CoA-Dependent Carbon Chain Elongation for C6 Building Blocks

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current methods for producing adipic acid, caprolactam, 6-aminohexanoic acid, 6-hydroxyhexanoic acid, hexamethylenediamine, and 1,6-hexanediol are not sustainable and face challenges in directing carbon flux towards these C6 building blocks due to the optimality principle, which prioritizes biomass growth over production, and lack efficient biocatalytic pathways.

Innovation Solution

Construction of biochemical pathways using CoA-dependent elongation enzymes and specific enzymes like thioesterases, ω-transaminases, and monooxygenases to form six carbon chain aliphatic backbones and terminal functional groups, allowing for the biosynthesis of these C6 building blocks through metabolic engineering and appropriate cultivation strategies.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If biocatalysis is used to produce C6 building blocks from biomass, then sustainability is improved, but productivity is reduced due to the optimality principle prioritizing biomass growth over product production

Engineering Contradiction:

ImprovesustainabilityVSAvoidproduction efficiency

Core Design Contradiction:

Object-affected harmful factorsVSProductivity

Solution Approach 1:

The patent changes key metabolic parameters by introducing heterologous enzymes (β-ketothiolase, dehydrogenases, reductases, hydratases, thioesterases) to alter the metabolic flux distribution. This redirects carbon flow from biomass growth pathways to C6 building block production pathways, overcoming the optimality principle constraint while maintaining biocatalytic sustainability

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses engineered metabolic pathways with intermediate compounds (acetyl-CoA, malonyl-CoA, 3-oxohexanoyl-CoA, hexanoyl-CoA) as mediators to transform biomass feedstocks into C6 building blocks. These intermediates serve as carriers that enable the conversion process while managing the trade-off between growth and production

Inventive Principle:

Principle #24Intermediary (Mediator)

2Productivity

If conventional petrochemical methods are used, then productivity is high, but sustainability deteriorates due to reliance on non-renewable feedstocks

Engineering Contradiction:

Improveproduction efficiencyVSAvoidsustainability

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces petrochemical feedstocks and chemical oxidation processes with biocatalytic systems using renewable biomass and engineered enzymatic pathways. This substitution maintains production capability while eliminating dependence on non-renewable resources and reducing environmental harm

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent fundamentally changes the feedstock parameter from petrochemical sources to biomass-derived substrates, and alters the reaction conditions to use mild biocatalytic processes instead of harsh chemical treatments, achieving both sustainability and productivity

Inventive Principle:

Principle #35Parameter changes

3Productivity

If carbon flux is directed towards C6 building blocks through metabolic engineering, then productivity improves, but the complexity of the biochemical network increases

Engineering Contradiction:

ImproveC6 building block productionVSAvoidbiochemical network complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent segments the complex biosynthesis pathway into discrete enzymatic steps, each catalyzed by a specific engineered enzyme (β-ketothiolase for chain initiation, dehydrogenases for oxidation, reductases for reduction, hydratases for hydration, thioesterases for chain release). This modular segmentation manages biochemical network complexity while enabling efficient C6 building block production

Inventive Principle:

Principle #1Segmentation

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 efficient production of C6 building blocks by redirecting carbon flux and attenuating the host's biochemical network, overcoming the optimality principle and achieving high yields of adipic acid, caprolactam, 6-aminohexanoic acid, 6-hydroxyhexanoic acid, hexamethylenediamine, and 1,6-hexanediol.