Engineered Yeast Beta-Oxidation for Dicarboxylic Acid Production

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Solution Overview

Problem

Current methods for producing fatty dicarboxylic acids are not environmentally friendly and economically competitive, as they often rely on petroleum-derived compounds and generate toxic byproducts, while also lacking efficiency in producing specific diacids with desired chain lengths.

Innovation Solution

Genetically modified yeast strains, such as Candida spp., are engineered to produce diacids from vegetable oil feedstocks using modified acyl-CoA oxidase and dehydrogenase enzymes, which alter the beta-oxidation pathway to enhance production of specific diacids like sebacic and dodecanedioic acid, reducing the need for petroleum-based materials and minimizing environmental impact.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If petroleum-derived compounds are used to produce fatty dicarboxylic acids, then production efficiency is improved, but environmental harm and toxic byproduct generation increase

Engineering Contradiction:
Improveproduction efficiencyVSAvoidenvironmental harm
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The invention changes the fundamental parameter of feedstock source from petroleum-derived compounds to vegetable oil-based feedstocks. This parameter change enables the use of renewable resources while maintaining production capability through engineered microbial pathways that convert plant-derived fatty acids into dicarboxylic acids, thereby resolving the contradiction between productivity and environmental harm

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention replaces chemical synthesis methods with biological synthesis using genetically modified microorganisms. The engineered yeast or fungal cells perform the chemical transformations through natural metabolic pathways, substituting harsh chemical processes with milder biological systems that produce fewer toxic byproducts while maintaining efficient production

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

2Speed

If conventional chemical synthesis methods are used, then production speed is improved, but toxic byproduct generation increases

Engineering Contradiction:
Improveproduction speedVSAvoidtoxic byproducts
Core Design Contradiction:
SpeedVSObject-generated harmful factors

Solution Approach 1:

The invention substitutes conventional chemical synthesis with biological synthesis using engineered microorganisms. The microbial cells perform catalytic transformations through their metabolic pathways, replacing chemical reagents and harsh reaction conditions with enzymatic processes that are inherently more selective and produce fewer toxic byproducts while maintaining production speed

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

Solution Approach 2:

The invention converts the natural metabolic capabilities of microorganisms, which normally serve growth functions, into productive pathways for dicarboxylic acid synthesis. By engineering existing metabolic pathways rather than introducing entirely new chemistry, the system utilizes beneficial biological processes to achieve production goals while minimizing harmful byproduct generation

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

3Object-affected harmful factors

If genetically modified yeast strains are used to produce diacids from vegetable oil, then environmental sustainability is improved, but production complexity increases

Engineering Contradiction:
Improveenvironmental sustainabilityVSAvoidproduction complexity
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The invention segments the complex task of dicarboxylic acid production into manageable genetic modifications of existing metabolic pathways. Rather than creating entirely new systems, the approach divides the problem into specific enzymatic steps within the microbial metabolism that can be independently optimized and controlled, making the overall complex process more tractable

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention uses universal microbial hosts (yeast or fungal cells) that can perform multiple functions: they consume vegetable oil feedstocks, convert them through engineered pathways, and produce dicarboxylic acids. This multi-functionality reduces overall system complexity by using a single biological platform for feedstock conversion, pathway engineering, and product synthesis

Inventive Principle:
Principle #6Universality (Multi-functionality)

4Manufacturing precision

If engineered enzymes are used to alter beta-oxidation pathway, then specificity of diacid production is improved, but enzyme complexity increases

Engineering Contradiction:
Improvespecificity of diacid productionVSAvoidenzyme complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The invention applies local quality by making specific, targeted modifications to enzymes in the beta-oxidation pathway rather than redesigning entire systems. Specific amino acid residues or active sites are modified to confer substrate specificity for producing desired chain-length diacids, while the rest of the enzyme and pathway remains unchanged, thereby achieving precision without excessive complexity

Inventive Principle:
Principle #3Local quality

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 engineered yeast strains efficiently produce diacids with high purity and yield, achieving environmental sustainability and economic competitiveness by utilizing renewable feedstocks and minimizing byproduct toxicity.

Implementation Method 1

modified acyl-CoA oxidase and dehydrogenase enzymes, which alter the beta-oxidation pathway to enhance production of specific diacids

Methodology Applied
Scientific EffectBeta-oxidation:

Implementation Method 2

Genetically modified yeast strains, such as Candida spp., are engineered to produce diacids from vegetable oil feedstocks using modified acyl-CoA oxidase and dehydrogenase enzymes

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Data Source

PatentEP2729564B1Biological methods for preparing a fatty dicarboxylic acid
Publication Date: 2019.09.18 RADICI CHIM
  • EP2729564B1 patent drawingFigure 2
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AI summary

The technology relates in part to biological methods for producing a fatty dicarboxylic acid and engineered microorganisms capable of such production.