Microbial Diamine Oxidase for Histamine Degradation at Acidic pH
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Solution Overview
Problem
Current methods for degrading biogenic amines like histamine and tyramine in food and human bodies are inefficient, with commercially available porcine DAO being limited by substrate inhibition, stability issues, and inability to operate at acidic pH and low temperatures, making industrial applications economically unviable and unsuitable for histamine-tolerant individuals.
Innovation Solution
A diamine oxidase (DAO) enzyme derived from Glutamicibacter halophytocola (DAO-GH) with specific amino acid sequences or high sequence identity, exhibiting high activity at acidic pH and low temperatures, capable of efficiently degrading histamine and tyramine in food products and human bodies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If porcine DAO is used to degrade histamine in food and human bodies, then histamine degradation activity is provided, but the enzyme suffers from substrate inhibition at histamine concentrations greater than 56 mg/L, limited stability with half-life of approximately 19 minutes in simulated intestinal fluid, and inability to operate at acidic pH and low temperatures
Solution Approach 1:
The patent applies parameter changes by modifying the operational conditions of the DAO enzyme. Specifically, the enzyme is engineered or selected to function optimally at acidic pH values (pH 2-6) and low temperatures (4-25°C), which are the actual conditions found in fermented foods and the human gastrointestinal tract. This resolves the contradiction by changing the physical-chemical parameters of enzyme operation to match the target environment, thereby improving both reliability and adaptability simultaneously.
2Productivity
If DAO is used directly in foods or during fermentation to produce histamine-free foods, then histamine degradation is achieved, but the commercially available DAO from pig kidneys cannot be provided in sufficient quantities for economically viable industrial application
Solution Approach 1:
The patent employs the principle of using a readily available, cost-effective enzyme source that can be produced in large quantities. By utilizing DAO from microorganisms or plant sources instead of porcine kidney, the invention enables scalable production of sufficient enzyme quantities for industrial food processing applications, resolving the contradiction between productivity and enzyme availability.
3Reliability
If porcine DAO is administered in dietary supplements to support human endogenous DAO, then histamine metabolism is intended to be enhanced, but the activity required for satisfactory histamine reduction is considerably larger than expected and the enzyme cannot be extracted and administered in sufficient quantities
Solution Approach 1:
The patent resolves this contradiction by changing the operational parameters of the DAO enzyme to be stable and active under gastrointestinal conditions (acidic pH, low temperature). This enables the enzyme to withstand stomach acid and remain functional until it reaches the intestine, allowing effective dosages to be achieved without requiring excessive enzyme quantities that would be needed with porcine DAO.
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
DAO-GH provides robust degradation of histamine and tyramine in food products and human bodies, offering a viable industrial solution and effective treatment for histamine intolerance, with high stability and activity in relevant pH and temperature ranges.
Implementation Method 1
This enzyme degrades histamine by oxidative deamination, resulting in the reaction products (imidazol-4-yl)acetaldehyde, hydrogen peroxide and ammonia
Data Source
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AI summary
The present invention relates to functional foods and dietary supplements comprising a specific diamine oxidase (DAO) enzyme derived from Glutamicibacter halophytocola, uses of said enzyme and respective methods for the production of biogenic amine-depleted products, uses of said enzyme as a biosensor for the analysis of one or more biogenic amine(s), as well as said enzyme for use in medicine, in particular for use in the prevention or treatment of a condition or disease that is associated with increased levels of biogenic amines.