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
Engineering 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
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.
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.
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
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.
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
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.
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.
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
Data Source
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.