Engineered Microorganisms for Higher 3-Hydroxyadipic Acid Yield
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Solution Overview
Problem
Existing methods for producing 3-hydroxyadipic acid and α-hydromuconic acid using genetically modified microorganisms do not achieve optimal yields, as the metabolic pathways are not fully optimized.
Innovation Solution
Enhance the reactions to generate malic acid from oxaloacetic acid and acetyl-CoA from pyruvic acid in the metabolic pathway of the microorganism through genetic modifications, including increasing the expression and activity of specific enzymes such as malate dehydrogenase, pyruvate dehydrogenase complex, and pyruvate formate-lyase, while avoiding glucose metabolism via the phosphoketolase pathway.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If the metabolic pathway is modified to produce 3-hydroxyadipic acid and/or α-hydromuconic acid, then the production capability is improved, but the yield is not optimal
Solution Approach 1:
The patent applies parameter changes by modifying the expression levels of specific genes (pfl, mdh, pyd) to optimize the metabolic flux. By increasing the expression of pyruvate formate-lyase (pfl), malate dehydrogenase (mdh), and pyruvate dehydrogenase (pyd), the pathway efficiently converts glucose to 3-hydroxyadipic acid and/or α-hydromuconic acid, resolving the contradiction between production capability and yield.
Solution Approach 2:
The patent segments the metabolic pathway into distinct enzymatic steps and optimizes each segment independently. By separately enhancing the activity of pyruvate formate-lyase, malate dehydrogenase, and pyruvate dehydrogenase, the patent achieves cumulative improvement in the overall yield while maintaining production capability.
2Productivity
If existing genetically modified microorganisms are used, then production capability is achieved, but the yield of 3-hydroxyadipic acid and/orα-hydromuconic acid is not optimal
Solution Approach 1:
The patent employs a multi-functional genetic modification strategy where a single microorganism is engineered to simultaneously overexpress multiple enzymes (Pfl, MdH, Pyd) that work together in the metabolic pathway. This universal approach enhances both the production capability and yield by coordinating the function of multiple enzymes within the same biological system.
3Quantity of substance
If the reaction to generate malic acid from oxaloacetic acid is enhanced, then the yield of 3-hydroxyadipic acid and/orα-hydromuconic acid increases, but the metabolic pathway becomes more complex
Solution Approach 1:
The patent utilizes the microorganism's own endogenous genes (pfl, mdh, pyd) to enhance the metabolic pathway. By upregulating the expression of these native genes rather than introducing entirely new pathways, the patent increases yield while minimizing the addition of external genetic elements, thus reducing overall system complexity.
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 genetic modifications lead to significantly higher yields of 3-hydroxyadipic acid and α-hydromuconic acid, enabling their production as raw materials for polyesters and polyamides.
Implementation Method 1
enhancement of the reaction catalyzed by malate dehydrogenase
Implementation Method 2
enhancement of the reaction catalyzed by pyruvate dehydrogenase complex
Implementation Method 3
enhancement of the reaction catalyzed by pyruvate formate-lyase
Data Source
AI summary
Disclosed is a novel genetically modified microorganism showing improved yields of 3-hydroxyadipic acid and/or α-hydromuconic acid. The genetically modified microorganism is a microorganism having an ability to produce 3-hydroxyadipic acid and/or α-hydromuconic acid, in which the reaction to generate malic acid from oxaloacetic acid is enhanced, and the reaction to generate acetyl-CoA from pyruvic acid is enhanced. In addition, the reaction to generate carbon dioxide from formic acid is enhanced.