Chimeric PUFA PKS System Omega-3 Ratio Control

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Solution Overview

Problem

Current methods for producing polyunsaturated fatty acids (PUFAs) in plants and microorganisms are inefficient, requiring multiple enzymes and resulting in mixed shorter-chain and less unsaturated PUFAs, which are not commercially viable due to contamination issues and limited supply from marine sources.

Innovation Solution

A chimeric PUFA PKS system is created by replacing specific domains of the FabA-like β3-hydroxyacyl-ACP dehydrogenase-2 (DH2) domain from one PUFA PKS system with a homologous domain from another, such as Schizochytrium and Thraustochytrium, to alter the omega-3 to omega-6 PUFA ratio and enhance production, using optimized codon sequences for improved expression.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If traditional PUFA PKS systems are used in plants and microorganisms, then PUFA production is achieved, but the production efficiency is low and mixed shorter-chain and less unsaturated PUFAs are produced

Engineering Contradiction:

ImprovePUFA production efficiencyVSAvoidPUFA chain length and unsaturation specificity

Core Design Contradiction:

ProductivityVSManufacturing precision

Solution Approach 1:

The patent applies local quality by replacing only the DH2 domain of the PUFA PKS system with a homologous domain from a different source (Schizochytrium or Thraustochytrium). This localized modification specifically alters the omega-3 to omega-6 PUFA ratio and enhances production efficiency without requiring complete system replacement, thereby improving productivity while maintaining manufacturing precision for PUFA chain length and unsaturation

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent utilizes parameter changes by optimizing codon sequences for improved expression in host organisms. This nucleotide sequence optimization changes the genetic parameters to enhance protein expression levels, directly improving PUFA production efficiency while maintaining the specificity of the PKS system for producing desired PUFA profiles

Inventive Principle:

Principle #35Parameter changes

2Quantity of substance

If multiple enzymes are used for PUFA production, then PUFA synthesis is achieved, but the process complexity increases and commercial viability decreases

Engineering Contradiction:

ImprovePUFA yieldVSAvoidNumber of enzymes required

Core Design Contradiction:

Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent merges multiple enzymatic functions into a single chimeric PUFA PKS system. By combining the DH2 domain from one PUFA PKS system with a homologous domain from another, the invention creates an integrated system that performs multiple functions (omega-3 and omega-6 PUFA synthesis) within one enzyme complex, thereby reducing the number of separate enzymes required and simplifying the overall production process while maintaining high PUFA yield

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The chimeric PUFA PKS system exhibits multi-functionality by being capable of producing both omega-3 and omega-6 PUFAs with high efficiency. This universal system replaces the need for multiple separate enzymatic pathways, reducing process complexity while maintaining or enhancing PUFA production quantities and commercial viability

Inventive Principle:

Principle #6Universality (Multi-functionality)

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 chimeric system effectively increases the production of desired PUFAs like DHA and alters the omega-3 to omega-6 ratio, leading to higher yields and improved PUFA profiles in genetically modified organisms, addressing the inefficiencies and limitations of existing methods.

Implementation Method 1

A chimeric PUFA PKS system is created by replacing specific domains of the FabA-like β3-hydroxyacyl-ACP dehydrogenase-2 (DH2) domain from one PUFA PKS system with a homologous domain from another

Methodology Applied

Scientific EffectEnzyme catalysis: Enzyme

Data Source

PatentEP2160470B1Chimeric PUFA polyketide synthase systems and uses thereof

Publication Date: 2014.03.05 DSM IP ASSETS BV

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AI summary

Disclosed are chimeric polyunsaturated fatty acid (PUFA) polyketide synthase (PKS) proteins and chimeric PUFA PKS systems, including chimeric PUFA PKS proteins and systems derived from Schizochytrium and Thraustochytrium. Disclosed are nucleic acids and proteins encoding such chimeric PUFA PKS proteins and systems, genetically modified organisms comprising such chimeric PUFA PKS proteins and systems, and methods of making and using such chimeric PUFA PKS proteins and systems.