Modified Microorganism Pathway for High-Yield Aspartic Acid Fermentation

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Solution Overview

Problem

Current industrial production of aspartic acid relies on petroleum-derived fumaric acid as a raw material, and there is a lack of effective fermentation techniques using biomass-derived sugars to produce aspartic acid with sufficient production efficiency for industrial applications.

Innovation Solution

Genetically modify microorganisms by reducing or inactivating succinate dehydrogenase, fumarate reductase, and lactate dehydrogenase activities, and impart modified phosphoenolpyruvate carboxylase resistance to feedback inhibition by aspartic acid, using bacteria-derived mutant-type phosphoenolpyruvate carboxylase with specific amino acid mutations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If petroleum-derived fumaric acid is used as raw material for aspartic acid production, then production cost is reduced and large-scale production is achieved, but dependency on petroleum resources increases and environmental sustainability deteriorates

Engineering Contradiction:

Improveproduction efficiencyVSAvoidpetroleum dependency

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The invention changes the raw material parameter from petroleum-derived fumaric acid to biomass-derived glucose, and modifies the biochemical pathway parameters by introducing mutant aspartate dehydrogenase with altered substrate specificity and regulatory properties, enabling efficient aspartic acid production from renewable resources

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention replaces the chemical synthesis route (petroleum-based) with a biological fermentation system using genetically modified microorganisms, substituting chemical processes with biochemical pathways that are more sustainable and environmentally friendly

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Productivity

If aspartate dehydrogenase is introduced into E. coli for fermentative production of aspartic acid, then production from sugar substrates becomes possible, but production efficiency remains insufficient for industrial application

Engineering Contradiction:

Improveproduction efficiencyVSAvoidindustrial applicability

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The invention introduces specific amino acid mutations at key positions of aspartate dehydrogenase (e.g., position 299, 653, 813, 869, 873, 917) to locally alter enzyme properties, enhancing substrate affinity and resistance to feedback inhibition, thereby improving overall production efficiency

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The invention creates mutant versions of aspartate dehydrogenase with optimized properties by copying the wild-type enzyme structure and introducing specific mutations, then expresses these improved enzyme variants in E. coli to achieve industrial-level production efficiency

Inventive Principle:

Principle #26Copying

3Productivity

If wild-type phosphoenolpyruvate carboxylase is used in the metabolic pathway, then normal metabolic function is maintained, but feedback inhibition by aspartic acid limits production efficiency

Engineering Contradiction:

Improveaspartic acid productionVSAvoidmetabolic regulation

Core Design Contradiction:

ProductivityVSStability of the object's composition

Solution Approach 1:

The invention modifies the phosphoenolpyruvate carboxylase parameter by introducing amino acid mutations that reduce feedback inhibition by aspartic acid, allowing the enzyme to maintain high activity even when aspartic acid accumulates, thereby enabling continuous production without metabolic shutdown

Inventive Principle:

Principle #35Parameter changes

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

Improves production efficiency and yield of aspartic acid and its metabolites, enhancing conversion efficiency of sugar substrates and reducing costs through bioprocess optimization.

Implementation Method 1

modified phosphoenolpyruvate carboxylase activity showing resistance to feedback inhibition by aspartic acid

Methodology Applied

Scientific EffectFeedback inhibition: Feedback

Implementation Method 2

succinate dehydrogenase activity

Methodology Applied

Scientific EffectDehydrogenation: Redox Reactions

Implementation Method 3

fumarate reductase activity

Methodology Applied

Scientific EffectReduction: Reduction

Implementation Method 4

lactate dehydrogenase activity

Methodology Applied

Scientific EffectReduction: Reduction

Data Source

PatentUS12600991B2Genetically modified microorganism for production of aspartic acid and downstream metabolites from aspartic acid as target substance, and method for producing target substance using same

Publication Date: 2026.04.14 GREEN EARTH INST CO LTD

AI summary

The present disclosure relates to a genetically modified microorganism satisfying some of predetermined conditions. The predetermined conditions include: (I) succinate dehydrogenase activity or fumarate reductase activity being reduced or inactivated relative to a wild-type microorganism; (II) lactate dehydrogenase activity being reduced or inactivated relative to the wild-type microorganism; (III) the genetically modified microorganism having modified phosphoenolpyruvate carboxylase activity showing resistance to feedback inhibition by aspartic acid in wild-type phosphoenolpyruvate carboxylase activity, or exogenous phosphoenolpyruvate carboxylase activity having higher resistance to feedback inhibition by aspartic acid than that of the wild-type phosphoenolpyruvate carboxylase activity shown by the wild-type microorganism; and (IV) pyruvate:quinone oxidoreductase being reduced or inactivated relative to the wild-type microorganism.