Long-Chain Dibasic Acid Fermentation Strain Reducing Short-Chain Impurities

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Conventional methods for producing long-chain dibasic acid through chemical synthesis result in mixtures requiring complex extraction and purification steps, leading to high production costs and residual impurities, while microbiological fermentation methods struggle with impurity reduction, affecting product quality.

Innovation Solution

Directed evolution of the POX gene through homologous recombination to create a microorganism strain that significantly reduces the content of long-chain dibasic acid impurities during fermentation, specifically targeting the ω-oxidation pathway and inhibiting β-oxidation, resulting in a high-purity long-chain dibasic acid product.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If chemical synthesis method is used to produce long-chain dibasic acid, then production capacity is achieved, but product purity deteriorates due to mixture of long-chain and short-chain dibasic acid requiring complex extraction and purification steps

Engineering Contradiction:
Improveproduction capacityVSAvoidproduct purity
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The invention extracts and removes the harmful short-chain dibasic acid impurities from the fermentation broth through specific purification steps. The patent employs extraction methods using solvents to separate and remove short-chain impurities, achieving high purity long-chain dibasic acid product while maintaining production capacity through the use of genetically modified strains that minimize impurity formation in the first place

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention changes the biological parameters of the producing strain through genetic modification. By modifying genes related to the β-oxidation pathway and introducing improved ω-oxidation enzymes, the patent alters the metabolic parameters of the microorganism to favor long-chain dibasic acid production while suppressing short-chain impurity formation, thereby achieving both high productivity and high purity

Inventive Principle:
Principle #35Parameter changes

2Manufacturing precision

If conventional microbiological fermentation method is used to produce long-chain dibasic acid, then product purity is improved compared to chemical synthesis, but impurity content increases affecting product quality

Engineering Contradiction:
Improveproduct purityVSAvoidimpurity content
Core Design Contradiction:
Manufacturing precisionVSObject-generated harmful factors

Solution Approach 1:

The invention fundamentally changes the biological parameters of the producing strain through genetic modification. By modifying genes related to the β-oxidation pathway and introducing improved ω-oxidation enzymes, the patent alters the metabolic parameters of the microorganism to favor long-chain dibasic acid production while suppressing short-chain impurity formation, thereby achieving both high productivity and high purity

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention converts the harmful β-oxidation pathway that produces short-chain impurities into a beneficial process by genetically modifying the strain to control and minimize this pathway's activity. The patent transforms the naturally occurring impurity-generating mechanism into a controlled process that supports high-purity production by suppressing unwanted side reactions while maintaining the desired ω-oxidation pathway

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

3Reliability

If random mutagenesis is used to improve dibasic acid producing strain, then strain improvement is achieved, but screening throughput requirement increases becoming a limiting factor

Engineering Contradiction:
Improvestrain improvementVSAvoidscreening throughput requirement
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The invention performs preliminary directed genetic modification before fermentation to improve the producing strain. By using targeted gene modification techniques to introduce specific metabolic pathway improvements, the patent eliminates the need for extensive random screening, as the desired traits are built into the strain design phase, thereby reducing screening complexity while maintaining strain improvement reliability

Inventive Principle:
Principle #10Preliminary action

4Productivity

If genetic engineering is used to perform targeted genetic modification of strain, then yield is improved, but manufacturing complexity increases

Engineering Contradiction:
ImproveyieldVSAvoidmanufacturing complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The invention changes the biological parameters of the producing strain through genetic modification to improve yield. By modifying genes related to the β-oxidation pathway and introducing improved ω-oxidation enzymes, the patent alters the metabolic parameters of the microorganism to favor long-chain dibasic acid production, achieving high yield through controlled biological parameter changes rather than complex manufacturing processes

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

The method achieves a substantial decrease in long-chain dibasic acid impurities, improving product quality and simplifying the production process by reducing the complexity and cost of subsequent extraction and purification steps, thereby enhancing the efficiency and purity of long-chain dibasic acid production.

Implementation Method 1

Directed evolution of the POX gene through homologous recombination to create a microorganism strain

Methodology Applied
Scientific EffectHomologous recombination:

Implementation Method 2

specifically targeting the ω-oxidation pathway and inhibiting β-oxidation

Methodology Applied
Scientific Effectω-oxidation: Oxidation

Implementation Method 3

inhibiting β-oxidation, resulting in a high-purity long-chain dibasic acid product

Methodology Applied
Scientific Effectβ-oxidation:

Implementation Method 4

a method for producing a long-chain dibasic acid with low content of long-chain dibasic acid impurity of shorter carbon-chain by using the strain through fermentation

Methodology Applied
Scientific EffectFermentation: Fermentation

Data Source

PatentUS20240254522A1A long chain dibasic acid with low content of long chain dibasic acid impurity of shorter carbon-chain and preparation method thereof
Publication Date: 2024.08.01 CATHAY BIOTECH INC
  • US20240254522A1 patent drawing
  • US20240254522A1 patent drawing

AI summary

The present invention relates to a long-chain dibasic acid with low content of long-chain dibasic acid impurity of shorter carbon chain, to the preparation of a long-chain dibasic acid producing strain by directed evolution of POX gene and homologous recombination, and to the production of a long-chain dibasic acid with low content of long-chain dibasic acid impurity of shorter carbon chain by using the strain. The present invention also relates to a strain containing a mutated promoter, wherein, when a long-chain dibasic acid is produced by fermentation of this strain, the content of the acid impurity of shorter carbon chain in the fermentation product is significantly reduced.