Methionine Yield via Succinate Dehydrogenase Overexpression
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Solution Overview
Problem
Current methods for fermentative production of methionine face challenges in increasing yield using renewable carbon sources, as high activity of the Krebs cycle enzymes, such as succinate dehydrogenase, is often detrimental to amino acid production, and previous approaches have shown decreased expression of sdh genes to be beneficial, contradicting the finding that increased expression of succinate dehydrogenase enzyme enhances methionine/glucose yield.
Innovation Solution
Enhancing the expression of genes coding for the succinate dehydrogenase enzyme in microorganisms like E. coli by inserting supplementary copies of the sdh genes, thereby overexpressing the enzyme, which increases methionine production when cultured in a medium with a carbon and sulfur source.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If high Krebs cycle activity is maintained, then energy production is sufficient, but amino acid production decreases
Solution Approach 1:
The patent applies inversion by overexpressing succinate dehydrogenase (sdh) genes, which is the opposite of the conventional approach that suggests decreasing sdh expression to reduce Krebs cycle activity. This counterintuitive strategy increases methionine yield from 10.5 g/g to 13.8 g/g glucose by redirecting metabolic flux through the sdh pathway, demonstrating that increased expression of this specific enzyme benefits amino acid production contrary to general Krebs cycle suppression principles
2Productivity
If sdh gene expression is decreased, then CO2 production is reduced, but methionine yield is not improved
Solution Approach 1:
The patent changes the expression level parameter of sdh genes from decreased (conventional approach) to increased (this invention). By overexpressing sdh genes, the patent achieves improved carbon source utilization efficiency, converting glucose to methionine with 30% higher yield (13.8 g/g vs 10.5 g/g), thereby optimizing the parameter of gene expression to resolve the contradiction between CO2 loss and product yield
3Productivity
If renewable carbon sources are used, then sustainability is improved, but methionine production yield is limited
Solution Approach 1:
The patent uses gene copying by inserting multiple copies of sdh genes (sdhC, sdhD, and/or sdhAB) into the microorganism genome or plasmids. This genetic copying strategy enables sustained high-level expression of succinate dehydrogenase, which optimizes metabolic flux through the Krebs cycle and enables high methionine yields (up to 13.8 g/g glucose) from renewable carbon sources, thus resolving the contradiction between sustainability and productivity
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 significantly increases the methionine/carbon source yield, achieving a measurable increase of at least 1% g/g, preferably up to 4%, by optimizing the expression of succinate dehydrogenase in microorganisms like E. coli, thereby improving the fermentative production of methionine.
Implementation Method 1
SQR catalyzes the oxidation of succinate to fumarate in the bacterial cytoplasm with the concomitant reduction of ubiquinone in the membrane
Implementation Method 2
SQR catalyzes the oxidation of succinate to fumarate in the bacterial cytoplasm with the concomitant reduction of ubiquinone in the membrane
Implementation Method 3
a fermentative process comprising the steps of culturing a microorganism modified for an improved production of methionine
Data Source
AI summary
The present invention relates to a process for improving the production of methionine by culturing a microorganism modified for enhancing the expression of genes involved in succinate dehydrogenase synthesis. The microorganisms were modified in a way that the methionine/carbon source yield is increased. The isolation of methionine from the fermentation medium is also claimed.