Microbial Production of Adipic Acid via Enzymatic Aldol Addition

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current methods for producing industrially important chemicals like adipic acid, hexamethylenediamine, and linear fatty acids and alcohols are not efficient and often rely on non-renewable sources, limiting their yield and sustainability.

Innovation Solution

The development of novel methods involving enzymatic and chemical steps using non-naturally occurring microbial organisms to convert CN aldehydes and pyruvate into β-hydroxyketone intermediates, which are then processed to produce compounds such as 1-butanol, adipic acid, and linear fatty acids and alcohols, utilizing renewable sources.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional methods are used to produce adipic acid, hexamethylenediamine, and linear fatty acids and alcohols, then production can be maintained, but yield is low and sustainability is poor

Engineering Contradiction:
ImproveyieldVSAvoidsustainability
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent changes the fundamental parameters of the production process by using enzymatic catalysis instead of conventional chemical methods, and by using renewable carbon sources (glycerol, sugars) instead of petrochemical feedstocks. This transforms both the reaction conditions and the feedstock composition, achieving high yield while improving sustainability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent replaces conventional chemical catalysis and mechanical processing with enzymatic catalysis. Enzymes such as aldolases, dehydratases, and reductases are used to catalyze the conversion of carbon sources to target chemicals, providing a more sustainable and efficient alternative to traditional chemical methods.

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

2Productivity

If conventional chemical methods are used, then production processes are established, but they are not efficient and rely on non-renewable sources

Engineering Contradiction:
ImproveefficiencyVSAvoidprocess complexity
Core Design Contradiction:
ProductivityVSEase of manufacture

Solution Approach 1:

The patent uses β-hydroxyketone intermediates as key intermediaries in the conversion pathway from carbon sources to target chemicals. These intermediates are formed through enzymatic aldol condensation and serve as central nodes in the metabolic pathway, enabling efficient conversion while maintaining processability.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent divides the production process into distinct enzymatic steps: aldol condensation to form β-hydroxyketones, dehydration to form α,β-unsaturated carbonyls, and reduction to form final products. This segmentation allows each step to be optimized independently with specific enzymes, improving overall efficiency.

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 high-yield production of these chemicals using renewable sources, enhancing sustainability and efficiency in industrial processes.

Implementation Method 1

combining or incubating a CN aldehyde and a pyruvate in a solution under conditions that (a) convert the CN aldehyde and the pyruvate to a CN+3 β-hydroxyketone intermediate through an aldol addition

Methodology Applied
Scientific EffectAldol addition: Chemical Bonding

Implementation Method 2

convert the CN+3 β-hydroxyketone intermediate to the compound through enzymatic steps or a combination of enzymatic and chemical steps

Methodology Applied
Scientific EffectEnzymatic catalysis: Enzyme

Data Source

PatentUS12104160B2Production of 4,6-dihydroxy-2-oxo-hexanoic acid
Publication Date: 2024.10.01 ZYMOCHEM INC
  • US12104160B2 patent drawing
  • US12104160B2 patent drawing
  • US12104160B2 patent drawing

AI summary

Provided herein are methods, compositions, and non-naturally occurring microbial organism for preparing compounds such as1-butanol, butyric acid, succinic acid, 1,4-butanediol, 1-pentanol, pentanoic acid, glutaric acid, 1,5-pentanediol, 1-hexanol, hexanoic acid, adipic acid, 1,6-hexanediol, 6-hydroxy hexanoic acid, ε-Caprolactone, 6-amino-hexanoic acid, ε-Caprolactam, hexamethylenediamine, linear fatty acids and linear fatty alcohols that are between 7-25 carbons long, linear alkanes and linear α-alkenes that are between 6-24 carbons long, sebacic acid and dodecanedioic acid comprising: a) converting a CN aldehyde and pyruvate to a CN+3 β-hydroxyketone intermediate through an aldol addition; and b) converting the CN+3 β-hydroxyketone intermediate to the compounds through enzymatic steps, or a combination of enzymatic and chemical steps.