Putrescine Production via Metabolic Pathway Engineering

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Solution Overview

Problem

Current methods for producing putrescine, a precursor in polyamine synthesis, rely on energy-intensive chemical synthesis involving toxic chemicals and high-pressure hydrogen, which is not environmentally friendly and depletes petroleum resources, necessitating a more sustainable and energy-efficient approach.

Innovation Solution

A putrescine-producing microorganism is developed by modifying the Corynebacterium sp. strain to block the ornithine to arginine biosynthetic pathway, increasing intracellular glutamate levels, and introducing ornithine decarboxylase to enhance putrescine production, utilizing a biosynthetic pathway similar to the arginine biosynthesis pathway.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If chemical synthesis is used to produce putrescine, then putrescine can be produced, but energy consumption is high and toxic chemicals are used

Engineering Contradiction:
Improveputrescine productionVSAvoidenergy consumption
Core Design Contradiction:
ProductivityVSUse of energy by moving object

Solution Approach 1:

The patent replaces the chemical synthesis system with a biological system. Specifically, it uses genetically modified microorganisms (Corynebacterium sp. and E. coli) that express ornithine decarboxylase enzyme to catalyze the conversion of ornithine to putrescine. This biological substitution eliminates the need for high-pressure hydrogenation, catalytic oxidation, and toxic cyanide intermediates required in chemical synthesis, while significantly reducing energy consumption and environmental impact.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent introduces ornithine decarboxylase enzyme as a biological intermediary to facilitate putrescine production. The enzyme acts as a catalyst in the biochemical pathway, converting ornithine (derived from arginine or directly from glutamate) to putrescine. This intermediary enzyme system provides a sustainable alternative to chemical catalysts and high-energy processes, enabling efficient putrescine production under mild conditions.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If chemical synthesis is used to produce putrescine, then putrescine can be produced, but harmful factors are generated

Engineering Contradiction:
Improveputrescine productionVSAvoidtoxic chemicals and environmental impact
Core Design Contradiction:
ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent converts the metabolic pathway of microorganisms, which naturally produces ornithine as an intermediate in arginine synthesis, into a beneficial pathway for putrescine production. By introducing ornithine decarboxylase, the microorganisms convert the normally wasted ornithine into valuable putrescine. This approach transforms the biological system's natural metabolism into an environmentally friendly production system that eliminates toxic chemical waste while producing the desired product.

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

3Productivity

If ornithine decarboxylase expression is increased, then putrescine production increases, but metabolic balance may be disrupted

Engineering Contradiction:
Improveputrescine production concentrationVSAvoidmetabolic balance
Core Design Contradiction:
ProductivityVSStability of the object's composition

Solution Approach 1:

The patent optimizes multiple parameters to maintain metabolic balance while increasing putrescine production. This includes controlling the expression level of ornithine decarboxylase, adjusting the availability of ornithine substrate, and optimizing cultivation conditions such as pH, temperature, and aeration. The patent also balances the arginine biosynthesis pathway to ensure sufficient ornithine supply without disrupting overall cellular metabolism, achieving high putrescine titers while maintaining cell viability and metabolic stability.

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

This method enables the production of putrescine at higher concentrations with reduced energy consumption and environmental impact, utilizing biomass and avoiding toxic chemicals, making it a more sustainable alternative for industrial applications.

Implementation Method 1

Putrescine can be synthesized by two pathways such as ornithine decarboxylation or arginine decarboxylation

Methodology Applied
Scientific EffectDecarboxylation:

Implementation Method 2

Production of putrescine in E.coli can be achieved by increasing expression level of ornithine decarboxylase and glutamate acetyltransferase

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Data Source

PatentEP2650357B1Microorganisms for producing putrescine and method for producing putrescine using same
Publication Date: 2019.02.20 CJ CHEILJEDANG CORP
  • EP2650357B1 patent drawingFigure 1
  • EP2650357B1 patent drawingFigure 2
  • EP2650357B1 patent drawingFigure 3

AI summary

The present invention relates to a putrescine-producing microorganism and a method for producing putrescine using the same. To be more specific, the present invention is directed to a microorganism given the ability to produce putrescine which is generated by blocking a biosynthetic pathway from ornithine to arginine, increasing the intracellular level of glutamate, enhancing the biosynthetic pathway of ornithine from glutamate, and introducing extracellular ornithine decarboxylase; and a method for producing putrescine by using the microorganism.