Mutant L-Histidine Export Protein for Microbial Yield Improvement
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Solution Overview
Problem
Current methods for producing L-histidine are inefficient and environmentally polluting, and large-scale industrialization through microbial fermentation has not been achieved due to competition with phosphoribosyl pyrophosphate (PRPP) and complex biosynthesis processes.
Innovation Solution
Development of a mutant L-histidine export protein with enhanced activity, derived from Dermabacter vaginalis, and its expression in a microorganism to increase L-histidine production.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If protein hydrolysis extraction using blood meal is used to produce L-histidine, then L-histidine can be obtained as it is largely included in hemoglobin, but the production efficiency is low and environmental pollution occurs
Solution Approach 1:
The patent introduces a mutated L-histidine export protein (DvaE mutant with F92C mutation) that changes the export function of the microorganism. This parameter change in protein function enables efficient L-histidine secretion outside the cell, transforming the production system from intracellular accumulation to extracellular secretion, thereby dramatically improving production efficiency and enabling large-scale industrialization
2Productivity
If microbial fermentation is used to produce L-histidine, then a more efficient production method can be achieved, but large-scale industrialization has not been achieved due to competition with phosphoribosyl pyrophosphate (PRPP) and complex biosynthesis processes
Solution Approach 1:
The patent extracts the L-histidine export function from the complex biosynthesis system by introducing a heterologous L-histidine export protein (DvaE mutant). This separates the export function from the biosynthesis pathway, allowing L-histidine to be efficiently secreted without being constrained by the complex intracellular biosynthesis regulatory mechanisms, thereby enabling large-scale production
3Productivity
If the amino acid corresponding to the 92th residue of the amino acid sequence of SEQ ID NO: 13 is substituted with another amino acid, then L-histidine export activity is enhanced, but protein structure may be affected
Solution Approach 1:
The patent applies local quality change by introducing a specific point mutation (F92C) at position 92 of the DvaE protein. This localized amino acid substitution enhances L-histidine export activity while maintaining the overall protein structure stability, as the mutation is confined to a specific residue rather than affecting the entire protein structure
Data Source
AI summary
The present application discovers a histidine export protein having an ability to export L-histidine or a variant thereof, and expresses same in a microorganism having an ability to produce L-histidine, thereby dramatically improving L-histidine production.