Recombinant E. coli ATP Optimization via FhuCDB Gene Deletion

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Solution Overview

Problem

Microorganisms used for producing L-amino acids face challenges in maintaining sufficient intracellular energy levels, particularly ATP, which is crucial for biosynthesis and metabolic activities, due to high ATP demand and inefficient iron uptake processes.

Innovation Solution

Inactivating the FhuCDB protein complex in E. coli by deleting the fhuC, fhuD, and fhuB genes to reduce ATP consumption during iron uptake, thereby increasing intracellular ATP levels and enhancing the production of L-amino acids like L-threonine and L-tryptophan.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If iron uptake via FhuCDB protein complex is enhanced, then iron homeostasis is improved, but intracellular ATP level decreases due to high energy consumption

Engineering Contradiction:

Improveiron homeostasisVSAvoidintracellular ATP level

Core Design Contradiction:

ReliabilityVSUse of energy by moving object

Solution Approach 1:

The patent removes the FhuCDB iron uptake pathway from the E. coli system by deleting the fhuC, fhuD, and fhuB genes. This extraction eliminates the energy-consuming iron uptake mechanism while maintaining iron homeostasis through alternative pathways, thereby resolving the contradiction between reliable iron uptake and ATP conservation

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the operational state of the FhuCDB protein complex from active to inactive by gene deletion. This parameter change (from functional to non-functional) eliminates ATP consumption associated with this pathway while allowing the cell to maintain iron homeostasis through other mechanisms

Inventive Principle:

Principle #35Parameter changes

2Quantity of substance

If FhuCDB protein complex is active for iron uptake, then iron absorption is improved, but L-amino acid production efficiency decreases due to ATP depletion

Engineering Contradiction:

Improveiron uptakeVSAvoidL-amino acid production efficiency

Core Design Contradiction:

Quantity of substanceVSProductivity

Solution Approach 1:

By extracting/removing the FhuCDB iron uptake pathway through gene deletion, the patent eliminates the ATP consumption that was limiting L-amino acid production. The cell reallocates energy resources from iron uptake to amino acid biosynthesis, improving productivity

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent enables the E. coli cell to serve itself by maintaining iron homeostasis through alternative pathways that do not deplete ATP reserves needed for L-amino acid production. The cell self-regulates energy distribution to prioritize product synthesis

Inventive Principle:

Principle #25Self-service

3Productivity

If high ATP demand is met for biosynthesis activities, then production capacity increases, but energy depletion occurs reducing cell viability

Engineering Contradiction:

Improvebiosynthesis capacityVSAvoidintracellular energy level

Core Design Contradiction:

ProductivityVSUse of energy by moving object

Solution Approach 1:

The patent converts the harmful effect of ATP depletion caused by FhuCDB activity into a benefit by eliminating this pathway. The ATP that would have been consumed by iron uptake is now available for biosynthesis, transforming an energy drain into an energy source for product production

Inventive Principle:

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

Data Source

PatentEP3147351B1Microorganism having improved intracellular energy level and method for producing l-amino acid using same

Publication Date: 2019.08.28 CJ CHEILJEDANG CORP

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AI summary

The present application relates to a recombinant microorganism having an improved intracellular energy level and a method for producing L-amino acid using the microorganism.