PHA Production via Coenzyme A-Dependent Aldehyde Dehydrogenase Pathways

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Solution Overview

Problem

Current methods for producing polyhydroxyalkanoate (PHA) polymers containing 3-hydroxyvalerate (3HV) units are limited by the need for propionic acid in the feed, which is toxic to cells and increases production costs due to its high expense and inefficient incorporation into the polymer.

Innovation Solution

Microbial strains engineered with genes encoding Coenzyme-A-dependent aldehyde dehydrogenase, acyl-CoA transferase, acyl-CoA synthetase, β-ketothiolase, and PHA synthase convert alcohols to 3-hydroxyacyl-CoA monomers, bypassing the need for propionic acid, thereby producing PHA polymers with higher productivities and yields.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If propionic acid is used as a co-feed to produce PHA copolymers containing 3HV units, then the polymer can be produced with higher 3HV content, but the toxicity to cells increases and production cost increases

Engineering Contradiction:
Improve3HV content in polymerVSAvoidtoxicity to cells
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The invention extracts and removes propionic acid from the feedstock, replacing it with 1-propanol as the carbon source. This eliminates the toxicity problem while maintaining the ability to produce 3HV-containing PHA copolymers through the metabolic conversion of 1-propanol to propionyl-CoA and subsequently to 3-hydroxyvaleryl-CoA.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention changes the chemical parameter of the feedstock from propionic acid to 1-propanol. This parameter change transforms the toxic feedstock into a non-toxic alternative while maintaining the metabolic pathway capability to produce 3HV units through the action of alcohol dehydrogenase, aldehyde dehydrogenase, and CoA synthetase enzymes.

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If propionic acid is used as a co-feed to produce PHA copolymers containing 3HV units, then the polymer can be produced with higher 3HV content, but the production cost increases due to high expense and inefficient incorporation

Engineering Contradiction:
Improve3HV content in polymerVSAvoidproduction cost
Core Design Contradiction:
Quantity of substanceVSEase of manufacture

Solution Approach 1:

The invention extracts and removes propionic acid from the feedstock, replacing it with 1-propanol as the carbon source. This eliminates the toxicity problem while maintaining the ability to produce 3HV-containing PHA copolymers through the metabolic conversion of 1-propanol to propionyl-CoA and subsequently to 3-hydroxyvaleryl-CoA.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention changes the chemical parameter of the feedstock from propionic acid to 1-propanol. This parameter change transforms the toxic feedstock into a non-toxic alternative while maintaining the metabolic pathway capability to produce 3HV units through the action of alcohol dehydrogenase, aldehyde dehydrogenase, and CoA synthetase enzymes.

Inventive Principle:
Principle #35Parameter changes

3Quantity of substance

If propionic acid is used as a co-feed, then 3HV copolymers can be produced, but the rate of growth and polymer production decreases due to toxicity

Engineering Contradiction:
Improve3HV content in polymerVSAvoidrate of growth and polymer production
Core Design Contradiction:
Quantity of substanceVSProductivity

Solution Approach 1:

The invention extracts and removes propionic acid from the feedstock, replacing it with 1-propanol as the carbon source. This eliminates the toxicity problem while maintaining the ability to produce 3HV-containing PHA copolymers through the metabolic conversion of 1-propanol to propionyl-CoA and subsequently to 3-hydroxyvaleryl-CoA.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention changes the chemical parameter of the feedstock from propionic acid to 1-propanol. This parameter change transforms the toxic feedstock into a non-toxic alternative while maintaining the metabolic pathway capability to produce 3HV units through the action of alcohol dehydrogenase, aldehyde dehydrogenase, and CoA synthetase enzymes.

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

This approach allows for the production of PHA polymers with higher 3HV content without the use of propionic acid, reducing toxicity and production costs, and improving the efficiency of 3HV incorporation into the polymer.

Implementation Method 1

at least one step in the conversion pathway involves a Co-enzyme A-dependent aldehyde dehydrogenase activity

Methodology Applied
Scientific EffectOxidation: Oxidation

Implementation Method 2

the enzyme-catalyzed conversion of alcohols to 3-hydroxyacyl-CoA monomers

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Data Source

PatentUS8071355B2Polyhydroxyalkanoate production by coenzyme A-dependent aldehyde dehydrogenase pathways
Publication Date: 2011.12.06 CJ CHEILJEDANG CORP
  • US8071355B2 patent drawing
  • US8071355B2 patent drawing

AI summary

Organisms are provided containing genes encoding one or more enzymes, Coenzyme-A-dependent aldehyde dehydrogenase, acyl-CoA transferase, acyl-CoA synthetase, β-ketothiolase, acetoacetyl-CoA reductase and/or PHA synthase. In some cases one or more of these genes are native to the host organism and the remainder are heterologous genes provided by genetic engineering. These organisms produce poly (3-hydroxyalkanoate) homopolymers or co-polymers comprising 3-hydroxalkanoate monomers other than 3-hydroxybutryrate wherein these 3-hydroxyalkanoate units are derived from the enzyme-catalyzed conversion of alcohols to 3-hydroxyacyl-CoA monomers, where at least one step in the conversion pathway involves a Co-enzyme A-dependent aldehyde dehydrogenase activity. The PHA polymers are readily recovered and industrially useful as polymers for articles such as films, latexes, coatings, adhesives, fibers, binders, resins, and medical devices.