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

VSEngineering 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

Engineering Contradiction:
Improvelactic acid production efficiencyVSAvoidoptical purity
Core Design Contradiction:
ProductivityVSManufacturing precision

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

Inventive Principle:
Principle #2Taking out (Extraction)

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

Inventive Principle:
Principle #35Parameter changes

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

Engineering Contradiction:
Improvelactic acid production rateVSAvoidoptical purity
Core Design Contradiction:
ProductivityVSManufacturing precision

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

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

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

Inventive Principle:
Principle #23Feedback

3Manufacturing precision

If existing gene disruption techniques are applied to inhibit by-product formation, then optical purity improves, but production efficiency decreases

Engineering Contradiction:
Improveoptical purityVSAvoidlactic acid production rate
Core Design Contradiction:
Manufacturing precisionVSProductivity

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

Inventive Principle:
Principle #6Universality (Multi-functionality)

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

Methodology Applied
Scientific EffectRedox reaction: Redox Reactions

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

Methodology Applied
Scientific EffectOxidation-reduction reaction: Redox Reactions

Data Source

PatentUS8614076B2Bacterium capable of producing lactic acid, and method for producing lactic acid
Publication Date: 2013.12.24 MITSUI CHEMICALS INC

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.