Engineered Bacteria Produce Alpha-Omega Bifunctional Fatty Acids

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Solution Overview

Problem

Current methods for producing hydroxy fatty acids and dicarboxylic fatty acids rely on chemical processes using non-renewable resources, whereas there is a need for sustainable production methods utilizing common, renewable carbon sources like glucose and glycerol.

Innovation Solution

Engineering bacteria to overexpress specific enzymes such as KASIII and acyl-ACP thioesterase, allowing the production of omega-functionalized fatty acids from renewable sources through microbial fermentation, enabling the synthesis of alpha-omega bifunctional fatty acids like hydroxy and dicarboxylic fatty acids without exogenous fatty acid addition.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If chemical processes are used to produce hydroxy fatty acids and dicarboxylic fatty acids, then production efficiency is high, but reliance on non-renewable resources increases

Engineering Contradiction:

Improveproduction efficiencyVSAvoidrenewable resource utilization

Core Design Contradiction:

ProductivityVSAdaptability or versatility

Solution Approach 1:

The patent replaces chemical synthesis processes with biological fermentation processes using engineered microorganisms. The mechanical/chemical system of traditional chemical processes is substituted with a biological system that uses renewable carbon sources like glucose and glycerol to produce hydroxy fatty acids and dicarboxylic fatty acids through metabolic pathways.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent modifies metabolic parameters by engineering specific enzyme expressions (KASIII, FabG, FabA, FabI, and thioesterase) to change the metabolic flow in microorganisms. This allows the biological system to efficiently convert renewable carbon sources into target products, achieving both high productivity and renewable resource utilization.

Inventive Principle:

Principle #35Parameter changes

2Adaptability or versatility

If microbial fermentation is used to produce fatty acids from renewable sources, then sustainability improves, but production efficiency decreases

Engineering Contradiction:

ImprovesustainabilityVSAvoidproduction efficiency

Core Design Contradiction:

Adaptability or versatilityVSProductivity

Solution Approach 1:

The patent divides the fatty acid synthesis pathway into discrete enzymatic steps, each catalyzed by a specific engineered enzyme. By segmenting the metabolic pathway and optimizing each step individually (KASIII for chain initiation, FabG/FabA/FabI for elongation, and thioesterase for product release), the overall production efficiency of the sustainable fermentation process is enhanced.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The engineered microorganism serves multiple functions: it consumes renewable carbon sources (glucose, glycerol), performs biosynthesis of fatty acid chains, and simultaneously produces both hydroxy fatty acids and dicarboxylic fatty acids through coordinated expression of multiple enzyme systems, thereby achieving high productivity within a sustainable framework.

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Stability of the object's composition

If traditional fatty acid synthesis pathways are used, then natural metabolic balance is maintained, but ability to produce alpha-omega bifunctional fatty acids is limited

Engineering Contradiction:

Improvemetabolic balanceVSAvoidproduct customization capability

Core Design Contradiction:

Stability of the object's compositionVSAdaptability or versatility

Solution Approach 1:

The patent introduces an intermediary enzyme system that bridges natural fatty acid synthesis and the production of non-natural alpha-omega bifunctional fatty acids. The engineered KASIII enzyme acts as an intermediary that incorporates omega-functionalized primers (such as 3-hydroxypropionate) into the natural FAS cycle, allowing the production of customized bifunctional fatty acids while maintaining overall metabolic stability.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent dynamically adjusts enzyme expression levels to balance natural metabolic pathways with engineered biosynthetic routes. By controlling the expression of KASIII, FabG, FabA, FabI, and thioesterase genes under appropriate promoters, the system maintains metabolic homeostasis while enabling flexible production of different alpha-omega bifunctional fatty acid products.

Inventive Principle:

Principle #15Dynamics

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 enables the efficient production of alpha-omega bifunctional fatty acids from renewable sources, providing a sustainable, non-destructive, and environmentally friendly method for producing high-value chemicals with customizable chain lengths.

Implementation Method 1

production of omega functionalized fatty acids by engineering bacteria

Methodology Applied

Scientific EffectFermentation: Fermentation

Implementation Method 2

these reactions are catalyzed by a dissociable, type II fatty acid synthase that is composed of the four enzymes 3-ketoacyl-ACP synthase (KAS), 3-ketoacyl-ACP reductase (encoded by fabG), 3-hydroxyacyl-ACP dehydratase (encoded by fabA), and enoyl-ACP reductase (encoded by fabI)

Methodology Applied

Scientific EffectEnzymatic catalysis: Enzyme

Data Source

PatentUS10774349B2Alpha omega bifunctional fatty acids

Publication Date: 2020.09.15 WILLIAM MARCH RICE UNIVERSITY

AI summary

The present disclosure describes an engineered microorganism for producing alpha omega bifunctional C6-16 fatty acids from renewable carbon sources.