Antimicrobial Peptide Variants for Neutral-pH and Heat Stability
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Solution Overview
Problem
Existing antimicrobial peptides like nisin A are unstable in neutral and alkaline ranges and not highly thermostable, limiting their application and effectiveness against gram-negative bacteria and fungi.
Innovation Solution
Development of polypeptides with 85% to 100% sequence identity to specific amino acid sequences (SEQ ID NO: 1 to 6) or modified versions, produced through chemical synthesis, in-vitro translation, or bacterial culture, exhibiting high stability in neutral and alkaline ranges and thermostability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If nisin A is used as a food preservative, then it exhibits high antimicrobial activity against gram-positive bacteria and is stable against acid, but it is unstable within the neutral range and the alkaline range and not highly thermostable
Solution Approach 1:
The invention modifies the amino acid sequence parameters of nisin A to create variants (nisins B and C) with improved pH stability and thermostability while maintaining antimicrobial activity. Specific amino acid substitutions were made to enhance stability in neutral and alkaline ranges without sacrificing the core antimicrobial function.
Solution Approach 2:
The invention creates composite antimicrobial peptides by combining modified nisin sequences with other peptide structures to produce variants that exhibit both the acid stability of nisin A and enhanced stability in neutral/alkaline conditions, effectively creating a composite functional structure.
2Reliability
If nisin A contains abnormal amino acids resulting from post-translational modification, then it achieves its antimicrobial function, but it becomes difficult to synthesize chemically or by recombinant DNA techniques
Solution Approach 1:
The invention creates simplified copy versions of nisin A that replicate its antimicrobial function using standard amino acids without requiring post-translational modification. These copy peptides can be directly synthesized by chemical methods or recombinant DNA techniques, bypassing the complexity of producing abnormal amino acids.
Solution Approach 2:
The invention replaces the complex, difficult-to-synthesize nisin A with simpler peptide variants that can be produced more easily and economically through chemical synthesis or recombinant expression, effectively using simpler structures to achieve the same functional purpose.
3Reliability
If nisin A is used for food preservation, then it is effective against gram-positive bacteria, but it is not effective against gram-negative bacteria and fungi
Solution Approach 1:
The invention modifies nisin A to create variants with expanded functionality that can effectively target multiple types of microorganisms including gram-positive bacteria, gram-negative bacteria, and fungi. The peptide structure was optimized to achieve broad-spectrum antimicrobial activity while maintaining its original acid stability and other beneficial properties.
Data Source
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AI summary
Provided is a polypeptide with antimicrobial activity comprising an amino acid sequence with a sequence identity of 85% to 100% to an amino acid sequence as set forth in any one of SEQ ID NO: 1 to SEQ ID NO: 6 or an amino acid sequence as set forth in any one of SEQ ID NO: 1 to SEQ ID NO: 6 with deletion, substitution, insertion, and/or addition of one or several amino acid residues.