Modified Microorganism Pathway 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 microorganisms are limited by low yield and inefficient dicarboxylic acid excretion, despite conventional wisdom suggesting that decreasing dicarboxylic acid excretion carriers would decrease production.
Innovation Solution
A genetically modified microorganism with decreased dicarboxylic acid excretion carrier function, specifically through deletion or reduction of YjjP, YjjB, YeeA, or YnfM, combined with enhanced 3-oxoadipyl-CoA reductase activity, is developed to increase production yield.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If dicarboxylic acid excretion carrier genes (yjP, yjjB, yeeA, ynfM) are modified to increase expression, then dicarboxylic acid excretion is improved, but production yield of 3-hydroxyadipic acid and α-hydromuconic acid decreases
Solution Approach 1:
The patent applies the inversion principle by deleting or decreasing the function of dicarboxylic acid excretion carrier genes (yjP, yjjB, yeeA, ynfM) instead of increasing their expression as conventional wisdom suggested. This counterintuitive approach prevents the excretion of 3-hydroxyadipic acid and α-hydromuconic acid from the cell, thereby accumulating higher production yields inside the microorganism while maintaining improved dicarboxylic acid excretion capability for other substrates.
2Productivity
If 3-oxoadipyl-CoA reducing enzyme activity is enhanced, then production of 3-hydroxyadipic acid and α-hydromuconic acid is improved, but accumulation of intermediate metabolites may occur
Solution Approach 1:
The patent employs feedback control by combining enhanced 3-oxoadipyl-CoA reducing enzyme activity with deletion of dicarboxylic acid excretion carriers. The increased enzyme activity promotes conversion of 3-oxoadipyl-CoA to 3-hydroxyadipyl-CoA, while the deleted excretion carriers prevent product leakage, creating a feedback loop that maintains metabolic balance and prevents intermediate accumulation by directing flux toward final product formation.
Solution Approach 2:
The patent applies parameter changes by modifying the expression levels of key enzymes in the biosynthetic pathway. Specifically, it enhances the expression of 3-oxoadipyl-CoA reducing enzyme to increase conversion rate, while simultaneously deleting excretion carrier genes to alter the cellular permeability parameter, thereby optimizing both production efficiency and metabolic stability.
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 microorganism achieves higher yields of 3-hydroxyadipic acid and α-hydromuconic acid, contrary to expectations, by optimizing the enzymatic pathway and reducing excretion carriers.
Implementation Method 1
a catalyzing reaction to reduce 3-oxoadipyl-CoA to 3-hydroxyadipyl-CoA
Data Source
AI summary
A genetically modified microorganism that can produce 3-hydroxyadipic acid and/or α-hydromuconic acid with a high yield; and a method of producing 3-hydroxyadipic acid and/or α-hydromuconic acid using the genetically modified microorganism, are disclosed. The genetically modified microorganism has an ability to produce 3-hydroxyadipic acid and/or α-hydromuconic acid, and has an enhanced enzymatic activity to catalyze a reaction to reduce 3-oxoadipyl-CoA to 3-hydroxyadipyl-CoA, wherein, in the genetically modified microorganism, a dicarboxylic acid excretion carrier function is deleted or decreased.