Recombinant Microorganism MetE Attenuation Methionine Yield

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Solution Overview

Problem

Current methods for producing pure L-methionine are costly and inefficient, with chemical production methods leading to racemic mixtures and microbial production requiring further optimization, particularly in enhancing the methionine/carbon source yield.

Innovation Solution

A recombinant microorganism with attenuated cobalamin-independent methionine synthase (MetE) activity is developed, achieved by deleting or mutating the metE gene, combined with genetic modifications to enhance expression of certain genes and attenuate others, optimizing the methionine biosynthesis pathway.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If chemical production methods are used to produce pure L-methionine, then production cost increases, but production efficiency improves

Engineering Contradiction:

Improveproduction efficiencyVSAvoidproduction cost

Core Design Contradiction:

ProductivityVSEase of manufacture

Solution Approach 1:

The invention changes the metabolic parameters of the microorganism by deleting the metE gene and overexpressing metH, thereby altering the enzyme activity ratios and metabolic flux distribution to favor L-methionine production. This genetic parameter modification enables microbial production to achieve both high efficiency and cost-effectiveness

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention replaces the chemical synthesis pathway with a biological fermentation pathway. By substituting chemical production methods with genetically engineered microbial fermentation, the process achieves comparable or superior production efficiency while reducing costs and avoiding the racemic mixture problem

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Ease of manufacture

If microbial production methods are used to produce L-methionine, then production cost decreases, but methionine/carbon source yield worsens

Engineering Contradiction:

Improveproduction costVSAvoidmethionine/carbon source yield

Core Design Contradiction:

Ease of manufactureVSQuantity of substance

Solution Approach 1:

The invention modifies key metabolic parameters by deleting metE (reducing cobalamin-independent methionine synthase activity) and overexpressing metH (increasing cobalamin-dependent methionine synthase activity). This parameter change redirects carbon flux toward L-methionine biosynthesis, improving the methionine/carbon source yield while maintaining cost advantages

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention implements metabolic feedback control by manipulating the balance between MetE and MetH enzymes. The overexpression of metH compensates for the loss of metE, ensuring adequate methionine synthesis while optimizing carbon utilization efficiency through feedback regulation of the biosynthetic pathway

Inventive Principle:

Principle #23Feedback

3Quantity of substance

If metE gene is deleted to attenuate cobalamin-independent methionine synthase activity, then methionine/carbon source yield improves, but metabolic pathway complexity increases

Engineering Contradiction:

Improvemethionine/carbon source yieldVSAvoidmetabolic pathway complexity

Core Design Contradiction:

Quantity of substanceVSDevice complexity

Solution Approach 1:

The invention extracts and removes the metE gene from the microbial genome, eliminating the cobalamin-independent methionine synthase pathway. This extraction simplifies the metabolic network by removing a redundant pathway, thereby improving carbon source utilization efficiency while the overexpression of metH ensures adequate methionine production

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

Instead of enhancing both MetE and MetH pathways, the invention inverts the conventional approach by deleting metE and relying primarily on metH overexpression. This inverted strategy simplifies the metabolic pathway while achieving improved methionine/carbon source yield through focused metabolic engineering

Inventive Principle:

Principle #13The other way round (Inversion)

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 significantly improves the methionine/carbon source yield, increasing the production efficiency and reducing production costs by enhancing the recombinant microorganism's ability to produce pure L-methionine.

Implementation Method 1

a method for producing methionine, by culturing the recombinant microorganism in an appropriate culture medium comprising a source of carbon and a source of sulphur

Methodology Applied

Scientific EffectFermentation: Fermentation

Implementation Method 2

the cobalamin-dependent methionine synthase (MetH, EC 2.1.1.13) and The cobalamin-independent methionine synthase (MetE, EC 2.1.1.14)

Methodology Applied

Scientific EffectEnzymatic catalysis: Enzyme

Data Source

PatentUS9506093B2Recombinant microorganism for the fermentative production of methionine

Publication Date: 2016.11.29 EVONIK OPERATIONS GMBH

AI summary

The present invention is related to a recombinant microorganism optimized for the fermentative production of methionine, wherein the activity of the cobalamin-independent methionine synthase MetE is attenuated in said microorganism. The invention is also related to a method for producing methionine by fermentation.