Microorganism PdhR Suppression for C6 Compound Production

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Solution Overview

Problem

Current methods for producing C6 compounds using microorganisms face inefficiencies in productivity and by-product formation, which hinder industrial application, as existing genetic modifications primarily focus on enzyme-related reactions rather than transcription factor control.

Innovation Solution

A modified microorganism with a genetic modification that suppresses the transcription factor controlling pyruvate dehydrogenase expression is developed, enhancing C6 compound production and reducing valine by-product accumulation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If genetic modification focuses on enzyme-related reactions, then C6 compound production pathway is established, but productivity is insufficient for industrial use

Engineering Contradiction:

ImproveC6 compound production abilityVSAvoidgenetic modification complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The invention extracts and targets the specific transcription factor (PdhR) that controls pyruvate dehydrogenase expression, separating the control mechanism from the metabolic pathway itself. By disrupting only this single transcription factor gene rather than modifying multiple enzyme genes, the invention simplifies the genetic modification approach while achieving improved C6 compound productivity.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The invention changes the regulatory parameter of pyruvate dehydrogenase expression by suppressing its transcription factor PdhR. This parameter change in gene expression control leads to altered metabolic flux toward C6 compound production, improving productivity without requiring complex multi-gene modifications.

Inventive Principle:

Principle #35Parameter changes

2Quantity of substance

If microorganisms produce target compounds through fermentation, then renewable raw materials are used, but by-products are produced which decrease yield and increase separation cost

Engineering Contradiction:

Improvetarget compound yieldVSAvoidby-product formation

Core Design Contradiction:

Quantity of substanceVSObject-generated harmful factors

Solution Approach 1:

The invention converts the potentially harmful by-product formation into a benefit by strategically suppressing the transcription factor that leads to by-products. By disrupting PdhR, the invention redirects metabolic flux away from by-product pathways (such as valine production) and toward the desired C6 compound pathway, effectively using genetic suppression to eliminate harmful side reactions.

Inventive Principle:

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

Solution Approach 2:

The invention applies preliminary anti-action by preemptively suppressing the transcription factor PdhR before by-products can form. This preventive genetic modification stops the metabolic pathway that would lead to by-products at the transcriptional level, preventing the harmful effect before it occurs and maximizing target compound yield.

Inventive Principle:

Principle #9Preliminary anti-action

Data Source

PatentUS20230227865A1Modified Microorganisms and Production Method of Compounds

Publication Date: 2023.07.20 ASAHI KASEI KOGYO KABUSHIKI KAISHA

AI summary

A modified microorganism containing a genetic modification that suppresses a transcription factor that controls expression of pyruvate dehydrogenase, in which the microorganism has and a production pathway of a C6 compound, and in which the C6 compound is at least one compound selected from the group consisting of adipic acid, hexamethylenediamine, 1,6-hexanediol, 6-aminohexanoic acid, 6-amino-1-hexanol, 6-hydroxyhexanoic acid, 3-oxoadipic acid, 3-hydroxyadipic acid, and 2,3-dehydroadipic acid.