SAM Regeneration Pathway for Faster Cellular Methyl Compound Production

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Solution Overview

Problem

Existing methods for recycling S-adenosylmethionine (SAM) do not sufficiently accelerate the methylation reaction, and there is a need for a more efficient method to regenerate SAM and produce methyl compounds.

Innovation Solution

Engineering cells to enhance the activity or expression of serine hydroxymethyltransferase (GlyA) and S-adenosylmethionine-dependent methyltransferase, along with other enzymes, to regenerate SAM from organic raw materials like glycine or serine, thereby accelerating the methylation reaction.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If SAM recycling pathway is constructed by adding methanol to culture medium with methylase and methanol dehydrogenase, then SAM can be recycled, but the methylation reaction acceleration is insufficient

Engineering Contradiction:
Improvemethylation reaction rateVSAvoidrecycling pathway complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The invention extracts and optimizes the key enzymatic components (serine hydroxymethyltransferase and methyltransferase) from the complex recycling pathway, focusing on enhancing their activity through gene expression optimization. This approach isolates the critical rate-limiting steps and addresses them directly, achieving better reaction acceleration without the need for complex multi-enzyme systems.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention changes the parameters of enzyme activity and gene expression levels to optimize the methylation reaction. By enhancing the expression of serine hydroxymethyltransferase and methyltransferase genes, and adjusting cultivation conditions, the system achieves higher SAM regeneration efficiency and faster methylation rates without increasing system complexity.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If SAM is supplied in limited amount inside cells, then cellular resources are conserved, but SAM is easily depleted and methylation reaction is limited

Engineering Contradiction:
Improvemethylation reaction rateVSAvoidSAM availability
Core Design Contradiction:
ProductivityVSQuantity of substance

Solution Approach 1:

The invention enables the cell to self-regenerate SAM through enhanced expression of serine hydroxymethyltransferase and methyltransferase. The system uses endogenous serine as a substrate and automatically replenishes SAM levels through the optimized enzymatic pathway, eliminating the need for external SAM supplementation while maintaining high methylation activity.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The invention prepares the cellular machinery in advance by optimizing gene expression levels of key enzymes before the methylation reaction begins. The enhanced enzyme expression ensures that SAM can be rapidly regenerated when needed, preventing depletion and maintaining high reaction rates throughout the process.

Inventive Principle:
Principle #10Preliminary action

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

The method efficiently regenerates SAM and accelerates the methylation reaction, increasing the production of methyl compounds compared to previous methods.

Implementation Method 1

enhance the activity or expression of serine hydroxymethyltransferase (GlyA)

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 2

S-adenosylmethionine-dependent methyltransferase, wherein the methylation reaction is performed in the presence of glycine or serine

Methodology Applied
Scientific EffectMethyl transfer reaction: Chemical Bonding

Data Source

PatentEP4692361A1Method for producing methyl compound
Publication Date: 2026.02.11 MITSUBISHI CHEM CORP
  • EP4692361A1 patent drawingFigure 1
  • EP4692361A1 patent drawingFigure 2
  • EP4692361A1 patent drawingFigure 3

AI summary

An object of the present invention is to provide a novel method that can produce a methyl compound by regenerating SAM and accelerating the methylation reaction of a compound. The present invention provides a method for producing a methyl compound using glycine, serine, or an organic raw material.