Dimethyl Disulfide Methionine Production Microbial Pathways

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Solution Overview

Problem

Current methionine production methods, both chemical and fermentative, face challenges due to the use of toxic, dangerous, and noxious materials like methane thiol, and are inefficient in terms of sulfur source utilization, leading to economic and ecological issues.

Innovation Solution

The use of dimethyl disulfide (DMDS) as a sulfur and methyl group source in microbial cultures, bypassing the need for MetH/MetE and MetF activity, and enabling methionine production through a deregulated methionine biosynthetic pathway, with DMDS being added to the culture media at concentrations effective for methionine synthesis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If methane thiol is used as a sulfur source for methionine production, then the sulfur atom is already reduced and a methyl group is supplied, but the compound is toxic, explosive, and noxious

Engineering Contradiction:

Improvemethionine production efficiencyVSAvoidtoxicity and safety hazards

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent converts the harmful properties of methane thiol into beneficial properties by using dimethyl disulfide, which is a stable, non-toxic compound that can be safely handled. The disulfide bond in DMDS allows it to serve as a sulfur source that microorganisms can metabolize to produce methionine, effectively converting a hazardous material problem into a safe and efficient production method

Inventive Principle:

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

Solution Approach 2:

The patent changes the chemical parameters of the sulfur source from methane thiol (CH3SH) to dimethyl disulfide (CH3SSCH3). This parameter change maintains the essential functional properties (providing sulfur and methyl groups) while eliminating the harmful characteristics (toxicity, explosiveness) through molecular structure modification

Inventive Principle:

Principle #35Parameter changes

2Object-affected harmful factors

If sulfate is used as a sulfur source for methionine production, then the process is safer and less toxic, but the sulfur atom must be reduced first which is energy intensive

Engineering Contradiction:

Improvetoxicity reductionVSAvoidenergy consumption for sulfur reduction

Core Design Contradiction:

Object-affected harmful factorsVSUse of energy by moving object

Solution Approach 1:

The patent applies preliminary action by providing a sulfur source (dimethyl disulfide) that is pre-reduced, eliminating the need for microorganisms to perform energy-intensive reduction of sulfate. The disulfide bonds in DMDS are already in a reduced state, allowing microorganisms to directly incorporate the sulfur into methionine without additional energy expenditure for reduction reactions

Inventive Principle:

Principle #10Preliminary action

3Productivity

If the chemical synthesis process is used for methionine production, then DL-methionine can be produced, but toxic intermediates and large excess of unused compounds are generated

Engineering Contradiction:

Improvemethionine production capacityVSAvoidtoxic intermediates and waste

Core Design Contradiction:

ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent replaces the chemical synthesis system with a biological system (fermentative process using microorganisms). Instead of using chemical reagents and catalysts that produce toxic intermediates, living cells are used to biosynthesize methionine through metabolic pathways, naturally eliminating the formation of harmful chemical intermediates and reducing waste

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

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 allows for improved methionine production with reduced toxicity and environmental impact, utilizing a less hazardous compound that is more efficient in sulfur utilization, thereby addressing the limitations of existing methods.

Implementation Method 1

Methodology Applied

Scientific EffectMetabolism: Fermentation

Data Source

PatentEP1907558B1Use of dimethyl disulfide for methionine production in microorganisms

Publication Date: 2010.11.24 EVONIK OPERATIONS GMBH

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AI summary

The present invention features improved processes and organisms for the production of methionine. The invention demonstrates that a ΔmetF organism or a ΔmetE AmetH organism, for example, mutants of C. glutamicum or E. coli, can use a methyl capped sulfide source, e.g., dimethyl disulfide (DMDS), as a source of both sulfur and a methyl group, bypassing the need for MetH/MetΕ and MetF activity and the need to reduce sulfate, for the synthesis of methionine. Also described in this patent are data implicating MetY (also called MetZ) as an enzyme that incorporates a methyl capped sulfide source, e.g., DMDS, into methionine. A ΔmetF ΔmetB strain of C. glutamicum can use a methyl capped sulfide source, e.g., DMDS, as a source of both sulfide and a methyl group. Furthermore, methionine production by engineered prototrophic organisms that overproduce O-acetyl-homoserine was improved by the addition of a methyl capped sulfide source, e.g., DMDS.