ClpB Chaperone Engineering for Higher PHA Productivity

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Solution Overview

Problem

The production cost of biodegradable polyhydroxyalkanoates (PHAs) is high due to low productivity, and there is a need to enhance their production efficiency.

Innovation Solution

Introduce a gene encoding a chaperone belonging to the ClpB family or enhance its expression in a microorganism with polyhydroxyalkanoate-producing ability, specifically in bacteria like Cupriavidus necator, to increase PHA productivity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional PHA production methods are used, then PHA can be produced as a biodegradable plastic, but the production cost is high due to low productivity

Engineering Contradiction:
ImprovePHA productivityVSAvoidproduction cost
Core Design Contradiction:
ProductivityVSEase of manufacture

Solution Approach 1:

The patent changes the biological parameter of the microorganism by introducing foreign genes (polyhydroxyalkanoate synthase gene from Aeromonas caviae and chaperone gene from Escherichia coli) to alter the PHA production pathway and protein folding efficiency, thereby increasing productivity without proportionally increasing production cost

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces a chaperone protein as an intermediary substance that mediates between the synthesized PHA and the cellular environment, facilitating proper protein folding and preventing aggregation, which indirectly enhances PHA production efficiency and reduces overall production costs

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If chaperone GroESL is overexpressed to increase isopropanol productivity, then isopropanol productivity increases by 9 to 18%, but there is no reported impact on polyhydroxyalkanoate productivity

Engineering Contradiction:
Improveisopropanol productivityVSAvoidimpact on PHA productivity
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

Instead of using the previously tested chaperone GroESL for PHA production, the patent inverts the approach by selecting a different chaperone system (ClpB family from E. coli) that has not been previously evaluated for PHA production, thereby discovering a new effective combination for enhancing PHA productivity

Inventive Principle:
Principle #13The other way round (Inversion)

3Productivity

If a gene encoding a chaperone belonging to the ClpB family is introduced or its expression is enhanced, then polyhydroxyalkanoate productivity increases, but the device complexity increases

Engineering Contradiction:
Improvepolyhydroxyalkanoate productivityVSAvoidgenetic engineering complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent segments the genetic engineering process into distinct functional modules: a polyhydroxyalkanoate synthase gene for PHA synthesis and a chaperone gene for protein folding assistance. This modular approach allows independent optimization of each function while managing the overall genetic complexity

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

The transformed microorganism achieves high polyhydroxyalkanoate productivity even under stress conditions, reducing production costs and enhancing PHA accumulation.

Implementation Method 1

Chaperone ClpB functions to unfold and disaggregate aggregated proteins

Methodology Applied
Scientific EffectProtein disaggregation:

Implementation Method 2

polyhydroxyalkanoate synthase gene; a gene encoding a chaperone belonging to the ClpB family

Methodology Applied
Scientific EffectBiological synthesis:

Data Source

PatentUS20260035720A1Transformed microorganism and polyhydroxyalkanoate production method
Publication Date: 2026.02.05 KANEKA CORP

AI summary

A transformed microorganism having an ability to produce a polyhydroxyalkanoate includes a polyhydroxyalkanoate synthase gene and a gene encoding a chaperone belonging to the ClpB family. The gene encoding the chaperone belonging to the ClpB family is a gene which has been introduced into the transformed microorganism or whose expression has been enhanced in the transformed microorganism. The chaperone belonging to the ClpB family may be derived from the genus Cupriavidus, Escherichia, or Saccharomyces. A polyhydroxyalkanoate can be produced by culturing the transformed microorganism.