Yeast Cell Acid Tolerance via Gene Overexpression

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Solution Overview

Problem

Microorganisms lack acid tolerance, making them inactive and nonviable in acidic environments containing organic acids like lactic acid, which inhibits lactate production and industrial applications.

Innovation Solution

Genetically engineered yeast cells with increased activity of SUL1, STR3, HXT7, ERR1, GRX8, MXR1, GRE1, MRK1, or AAD10 are developed to enhance acid tolerance and lactate production by modifying gene expression and overexpressing specific genes, allowing them to thrive in acidic conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If microorganisms are used for lactate production, then lactate can be produced, but the microorganisms become inactive and nonviable under acidic environments

Engineering Contradiction:

Improvelactate productionVSAvoidmicroorganism viability

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent modifies the physiological parameters of yeast cells through genetic engineering to enhance their acid tolerance. Specific genes (SUL1, STR3, HXT7, ERR1, GRX8, MXR1, GRE1, MRK1, AAD10) are overexpressed to change the cell's response to acidic conditions, allowing the microorganisms to maintain viability and continue producing lactate in acidic environments where wild-type cells would become inactive

Inventive Principle:

Principle #35Parameter changes

2Productivity

If organic acid concentration is increased in extracellular environment, then lactate production is enhanced, but the free acid form permeates cell membrane and lowers intercellular pH

Engineering Contradiction:

Improvelactate productionVSAvoidintracellular pH reduction

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces copies of specific genes (SUL1, STR3, HXT7, ERR1, GRX8, MXR1, GRE1, MRK1, AAD10) into the yeast genome to create multiple copies that can be overexpressed. This genetic copying provides the cells with enhanced capacity to cope with acid stress, allowing them to tolerate higher extracellular organic acid concentrations that drive lactate production without suffering from intracellular pH collapse

Inventive Principle:

Principle #26Copying

3Reliability

If genetic modification is applied to increase acid tolerance, then yeast cells can survive in acidic environments, but the device complexity increases

Engineering Contradiction:

Improveacid toleranceVSAvoidgenetic engineering complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent selects genes that serve multiple functions: they are involved in both normal yeast metabolism and acid stress response. By overexpressing these multi-functional genes (SUL1 for sulfate transport, STR3 for sulfur metabolism, HXT7 for hexose transport, ERR1 for energy metabolism, GRX8 for redox balance, MXR1 for oxidative stress response, GRE1 for general stress response, MRK1 for protein phosphorylation, AAD10 for aldehyde metabolism), the yeast cells gain acid tolerance while maintaining their metabolic functions, avoiding the need for separate specialized systems

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS9994877B2Yeast cell having acid tolerance, method of preparing yeast cell and use thereof

Publication Date: 2018.06.12 SAMSUNG ELECTRONICS CO LTD

AI summary

Provided are a genetically engineered yeast cell having increased activity of SUL1, STR3, HXT7, ERR1, GRX8, MXR1, GRE1, MRK1, AAD10 or a combination thereof, compared to a parent cell, and also having acid tolerance, a method of preparing the same, and a method of producing lactate using the same.