Meso-Diaminopimelate Dehydrogenase Tuning for Higher L-Threonine Yield
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Solution Overview
Problem
Existing methods for producing L-threonine in Corynebacterium glutamicum strains face challenges in increasing production while minimizing L-lysine production without delaying growth rate.
Innovation Solution
A modified polypeptide of meso-diaminopimelate dehydrogenase with weakened activity is introduced, specifically altering the 169th amino acid in the enzyme's sequence, such as substituting it with leucine, phenylalanine, or glutamate, to enhance L-threonine production.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If the ddh gene is deleted to increase L-threonine production, then L-threonine yield is improved, but strain growth is inhibited
Solution Approach 1:
The patent applies parameter changes by modifying the activity level of meso-diaminopimelate dehydrogenase through amino acid substitution at position 169. Instead of complete gene deletion, the enzyme's catalytic activity is reduced to a specific range (10-80% of wild-type activity), which optimizes the balance between L-threonine production and strain growth by adjusting the metabolic flux through the lysine biosynthesis pathway.
Solution Approach 2:
The patent implements partial action by retaining partial activity of the meso-diaminopimelate dehydrogenase enzyme rather than completely eliminating it. The modified enzyme maintains 10-80% of wild-type activity, which is sufficient to support strain growth while partially redirecting metabolic flux toward L-threonine production, avoiding the harmful effects of complete gene deletion.
2Productivity
If the lysE gene is deleted to increase L-threonine production, then L-threonine yield is improved, but growth rate is delayed
Solution Approach 1:
The patent changes the parameter of enzyme activity by introducing amino acid substitutions at position 169 of meso-diaminopimelate dehydrogenase. This modification adjusts the enzyme's catalytic efficiency to an optimal range that allows adequate L-threonine production while maintaining sufficient flux for normal growth rate, thereby resolving the contradiction between productivity and speed.
3Productivity
If meso-diaminopimelate dehydrogenase activity is weakened to increase L-threonine production, then L-threonine yield is improved, but L-lysine production increases
Solution Approach 1:
The patent precisely controls the parameter of enzyme activity by selecting specific amino acid substitutions that reduce meso-diaminopimelate dehydrogenase activity to 10-80% of wild-type levels. This controlled reduction creates an optimal metabolic balance where enough flux is redirected to L-threonine production while preventing excessive L-lysine accumulation, achieving a balanced outcome.
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 modified enzyme maintains strain growth and significantly increases L-threonine yield, offering high industrial production benefits.
Implementation Method 1
meso-diaminopimelate dehydrogenase is an important enzyme which converts piperodeine 2,6-dicarboxylate, that is produced during lysine production in a microorganism, to meso-2,6-diaminopimelate, and fixes a nitrogen source in the lysine production pathway
Data Source
AI summary
The present disclosure relates to a modified polypeptide, in which the activity of meso-diaminopimelate is weakened, and a method for producing L-threonine using the same.