Corynebacterium Metabolic Engineering for Organic Compound Yield

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Biorefinery processes for producing organic compounds from biomass-derived saccharides have lower productivity compared to petroleum refinery methods, necessitating improvements in saccharide metabolism pathways to enhance the efficiency and yield of organic compound production.

Innovation Solution

Introduction of the Entner-Doudoroff pathway into coryneform bacteria, specifically by encoding genes for glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydratase, and 2-keto-3-deoxy-6-phosphogluconate aldolase activities, allowing for the combination of the Embden-Meyerhof-Parnas and Entner-Doudoroff pathways to improve saccharide metabolism and organic compound production.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If biorefinery processes use conventional saccharide metabolism pathways (EMP pathway), then the process is simpler to implement, but the productivity and conversion rate of organic compounds are lower

Engineering Contradiction:
Improveproductivity of organic compound productionVSAvoidcomplexity of metabolic pathway
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent combines the Embden-Meyerhof-Parnas (EMP) pathway and the Entner-Doudoroff (ED) pathway in a single coryneform bacterium host. This merging of two metabolic pathways allows the organism to utilize multiple routes for saccharide degradation, thereby increasing the overall conversion rate and productivity of organic compounds while maintaining the simplicity of using a single host organism

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The coryneform bacterium is engineered to perform multiple functions by simultaneously possessing both EMP and ED pathways. This multi-functionality enables the organism to metabolize saccharides through either pathway or both in parallel, increasing flexibility and productivity without requiring multiple separate biorefinery processes

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Quantity of substance

If the Entner-Doudoroff pathway is introduced into coryneform bacteria, then the conversion rate and yield of organic compounds are enhanced, but the genetic engineering complexity increases

Engineering Contradiction:
Improveyield of organic compoundVSAvoidease of genetic modification
Core Design Contradiction:
Quantity of substanceVSEase of manufacture

Solution Approach 1:

The patent introduces the ED pathway into coryneform bacteria that already possess the EMP pathway, merging both pathways in a single organism. This approach achieves enhanced organic compound yield through multiple metabolic routes while utilizing a well-established host system with available genetic tools, thereby balancing the complexity of genetic modification with the benefit of improved productivity

Inventive Principle:
Principle #5Merging (Combining)

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 enhances the conversion rate and yield of organic compounds, improving productivity in coryneform bacteria that originally lack the Entner-Doudoroff pathway, thereby addressing the productivity limitations of biorefinery methods.

Implementation Method 1

glucose-6-phosphate dehydrogenase (hereinafter abbreviated as 'G6DH') that converts glucose-6-phosphate into 6-phosphoglucono-1,5-lactone

Methodology Applied
Scientific EffectOxidation: Oxidation

Implementation Method 2

6-phosphogluconate dehydratase (hereinafter abbreviated as 'EDD') that catalyzes a reaction of conversion from 6-phosphogluconate into 2-keto-3-deoxy-6-phosphogluconate

Methodology Applied
Scientific EffectDehydration:

Implementation Method 3

2-keto-3-deoxy-6-phosphogluconate aldolase (hereinafter abbreviated as 'EDA') as an enzyme that cleaves 2-keto-3-deoxy-6-phosphogluconate so as to produce glyceraldehyde-3-phosphate and pyruvate

Methodology Applied
Scientific EffectAldol cleavage:

Implementation Method 4

It is said that the saccharide metabolism through the ED pathway has a low efficiency in the production of ATP, and to compensate it, the rate of saccharide metabolism through the ED pathway is greater than that through the EMP pathway

Methodology Applied
Scientific EffectFermentation: Fermentation

Data Source

PatentUS11459574B2Transformant having Entner-Doudoroff pathway and production method for organic compound using same
Publication Date: 2022.10.04 RES INST OF INNOVATIVE TECH FOR THE EARTH

AI summary

Provided is a method for improving productivity in producing an organic compound in a bacterium that originally does not have an inherent ED pathway. In one aspect, provided is a transformant of a coryneform bacterium that is obtained by introducing the Entner-Doudoroff pathway into the coryneform bacterium as a host. In another aspect, provided is a transformant of a coryneform bacterium that is obtained by introducing, into a coryneform bacterium as a host a gene in which an enzyme having glucose-6-phosphate dehydrogenase activity is encoded, a gene in which an enzyme having 6-phosphogluconate dehydratase activity is encoded, and a gene in which an enzyme having 2-keto-3-deoxy-6-phosphogluconate aldolase activity is encoded.