Mutated Organophosphorus Acid Anhydrolase for Sarin Degradation
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Solution Overview
Problem
Current organophosphorus acid anhydrolases have limited catalytic activity against the highly toxic nerve agent Sarin, making them impractical for decontamination or medical countermeasures.
Innovation Solution
A non-wild-type organophosphorus acid anhydrolase protein with mutations at positions 212 and 342, specifically substituting Tyrosine with Phenylalanine and Valine with Isoleucine, respectively, is developed to enhance catalytic efficiency against Sarin.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If wild-type organophosphorus acid anhydrolase is used, then the enzyme can degrade various organophosphorus compounds, but its catalytic activity against Sarin is marginal and not practically useful
Solution Approach 1:
The patent applies parameter changes by modifying specific amino acid residues in the enzyme sequence. Two specific mutations are introduced: Y212F (Tyrosine to Phenylalanine at position 212) and V342I (Valine to Isoleucine at position 342). These parameter changes in the enzyme's primary structure alter its catalytic properties, resulting in at least eight times greater catalytic efficiency against Sarin compared to the wild-type enzyme.
2Productivity
If the enzyme structure is modified to improve Sarin degradation, then catalytic efficiency increases, but the enzyme sequence becomes non-wild-type requiring engineering
Solution Approach 1:
The patent applies local quality by making targeted, localized modifications to specific positions in the enzyme sequence rather than globally altering the entire protein structure. Only two specific amino acid positions (212 and 342) are modified with precise substitutions (Y212F and V342I), while the rest of the enzyme structure remains unchanged. This localized approach achieves enhanced Sarin degradation while maintaining overall enzyme integrity and simplicity.
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 mutated enzyme demonstrates at least eight times greater catalytic efficiency against Sarin compared to the wild-type enzyme, making it suitable for in vivo treatment and decontamination of Sarin from surfaces and environments.
Implementation Method 1
a non-wild type organophosphorus acid anhydrolase protein ("OPAA") that includes a mutation at each of sequence positions 212, and 342 of SEQ ID NO: 1
Implementation Method 2
organophosphorus acid ("OPA") anhydrolases ("OPAA") (EC 3.1.8.2) can catalyze the hydrolysis of a variety of OP compounds
Data Source
AI summary
Disclosed herein are non-wild-type organophosphorus acid anhydrolases having two site mutations, methods of production, and methods of use to effectively degrade toxic chemicals such as ((RS)-Propan-2-yl methylphosphonofluoridate) (Sarin) and other organophosphorus compounds.