L-Histidine Export Protein for Scalable Microbial Production

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Solution Overview

Problem

Existing methods for producing L-histidine are inefficient and environmentally polluting, and large-scale industrialization has not been achieved due to competition with phosphoribosyl pyrophosphate (PRPP) and complex biosynthesis processes.

Innovation Solution

A histidine export protein with specific L-histidine export ability is discovered and expressed in a microorganism, such as Corynebacterium or Escherichia, to enhance L-histidine production.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If microbial fermentation method is used to produce L-histidine, then production efficiency is improved compared to proteolytic extraction, but the process complexity and energy requirements increase due to competition with PRPP and complex biosynthesis regulation

Engineering Contradiction:

ImproveL-histidine production efficiencyVSAvoidbiosynthesis process complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent extracts and utilizes the specific function of the HisE protein (histidine export protein) from the complex biosynthesis system. By isolating and overexpressing this single protein component in host microorganisms, the system simplifies the overall process while maintaining high productivity, effectively separating the export function from the complex biosynthesis pathway.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent applies the HisE protein, originally discovered in Corynebacterium glutamicum, to multiple host microorganisms including E. coli and other bacteria. This universal export protein can function across different species, enabling the same protein to drive L-histidine production in various microbial systems without requiring species-specific optimization.

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Quantity of substance

If proteolytic extraction method using blood meal is used, then L-histidine production is achieved, but environmental pollution and low efficiency occur

Engineering Contradiction:

ImproveL-histidine production amountVSAvoidenvironmental pollution

Core Design Contradiction:

Quantity of substanceVSObject-generated harmful factors

Solution Approach 1:

The patent replaces the mechanical/chemical extraction process (proteolytic extraction using blood meal) with a biological production process (microbial fermentation). Instead of extracting L-histidine from animal by-products through chemical enzymes, the system uses genetically modified microorganisms to synthesize L-histidine biologically, eliminating the environmental pollution associated with blood meal processing while maintaining production capability.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Productivity

If HisE protein is overexpressed in microorganism, then L-histidine production is significantly improved, but the microorganism's natural biosynthesis regulation may be disrupted

Engineering Contradiction:

ImproveL-histidine production amountVSAvoidbiosynthesis regulation stability

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent segments the L-histidine production system into two independent functional components: (1) the biosynthesis pathway (which remains regulated and stable) and (2) the export function (which is enhanced by overexpressing HisE). By separating these functions, the system can optimize export capacity without disrupting the regulatory mechanisms of biosynthesis, maintaining reliability while improving productivity.

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS20250382647A1L-histidine export protein and method of producing l-histidine using same

Publication Date: 2025.12.18 CJ CHEILJEDANG CORP

AI summary

Provided are a novel protein having histidine exporting activity. an L-histidine producing microorganism modified to express the protein. and a L-histidine producing method using the microorganism.