US Government As Represented by the Secretary of the Army

University of Georgia Research Foundation, Inc.

Steven P Harvey

Mark A Guelta

Melissa M Dixon

Joseph J DeFrank

Leslie R McMahon

Tu-Chen Cheng

Vipin K Rastogi

Linda L Szafraniec

William T Beaudry

Scott Pegan

Sue Y Bae

Saumil S Shah

The invention comprises isolated, mutant, non-wild-type organophosphorus acid anhydrolase (OPAA) enzymes having two site mutations, methods of production, and methods of use to effectively degrade cylcosarin (GF) (cyclohexyl methylphosphonofluoridate) with greater catalytic efficiency than the wild-type OPAA.

Mutant OPAA enzymes with increased catalytic efficiency on cyclosarin

The invention is directed toward mutant, non-wild-type organophosphorus acid anhydrolases (OPPAs) having three or more site mutations, methods of production, kits and methods of use to effectively degrade toxic V-agent type chemical compounds such as VX, VR, CVX, and VM.

Mutant organophosphorus acid anhydrolase enzymes having increased catalytic efficiency on V-agents

The invention is directed toward mutant, non-wild-type organophosphorus acid anhydrolase enzymes having three site mutations, methods of production, and methods of use to effectively degrade toxic organophosphorus compounds, most preferably GP (2, 2'-dimethylcyclopentyl methylphosphonofluoridate).

Mutant OPAA enzyme with increased catalytic efficiency on GP

The invention is directed toward mutant, non-wild-type organophosphorus acid anhydrolase enzymes having three site mutations, methods of production, and methods of use to effectively degrade toxic organophosphorus compounds, most preferably GP (2,2'-dimethylcyclopentyl methylphosphonofluoridate).

Mutant OPAA enzyme with increased catalytic efficiency on organophosphorus compound GP

Genetically engineered organophosphorus acid anhydrolases (OPAA) with improved catalytic efficiency and relaxed stereospecificity are provided. The variants typically include a mutation at the residue corresponding to H343 of wildtypesp. OPAA. The mutation allows the OPAA enzyme to effectively process both VR enantiomers. The OPAA optionally include one or more mutations selected the residues corresponding to Y212, V342, and I215 of wildtypesp. OPAA which improve the enzyme's catalytic efficiency for VX and VR. A particularly preferred OPAA includes mutations at the residues corresponding Y212F, V342L, I215Y, and H343D relative to wildtypesp. OPAA. Compositions including an effective amount of OPAA to increase hydrolysis of an organophosphate, and methods of use thereof for treating subjects exposed to an organophosphate, or a surface or liquid contaminated with an organophosphate are also provided.

Engineered organophosphorus acid anhydrolases and methods of use thereof

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.

Mutant organophosphorus acid anhydrolases and uses thereof

Disclosed herein are non-wild-type organophosphorus acid anhydrolases having three 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. Also provided are organophosphorus acid anhydrolase mutants capable of degrading Sarin with distinct selective stereospecificity preferences differing from the wild-type organophosphorus acid anhydrolase

Mutant organophosphorus acid anhydrolase enzymes with stereospecificity on Sarin enantiomers and uses thereof

The invention comprises isolated, mutant, non-wild-type organophosphorus acid anhydrolase (OPAA) enzymes having three site mutations, methods of production, and methods of use to effectively degrade organophosphorus compound EA1356 (2-methylcyclohexyl methylphosphonofluoridate) with greater catalytic efficiency than the wild-type OPAA enzyme.

Mutant OPAA enzymes with increased catalytic efficiency on organophosphorus compound EA1356

This invention is directed toward a non-wild-type organophosphorus acid anhydrolase enzyme having two site mutations, method of production, and method of use to more effectively degrade toxic organophosphorus compounds and, in particular, toxic chemical GD (3,3-Dimethylbutan-2-ylmethylphosphonofluoridate), than the wild type organophosphorus acid anhydrolase.

OPAA FL&#x2014;a mutant enzyme with increased catalytic efficiency on organophosphorus compound GD

The invention is directed toward non-wild-type organophosphorus acid anhydrolases having three site mutations, method of production, and method of use to effectively degrade toxic chemical compounds such as (Ethyl({2-[bis(propan-2-yl)amino]ethyl}sulfanyl)(methyl)phosphinate ('VX').

Mutated organophosphorus acid anhydrolases and their uses thereof

The invention is directed toward non-wild-type organophosphorus acid anhydrolases having three site mutations, method of production, and method of use to effectively degrade toxic chemicals such as N,N-diethyl-2-(methyl-(2-methylpropoxy)phosphoryl)sulfanylethanamine) ('VR').

Provided are non-wild-type organophosphorus acid anhydrolases that are capable of degrading (ethyl {2-[bis(propan-2-yl)amino]ethyl}sulfanyl) (methyl)phosphinate and other V-agents. Particular embodiments include an organophosphorus acid anhydrolase including an amino acid substitution at position 212.

Non-wild-type organophosphorus acid anhydrolases for enzymatic decontamination

The present invention is generally related to systems and methods to permit the growth of anaerobic, ethanol-producing bacteria using pretreated biomass such as cellulose in a manner to facilitate the efficient conversion of cellulose to ethanol.

Plug flow reactor process for anaerobic cellulosic ethanol

An assay for screening potential hydrolysis enhancing agents capable of facilitating the hydrolysis of a substantially water insoluble halogenated compound such as mustard gas (HD) in an aqueous reaction mixture is disclosed. The assay includes at least one chamber adapted for receiving and retaining the substantially water insoluble mustard gas compound and a potential hydrolysis agent in an aqueous reaction mixture, and a pH indicating agent adapted to produce a visible color change corresponding to the amount of the substantially water insoluble mustard gas compound hydrolyzed in the aqueous reaction mixture wherein the rate of hydrolysis can be established by measuring the change in the detectable signal over time.

Colorimetric assay for the determination of hydrolysis activity from HD and other halogenated organics

The present invention relates to a near-universal non-corrosive, non-toxic, environmentally safe and user friendly decontaminant capable of detoxifying organophosphorus (OP)-based G-type, V-type neurotoxic chemical warfare, sulfur-mustard, and related OP based hazardous industrial materials in a dry powder form. The decontaminant contains OPH enzyme, OPAA enzyme, DFPase enzyme, dehalogenase enzyme, quaternary ammonium salt, a pH control reagent, a fire-fighting agent, and a foaming agent. The decontaminant is mixed with available water for use.

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Lutherville, MD, United States of America

Steven P Harvey