Nisin Fermentation pH Control and Concentration

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Solution Overview

Problem

Conventional bacteriocin fermentation methods are inefficient for large-scale nisin production due to limited production rates and unsatisfactory final nisin concentrations, leading to high costs and challenges in producing stable, easy-to-use liquid or semi-liquid formulations that meet food safety and regulatory requirements.

Innovation Solution

A process involving a nutrient medium with a fermentable substrate and nitrogen source, inoculated with nisin-producing lactic acid bacteria, where the pH is controlled using alkaline potassium salts, and the fermentation broth is acidified and concentrated to produce a stable, high-lactate content liquid product with enhanced nisin activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional bacteriocin fermentation methods are used for large-scale nisin production, then production costs increase due to prolonged fermentation time, but nisin concentration and production rate remain insufficient

Engineering Contradiction:
Improvenisin production rateVSAvoidfermentation process duration
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The patent applies parameter changes by modifying fermentation conditions including pH control (maintaining pH 4.5-5.5), temperature (30-37°C), and nutrient composition (using defined medium with glucose, peptone, and yeast extract). These parameter optimizations enable faster nisin production rates while reducing fermentation time compared to conventional methods.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent implements feedback control through pH monitoring and adjustment during fermentation. The system continuously measures pH and adds alkaline substances (ammonium hydroxide or sodium hydroxide) to maintain optimal pH levels, ensuring consistent nisin production rates and preventing contamination risks associated with prolonged fermentation.

Inventive Principle:
Principle #23Feedback

2Quantity of substance

If fermentation is prolonged to increase nisin concentration, then contamination risk increases and production costs increase

Engineering Contradiction:
Improvenisin concentrationVSAvoidcontamination risk
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent uses feedback control through continuous pH monitoring to optimize fermentation time. By maintaining pH within 4.5-5.5 through controlled addition of alkaline substances, the system achieves high nisin concentration (≥1000 IU/ml) without requiring prolonged fermentation, thereby reducing contamination risk.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patent changes fermentation parameters including temperature (30-37°C), pH (4.5-5.5), and nutrient composition to maximize nisin production within a shorter time frame. These optimized parameters enable high nisin concentration to be achieved faster, reducing the window for contamination.

Inventive Principle:
Principle #35Parameter changes

3Productivity

If fermentation medium requirements are increased to improve nisin production, then manufacturing costs increase

Engineering Contradiction:
Improvenisin production efficiencyVSAvoidmanufacturing cost
Core Design Contradiction:
ProductivityVSEase of manufacture

Solution Approach 1:

The patent optimizes medium composition parameters by using a defined medium containing glucose (20-50 g/l), peptone (5-20 g/l), and yeast extract (5-20 g/l). This optimized composition achieves high nisin production efficiency while controlling manufacturing costs through precise ingredient specification and cost-effective sources.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses a standardized, defined medium formulation that can be consistently replicated across different production batches. This copying of optimal medium composition ensures reliable nisin production while controlling costs through predictable ingredient requirements and eliminating the need for expensive, complex medium formulations.

Inventive Principle:
Principle #26Copying

4Adaptability or versatility

If nisin containing ferments are produced at a separate plant from food product production, then formulation stability and ease of use are compromised

Engineering Contradiction:
Improveformulation flexibilityVSAvoidhandling and dosing ease
Core Design Contradiction:
Adaptability or versatilityVSEase of operation

Solution Approach 1:

The patent optimizes the physical and chemical parameters of the ferment product by controlling pH (4.5-5.5), viscosity, and concentration to create a stable liquid or semi-liquid formulation. These parameter changes enable the ferment to be easily handled, stored, and dosed in food production, improving ease of operation while maintaining versatility.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a formulated product with specific local properties (liquid or semi-liquid consistency, stable pH, controlled viscosity) that are optimized for ease of handling and dosing. This localized optimization of product properties makes the ferment suitable for direct incorporation into food products while maintaining its nisin activity and preservative function.

Inventive Principle:
Principle #3Local quality

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 process results in a physically stable, high-nisin content liquid product that is easy to handle and store, reducing manufacturing costs while maintaining nisin activity and meeting regulatory standards.

Implementation Method 1

Lactic acid fermentation results in inhibition of the growth of other contaminating bacteria. Due to the pH reduction of the systems with lactic acid produced via lactic acid fermentation, decay and quality deterioration of such food products can be prevented and/or reduced.

Methodology Applied
Scientific EffectLactic acid fermentation: Fermentation

Implementation Method 2

the pH of the fermentation broth is controlled by addition of an alkalization agent comprising an alkaline potassium salt

Methodology Applied
Scientific EffectNeutralization: Chemical Bonding

Implementation Method 3

it has been determined that certain additional antimicrobial substances, such as bacteriocins, are produced by some lactic acid bacteria. A known bacteriocin for the control of pathogens in food is nisin. Nisin is produced by Lactococcus lactis strains and inhibits a broad range of Gram-positive bacteria.

Methodology Applied
Scientific EffectBacteriocin production: Fermentation

Data Source

PatentUS10040833B2Nisin production process
Publication Date: 2018.08.07 PURAC BIOCHEM BV
  • US10040833B2 patent drawing
  • US10040833B2 patent drawing

AI summary

The present invention relates to fermentation processes. The objective of the invention was to provide methods for producing nisin containing ferments and formulating such ferments into preservatives. It was in particular an object of the present invention to provide improved processes for producing nisin containing ferments by simple and efficient (batch) culturing and allowing for simple down-stream processing either into a liquid, semi-liquid or a dry powder product, having sufficient nisin content and stability, good handling properties and satisfactory organoleptic properties. Such processes are provided, as well as the products that can be obtained with it and their use.