Microbial n-butyraldehyde production via in-situ sparging

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Solution Overview

Problem

Current methods for producing n-butyraldehyde, such as hydroformylation and microbial production, face challenges including low yield, high energy consumption, and environmental unfriendliness, with existing microbial methods suffering from low yields and high recovery costs.

Innovation Solution

Genetically engineered microorganisms are used to convert saccharides into n-butyraldehyde through a series of enzyme-catalyzed steps, with a sparging process to remove the product during fermentation, achieving higher yields and preventing degradation by reducing or eliminating certain alcohol dehydrogenases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If hydroformylation process is used to produce C4 oxo-chemicals, then production capacity is sufficient, but energy consumption is high and environmental impact is negative

Engineering Contradiction:
Improveproduction capacityVSAvoidenergy consumption
Core Design Contradiction:
ProductivityVSUse of energy by moving object

Solution Approach 1:

The patent changes the fundamental parameters of the production system by replacing high-temperature/high-pressure chemical catalysis with mild-temperature microbial fermentation. The hydroformylation process operates at high temperature and pressure to achieve sufficient production capacity, while the microbial conversion process maintains productivity through optimized fermentation conditions and continuous product removal, thereby reducing energy consumption without sacrificing production output.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent replaces the mechanical/chemical system of hydroformylation (requiring high temperature, pressure, and catalysts) with a biological system using genetically engineered microorganisms. This substitution eliminates the need for extreme operating conditions and toxic catalysts, reducing energy consumption and environmental impact while maintaining production capacity through efficient microbial metabolism and product recovery systems.

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

2Object-generated harmful factors

If conventional microbial production methods are used to produce n-butyraldehyde, then renewable resources are utilized, but yield is low and recovery cost is high

Engineering Contradiction:
Improveenvironmental impactVSAvoidyield
Core Design Contradiction:
Object-generated harmful factorsVSProductivity

Solution Approach 1:

The patent applies preliminary action by genetically engineering the microorganisms before fermentation to overproduce key enzymes (acetyl-CoA synthetase, phosphotransacetylase, acetate kinase, and alcohol dehydrogenase) and delete competing pathways (pyruvate decarboxylase and acetaldehyde dehydrogenase). This pre-optimization of the metabolic pathway ensures high n-butyraldehyde yield during fermentation, eliminating the need for post-fermentation pathway manipulation and reducing recovery costs.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent implements continuous useful action by continuously removing n-butyraldehyde from the fermentation broth during the fermentation process using in-situ product removal (ISPR) technology. This continuous removal prevents product inhibition, maintains high fermentation rates, and increases overall yield while reducing the complexity and cost of downstream recovery operations compared to batch removal methods.

Inventive Principle:
Principle #20Continuity of useful action

3Ease of manufacture

If Clostridium species are used to produce 1-butanol, then microbial conversion is achieved, but separation cost is high and genetic modification is limited

Engineering Contradiction:
Improvemicrobial conversion capabilityVSAvoidseparation complexity
Core Design Contradiction:
Ease of manufactureVSDevice complexity

Solution Approach 1:

The patent applies the extraction principle by continuously removing n-butyraldehyde from the fermentation broth during the fermentation process using in-situ product removal (ISPR) technology. This extraction of the product during production prevents accumulation and simplifies downstream separation, reducing the complexity of post-fermentation processing compared to methods that require complete fermentation before separation.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent inverts the conventional approach by not relying on Clostridium species that naturally produce 1-butanol requiring separation, but instead using easily genetically modified microorganisms like E. coli or S. cerevisiae engineered to produce n-butyraldehyde directly. This inversion of the production strategy simplifies both genetic modification and product recovery, eliminating the separation complexity associated with 1-butanol production methods.

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 results in significantly higher cumulative yields of n-butyraldehyde, maintaining cell viability, and increasing production efficiency while reducing environmental impact by using renewable resources.

Implementation Method 1

the produced n-butyraldehyde is removed by a sparging process while the microorganism is cultured

Methodology Applied
Scientific EffectGas stripping: Sparging

Implementation Method 2

the condensation product is subsequently reduced over multiple steps to n-butyraldehyde

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Data Source

PatentEP2773761B1Microbial production of n-butyraldehyde
Publication Date: 2019.03.06 EASEL BIOTECHNOLOGIES LLC
  • EP2773761B1 patent drawingFigure 1
  • EP2773761B1 patent drawingFigure 2A
  • EP2773761B1 patent drawingFigure 2B

AI summary

Microorganisms and methods of producing n-butyraldehyde with enhanced yields are presented in which a microorganism is engineered to enhance the conversion of a carbon source into n-butyraldehyde. The n-butyraldehyde is recovered by way of a gas stripping process that occurs during the conversion process, providing significantly greater product yield than post-fermentation recovery of n-butyraldehyde alone.