ClpB Chaperone Expression for Stress-Resilient PHA Production

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Solution Overview

Problem

The production cost of polyhydroxyalkanoates (PHAs) remains high due to low productivity, and there is a need to enhance their industrial applicability as biodegradable plastics.

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 remains high due to low productivity

Engineering Contradiction:

ImprovePHA productivityVSAvoidproduction cost

Core Design Contradiction:

ProductivityVSEase of manufacture

Solution Approach 1:

The invention changes the biological parameter of the microorganism by introducing or enhancing chaperone genes (GroESL, DnaKJ, ClpB) to improve protein folding efficiency under stress conditions, thereby increasing PHA productivity and reducing production cost

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

Chaperone proteins act as intermediaries that facilitate proper protein folding and prevent aggregation during PHA production, especially under stress conditions, thereby improving overall productivity without changing the fundamental PHA synthesis pathway

Inventive Principle:

Principle #24Intermediary (Mediator)

2Productivity

If chaperone GroESL is overexpressed in Cupriavidus necator, then isopropanol productivity increases by 9 to 18%, but the impact on polyhydroxyalkanoate productivity remains unexplored

Engineering Contradiction:

Improveisopropanol productivityVSAvoidimpact on PHA productivity

Core Design Contradiction:

ProductivityVSLoss of information

Solution Approach 1:

The invention demonstrates that chaperone systems have universal functionality across different metabolic pathways, showing that overexpression of chaperone genes not only increases isopropanol productivity but also significantly enhances PHA productivity, revealing the multi-functional nature of chaperone proteins in different biosynthetic pathways

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Object-affected harmful factors

If proteins are misfolded due to stress such as heat or oxidative stress, then protein aggregation occurs, but chaperones can unfold misfolded proteins and assist refolding

Engineering Contradiction:

Improveprotein aggregationVSAvoidprotein conformational structure

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The invention converts the harmful effect of stress-induced protein misfolding and aggregation into a beneficial outcome by utilizing chaperone proteins that specifically recognize and resolve misfolded states, thereby improving overall system reliability and PHA productivity under stress conditions

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

Chaperone proteins serve as intermediary molecules that intervene between stress factors and target proteins, preventing harmful aggregation and facilitating proper folding, thereby protecting the integrity of PHA synthesis enzymes and other critical proteins

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentEP4663747A1Transformed microorganism, and method for producing polyhydroxyalkanoic acid

Publication Date: 2025.12.17 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.