2-Hydroxyacyl-CoA Pathways Using Formyl-CoA Acyloin Condensation

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Solution Overview

Problem

Existing methods for chemical production using one-carbon substrates are limited by the need to first produce two or three carbon metabolites, restricting the range of products that can be derived from unsubstituted/non-functionalized 2-hydroxyacyl-CoA intermediates.

Innovation Solution

Employing enzyme combinations and recombinant microbes to catalyze acyloin condensation reactions between formyl-CoA and functionalized aldehydes or ketones, producing substituted/functionalized 2-hydroxyacyl-CoAs, which can then be converted into a variety of industrial chemicals through metabolic pathways.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If existing methods for chemical production using one-carbon substrates are used, then two or three carbon metabolites must be produced first, but this restricts the range of products that can be derived

Engineering Contradiction:

Improverange of productsVSAvoidproduction process complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The invention segments the production process into distinct enzymatic steps: formyl-CoA generation from one-carbon substrates, followed by acyloin condensation with functionalized aldehydes or ketones to produce substituted 2-hydroxyacyl-CoAs, which can then be converted to diverse products. This segmentation allows direct utilization of one-carbon substrates without requiring intermediate two or three carbon metabolite production, thereby expanding product range while maintaining process manageability

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention introduces substituted 2-hydroxyacyl-CoA as a key intermediary compound that bridges one-carbon substrates and diverse industrial chemicals. This intermediary enables direct one-carbon to multi-carbon conversion through controlled enzymatic reactions, eliminating the need for traditional two or three carbon metabolite intermediates and expanding the versatility of product derivation

Inventive Principle:

Principle #24Intermediary (Mediator)

2Adaptability or versatility

If unsubstituted/non-functionalized 2-hydroxyacyl-CoA intermediates are used, then the production process is simpler, but the range of derivable products is limited

Engineering Contradiction:

Improveproduct diversityVSAvoidmanufacturing simplicity

Core Design Contradiction:

Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The invention applies local quality by introducing specific functional groups (substituents) at particular positions on the 2-hydroxyacyl-CoA intermediate through selective acyloin condensation reactions with functionalized aldehydes or ketones. This localized functionalization enables diverse product derivation from the intermediate while maintaining controlled and manageable manufacturing processes through specific enzymatic reactions

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The invention changes the chemical parameters of the 2-hydroxyacyl-CoA intermediate by producing substituted/functionalized variants with different carbon chain lengths, functional groups, and molecular structures. These parameter changes expand the range of derivable products while the enzymatic nature of the reactions maintains manufacturing simplicity and biological compatibility

Inventive Principle:

Principle #35Parameter changes

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

Enables the production of a diverse range of chemical products, including poly-hydroxylated molecules, polyols, and polyhydroxycarboxylic acids, directly from one-carbon substrates, enhancing the versatility and efficiency of chemical synthesis.

Implementation Method 1

Employing enzyme combinations and recombinant microbes to catalyze acyloin condensation reactions between formyl-CoA and functionalized aldehydes or ketones

Methodology Applied

Scientific EffectEnzyme catalysis: Enzyme

Data Source

PatentUS20250361541A1Production of 2-Hydroxyacyl-CoAs and Derivatives Thereof

Publication Date: 2025.11.27 MOJIA BIOTECH PTE LTD

AI summary

The production of substituted 2-hydroxyacyl-CoA molecules by a novel reaction is described. The reaction involves the condensation of formyl-CoA with a carbonyl-containing molecule. Such carbonyl-containing molecules include a substituted aldehyde and a ketone. The reaction is catalyzed by enzymes using a TPP-dependent mechanism. Also described is the production of unsubstituted and substituted 2-hydroxyacyl-CoA molecules comprising the condensation of formyl-CoA with a carbonyl-containing molecule, wherein the condensation is catalyzed by a prokaryotic HACL. The 2-hydroxyacyl-CoA can be converted to chemical products having broad applications by using enzyme catalysts. The combination of enzyme catalysts comprises novel biochemical reaction pathways that can be deployed either as polypeptides in a reaction buffer or genetically encoded in recombinant microorganisms.