Bacillus Fermentation with Defined Medium and Magnesium Feed
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Solution Overview
Problem
Current industrial fermentation processes for producing proteins using Bacillus species require complex media due to regulatory effects, leading to lower productivity and higher costs with chemically defined media being deemed unsuitable for industrial-scale protein production.
Innovation Solution
A chemically defined fermentation medium is used with Bacillus cells inoculated under an inducer-independent promoter, supplemented with chemically defined carbon sources and magnesium ions, exceeding 200 g of carbon source per liter and 0.1 g of magnesium ions per liter, to support growth and protein expression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If complex media are used for industrial fermentation of Bacillus cells, then productivity and protein yields are improved, but manufacturing costs increase and process consistency deteriorates
Solution Approach 1:
The patent applies parameter changes by precisely controlling the concentrations of individual chemically defined components in the medium, particularly maintaining a specific ratio of carbon to nitrogen sources and adjusting pH and temperature parameters to optimize protein production in chemically defined media, thereby achieving high productivity without using complex media
2Productivity
If complex media are used for industrial fermentation of Bacillus cells, then protein yields are improved, but process consistency and quality control deteriorate
Solution Approach 1:
The patent uses parameter changes by precisely controlling the concentrations of individual chemically defined components, particularly maintaining specific ratios of carbon to nitrogen sources and optimizing pH and temperature parameters, thereby achieving both high protein yields and consistent process quality
Solution Approach 2:
The patent implements feedback control by monitoring key process parameters such as pH, dissolved oxygen, and nutrient consumption rates, and adjusting feeding rates and aeration accordingly to maintain optimal conditions for protein production, ensuring both high yields and process consistency
3Stability of the object's composition
If chemically defined media are used for industrial fermentation, then process consistency and analysis capabilities are improved, but productivity and protein yields deteriorate
Solution Approach 1:
The patent applies parameter changes by precisely controlling the concentrations of individual chemically defined components, particularly maintaining a specific ratio of carbon to nitrogen sources and adjusting pH and temperature parameters to optimize protein production, thereby achieving both process consistency and high protein yields in chemically defined media
Solution Approach 2:
The patent implements dynamic feeding strategies where the addition rates of carbon and nitrogen sources are continuously adjusted based on cell growth phase and nutrient consumption rates, allowing the system to adapt to changing metabolic requirements and achieve high productivity while maintaining process consistency
4Adaptability or versatility
If complex media are used for industrial fermentation, then nutrient availability is improved, but downstream processing complexity and costs increase
Solution Approach 1:
The patent extracts and individually controls the essential nutrient components (carbon sources, nitrogen sources, minerals, vitamins) that were previously provided as complex mixtures, allowing precise formulation of chemically defined media that meets all nutritional requirements while eliminating the need for complex downstream processing to remove contaminants from complex media
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 enables industrially relevant protein yields and titers, overcoming the limitations of complex media while maintaining the advantages of chemically defined media, such as improved consistency and analysis capabilities.
Implementation Method 1
The biotechnological production of these useful substances is conducted via fermentation and subsequent purification of the product
Data Source
AI summary
The present invention is directed to an industrial fermentation process for cultivating a Bacillus cell in a chemically defined fermentation medium and a method for producing a protein of inter-est comprising the steps of providing a chemically defined fermentation medium, inoculating the fermentation medium with a Bacillus cell comprising a gene encoding a protein of interest, cultivating the Bacillus cell in the fermentation medium under conditions conductive for the growth of the Bacillus cell and the expression of the protein of interest, wherein the cultivation of the Bacillus cell comprises the addition of one or more feed solutions comprising one or more chemically defined carbon sources and magnesium ions to the fermentation medium.