Lactic Acid Production via Isomer Conversion in Engineered E. coli
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Solution Overview
Problem
Current methods for producing lactic acid with high optical purity face challenges in achieving both high production efficiency and optical purity, particularly when D-lactic acid is present in the medium, as existing techniques struggle to rapidly decompose optical isomers and maintain high lactic acid production rates.
Innovation Solution
The development of a lactic acid-producing Escherichia coli strain with enhanced NAD-dependent lactate dehydrogenase and NAD-independent lactate oxidoreductase activities, which allows for the decomposition of one isomer to produce the other, thereby achieving high optical purity and efficient production of either D-lactic acid or L-lactic acid.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional lactic acid production methods are used, then lactic acid is produced with high efficiency, but by-products are generated and optical purity deteriorates
Solution Approach 1:
The patent extracts and eliminates the harmful factor (D-lactic acid) from the production system by introducing a specific gene disruption (Δdld) that prevents the formation of the unwanted optical isomer, thereby obtaining high optical purity L-lactic acid while maintaining production efficiency
Solution Approach 2:
The patent changes the metabolic parameters of the host organism by disrupting the dld gene, which alters the enzymatic activity profile to favor L-lactic acid production while preventing D-lactic acid formation, thus achieving both high productivity and high optical purity
2Productivity
If D-lactic acid is present in the medium, then production efficiency is maintained, but optical purity decreases due to incorporation of optical isomers
Solution Approach 1:
The patent converts the potentially harmful presence of D-lactic acid in the medium into a beneficial situation by using the Δdld strain, which actively decomposes D-lactic acid through the introduced L-lactate dehydrogenase enzyme, thereby improving optical purity while maintaining production efficiency
Solution Approach 2:
The patent implements a feedback mechanism where the Δdld strain continuously monitors and decomposes D-lactic acid as it is formed or present in the medium, maintaining high optical purity throughout the production process while preserving high productivity
3Manufacturing precision
If existing gene disruption techniques are applied to inhibit by-product formation, then optical purity improves, but production efficiency decreases
Solution Approach 1:
The patent applies a multi-functional approach by disrupting the dld gene, which simultaneously achieves multiple objectives: preventing D-lactic acid formation, maintaining high L-lactic acid production rates, and ensuring high optical purity, thereby eliminating the trade-off between purity 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 enables the rapid production of lactic acid with high optical purity, even when D-lactic acid is present, by simultaneously producing and decomposing optical isomers, thus overcoming the limitations of previous methods.
Implementation Method 1
enhanced so as to decompose one of D-lactic acid or L-lactic acid and to produce the other one of D-lactic acid or L-lactic acid
Implementation Method 2
enhanced so as to decompose one of D-lactic acid or L-lactic acid and to produce the other one of D-lactic acid or L-lactic acid
Data Source
AI summary
The present invention provides: a lactic acid-producing Escherichia coli including an enzymatic activity of at least one NAD-dependent lactate dehydrogenase and an enzymatic activity of at least one NAD-independent lactate oxidoreductase, both of which are enhanced so as to decompose one of D-lactic acid or L-lactic acid and to produce the other one of D-lactic acid or L-lactic acid; and a lactic acid production method using the lactic acid-producing Escherichia coli.