Enzyme-Modified Submerged Fermentation Broth Viscosity

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Solution Overview

Problem

High viscosity in submerged fermentation broths leads to inefficient mixing, spatial variations in fermentation parameters, reduced mass transfer rates, and decreased productivity and yield due to impaired oxygen and carbon dioxide transfer.

Innovation Solution

Adding at least one enzyme, such as muramidase, chitinase, glucanase, or phosphodiesterase, to the fermentation broth to reduce viscosity, which can be achieved by co-expressing the enzyme in the microorganism or adding it directly to the broth.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If agitation speed is increased to maintain oxygen transfer rate when viscosity increases, then oxygen transfer rate is maintained, but power consumption and mechanical stress increase

Engineering Contradiction:
Improveoxygen transfer rateVSAvoidpower consumption
Core Design Contradiction:
ReliabilityVSUse of energy by moving object

Solution Approach 1:

The invention changes the physical-chemical parameters of the fermentation broth by adding enzymes (muramidase, chitinase, glucanase, or phosphodiesterase) that degrade polysaccharides and reduce viscosity. This parameter change allows maintaining oxygen transfer rate at lower agitation speeds, thereby reducing power consumption while ensuring adequate oxygen supply to microorganisms

Inventive Principle:
Principle #35Parameter changes

2Stability of the object's composition

If agitation speed is increased to improve mixing when viscosity increases, then mixing efficiency is improved, but mechanical stress on cells and equipment increases

Engineering Contradiction:
Improvemixing efficiencyVSAvoidmechanical stress
Core Design Contradiction:
Stability of the object's compositionVSStrength

Solution Approach 1:

By adding enzymes that reduce broth viscosity through degradation of polysaccharides, the invention changes the rheological parameters of the fermentation medium. This enables effective mixing at lower agitation speeds, reducing mechanical stress on microbial cells and equipment while maintaining homogeneous distribution of nutrients and cells

Inventive Principle:
Principle #35Parameter changes

3Reliability

If viscosity is reduced by enzyme addition, then mass transfer rates improve, but process complexity increases

Engineering Contradiction:
Improvemass transfer rateVSAvoidprocess complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The invention employs the microorganisms' own metabolic byproducts (polysaccharides) as the target for viscosity reduction. Enzymes added to the system selectively degrade these polysaccharides, allowing the fermentation process itself to generate the substrate that, when modified, improves mass transfer. This self-service approach enhances mass transfer without requiring external intervention beyond enzyme addition

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

Enzymes serve as intermediary substances that mediate between the fermentation broth's natural polysaccharide content and the desired viscosity reduction. These biological catalysts specifically target polysaccharide degradation, providing a selective and controllable mechanism to improve mass transfer rates while maintaining process simplicity through bio-based intervention

Inventive Principle:
Principle #24Intermediary (Mediator)

4Quantity of substance

If viscosity is high, then cell growth may be maintained, but productivity and yield decrease due to reduced mass transfer

Engineering Contradiction:
Improvecell growthVSAvoidproductivity and yield
Core Design Contradiction:
Quantity of substanceVSProductivity

Solution Approach 1:

The invention changes the viscosity parameter of the fermentation broth by adding enzymes that degrade polysaccharides. This parameter modification simultaneously improves mass transfer rates for oxygen and carbon dioxide, enabling higher productivity and yield while maintaining adequate cell growth conditions. The enzyme addition creates an optimal balance between cell maintenance and product formation

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

The reduction in viscosity improves liquid mixing, reduces spatial variations in fermentation parameters, enhances oxygen uptake and carbon dioxide removal, leading to increased productivity and yield.

Implementation Method 1

adding at least one enzyme, preferably comprising a muramidase, a chitinase, a glucanase or a phosphodiesterase

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 2

The addition of at least one enzyme... resulted in a reduced viscosity

Methodology Applied
Scientific EffectHydrolysis: Hydrolysis

Data Source

PatentUS20250197909A1Submerged fermentation process
Publication Date: 2025.06.19 NOVOZYMES AS
  • US20250197909A1 patent drawing

AI summary

The present invention provides submerged fermentation processes of producing one or more polypeptide of interest, the process comprising: a) fermenting one or more microorganism that produces the one more polypeptide of interest in a fermentation broth, and b) adding at least one enzyme to the fermentation broth: OR co-expressing the at least one enzyme in the one or more microorganism and secreting the at least one enzyme into the fermentation broth in an amount sufficient to reduce the viscosity of the fermentation broth, compared to when the at least one enzyme is not added or co-expressed; and, optionally, c) recovering the one or more polypeptide of interest.