Fed-Batch 3-HP Production From Glycerol Without Substrate Inhibition

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Solution Overview

Problem

Existing methods for producing 3-hydroxypropionic acid (3-HP) face challenges of low yield and productivity, particularly in biotechnological processes, and there is a need for improved methods to enhance the concentration and efficiency of 3-HP production from glycerol.

Innovation Solution

A method involving high-concentration cell culturing strains in a growth medium without glycerol, followed by a fed-batch process in a production medium with controlled glycerol addition, allowing for high-concentration and high-productivity 3-HP production by maintaining substrate inhibition and optimal production conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If biotechnological production method is used for 3-HP, then environmental friendliness is improved, but yield and productivity deteriorate

Engineering Contradiction:
Improveenvironmental friendlinessVSAvoidyield and productivity
Core Design Contradiction:
Object-affected harmful factorsVSProductivity

Solution Approach 1:

The production process is divided into two distinct stages: a growth stage where cells are cultivated in a growth medium without glycerol, and a production stage where cells convert substrate to 3-HP in a production medium with glycerol. This segmentation allows optimization of each stage independently, achieving both high cell density and high productivity while maintaining environmental benefits of biotechnological production.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Cells are pre-cultured to high concentration in the growth stage before being transferred to the production stage. This preliminary action of building up cell density beforehand enables the production stage to achieve high productivity without requiring high initial substrate concentrations that would cause inhibition.

Inventive Principle:
Principle #10Preliminary action

2Quantity of substance

If high concentration of glycerol is used in production medium, then substrate utilization is improved, but substrate inhibition occurs

Engineering Contradiction:
Improveglycerol concentrationVSAvoidsubstrate inhibition
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The use of glycerol is segmented into two phases: initially excluded during the growth stage to avoid inhibition, then introduced at optimized concentrations during the production stage when cells are already adapted. This temporal segmentation allows high glycerol utilization without suffering from substrate inhibition effects.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The glycerol concentration parameter is dynamically changed between stages: zero glycerol during growth, then optimized glycerol concentration during production. This parameter change allows the system to achieve high substrate utilization efficiency while avoiding the harmful effects of high glycerol concentration on cell metabolism.

Inventive Principle:
Principle #35Parameter changes

3Productivity

If fed-batch process with additional glycerol supply is used, then productivity is improved, but process complexity increases

Engineering Contradiction:
Improve3-HP productivityVSAvoidprocess complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The fed-batch process with additional glycerol supply is segmented into the two-stage process (growth stage without glycerol, production stage with glycerol). This segmentation simplifies control by establishing clear rules for when to add glycerol, reducing process complexity while maintaining high productivity through optimized substrate feeding.

Inventive Principle:
Principle #1Segmentation

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

The method achieves high-concentration and high-yield 3-HP production, reducing raw material and operational costs by effectively consuming glycerol and minimizing by-product formation, thus enhancing overall production efficiency.

Implementation Method 1

producing (converting) 3-HP by transferring the culture solution of the above step into a production medium comprising a substrate, and the producing is performed by a fed-batch process

Methodology Applied
Scientific EffectFermentation: Fermentation

Data Source

PatentEP4722374A1Method for producing 3-hydroxypropionic acid
Publication Date: 2026.04.08 LG CHEM LTD
  • EP4722374A1 patent drawingFigure 1
  • EP4722374A1 patent drawingFigure 2
  • EP4722374A1 patent drawingFigure 3

AI summary

The present invention relates to a method for preparing 3-HP and/or improving productivity of 3-HP by culturing cells at a high concentration and adjusting the concentration of initial glycerol and the concentration of additional glycerol and the addition time, while producing and culturing this high-concentration cell culture solution by fed-batch culture, and can produce a high concentration of 3HP from a high concentration of glycerol.