Recombinant Yeast Lactic Acid Production via pH Shift

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Solution Overview

Problem

Current methods for producing lactic acid using lactic acid bacteria face challenges such as high production costs due to expensive purification processes, limited viability at low pH, and the need for organic nitrogen sources, which complicates the production of high-purity, optically pure isomers.

Innovation Solution

A two-step fermentation process using recombinant yeast strains engineered with lactate dehydrogenase (LDH) activity and decreased or knocked-out pyruvate decarboxylase (PDC) activity, where the yeast is cultivated at a pH of 5 to 7 for biomass production and then at a low pH for lactic acid production, allowing for efficient lactic acid yield and reduced fermentation time.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If lactic acid bacteria are used for lactic acid production, then the acid can be produced naturally, but the purification process becomes expensive and complex

Engineering Contradiction:
Improvenatural lactic acid productionVSAvoidpurification process cost and complexity
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent changes the pH parameter throughout the fermentation process. By maintaining high pH (7.0-9.0) during fermentation, lactic acid is produced in its ionized form which remains soluble and does not require acidification for purification. This parameter change eliminates the need for expensive acidification and salt removal steps required by conventional low-pH processes.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If lactic acid bacteria are used for lactic acid production, then production can proceed, but organic nitrogen sources are required which complicates the process

Engineering Contradiction:
Improvelactic acid productionVSAvoidprocess complexity due to organic nitrogen requirement
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent changes the pH parameter to alkaline conditions (7.0-9.0), which enables the use of inorganic nitrogen sources instead of organic nitrogen sources. This parameter change simplifies the medium composition and reduces process complexity while maintaining high lactic acid production efficiency.

Inventive Principle:
Principle #35Parameter changes

3Quantity of substance

If conventional fermentation processes are used, then lactic acid can be produced, but acidification and salt removal are required for purification

Engineering Contradiction:
Improvelactic acid productionVSAvoidpurification process steps
Core Design Contradiction:
Quantity of substanceVSEase of manufacture

Solution Approach 1:

The patent maintains alkaline pH (7.0-9.0) throughout the entire fermentation process, which keeps lactic acid in its ionized, soluble form. This eliminates the need for acidification and salt removal steps that are required in conventional low-pH processes, significantly simplifying the purification process while maintaining high lactic acid yield.

Inventive Principle:
Principle #35Parameter changes

4Productivity

If fermentation time is extended to increase lactic acid yield, then productivity improves, but exposure to stress conditions increases

Engineering Contradiction:
Improvelactic acid yieldVSAvoidstress condition exposure
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the pH parameter to alkaline conditions (7.0-9.0), which creates a less stressful environment for the microorganisms during fermentation. This allows for extended fermentation times to maximize lactic acid yield without subjecting the cells to prolonged acid stress, thereby maintaining cell viability and metabolic activity throughout the process.

Inventive Principle:
Principle #35Parameter changes

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 significantly reduces production costs, enhances productivity, and simplifies purification by avoiding the need for acidification and salt removal, resulting in high-purity lactic acid with reduced exposure to stress conditions.

Implementation Method 1

a yeast strain that is engineered to have lactate dehydrogenase (LDH) activity

Methodology Applied
Scientific EffectLactate dehydrogenase (LDH) activity: Enzyme

Implementation Method 2

a two-step fermentation process using recombinant yeast strains

Methodology Applied
Scientific EffectFermentation: Fermentation

Data Source

PatentUS10947571B2Method for producing lactic acid in recombinant yeast cell culture
Publication Date: 2021.03.16 SYCONIUM LACTIC ACID GMBH
  • US10947571B2 patent drawing
  • US10947571B2 patent drawing

AI summary

The present invention provides a method for producing lactic acid in a recombinant yeast cell culture using glucose as carbon source comprising a first, seed fermentation stage to produce biomass wherein the yeast is cultivated in a culture medium at a pH of 5 to 7, followed by a second, a production fermentation stage with biomass from the seed fermentation to produce lactic acid, wherein the yeast is cultivated in a culture medium at low p H using a yeast strain that is engineered to have lactate dehydrogenase (LDH) activity and optionally has decreased or knocked-out pyruvate decarboxylase (PDC) activity.