Disclosed is a mutated lactonase belonging to the phosphotriesterase-like lactonase family, which increases the susceptibility of bacteria to antimicrobial agents as compared to the use of antimicrobial agents alone.

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).

Mutated hyperthermophilic PTE having a lactonase activity derived from a hyperthermophilic phosphotriesterase corresponding to the consensus sequence of SEQ ID NO: 1, the mutated PTE including the at least one mutation chosen amongst 53 putative positions and the mutated PTE having enhanced properties. Also provided are compositions including the mutated hyperthermophilic PTE and the uses thereof, notably as bioscavenger of organophosphate compounds or as quorum quencher of the bacteria using lactones to communicate.

Mutated hyperthermophilic PTE having a lactonase activity derived from a hyperthermophilic phosphotriesterase corresponding to the consensus sequence of SEQ ID NO: 1, the mutated PTE including the at least one mutation chosen amongst 53 putative positions and the mutated PTE having enhanced properties. Also provided are compositions including the mutated hyperthermophilic PTE and the uses thereof, notably as bioscavenger of organophosphate compounds or as quorum quencher of the bacteria using lactones to communicate.

The instant invention provides methods and related compositions for identifying polypeptides with improved stability and/or enzymatic activity in comparison to native forms, wherein the identified polypeptides comprise one or more non-natural amino acids. In certain embodiments, the present invention relates to novel phosphotriesterase enzymes comprising one or more non-natural amino acids. In a particular embodiment, the instant invention provides novel phosphotriesterase enzymes with greater stability and/or enhanced activity in comparison to native forms of the enzyme. The present invention also relates to compositions comprising novel phophotriesterase enzymes, such as prophylactics, decontaminants, animal feedstocks, and assay kits.