine, such as strains KCCM 11553P and KCCM11554P, which can maintain or increase L-glutamine production even in environments with elevated L-glutamine levels, achieved through mutagenesis using agents like N-methyl-N'-nitro-N-nitrosoguanidine

Methodology Applied
Scientific EffectMutagenesis:

Data Source

PatentEP3205714B1Microorganism for producing l-glutamine and method for producing l-glutamine using same
Publication Date: 2020.08.05 CJ CHEILJEDANG CORP

AI summary

Provided are a Corynebacterium glutamicum mutant that is resistant to high concentrations of L-glutamine, and a method of producing L-glutamine by using the mutant.