The evolution of phosphotriesterase for decontamination and detoxification of organophosphorus chemical warfare agents

Publication date: Available online 15 May 2019Source: Chemico-Biological InteractionsAuthor(s): Andrew N. Bigley, Frank M. RaushelAbstractThe organophosphorus chemical warfare agents were initially synthesized in the 1930's and are some of the most toxic compounds ever discovered. The standard means of decontamination are either harsh chemical hydrolysis or high temperature incineration. Given the continued use of chemical warfare agents there are ongoing efforts to develop gentle environmentally friendly means of decontamination and medical counter measures to chemical warfare agent intoxication. Enzymatic decontamination offers the benefits of extreme specificity and mild conditions, allowing their use for both environmental and medical applications. The most promising enzyme for decontamination of the organophosphorus chemical warfare agents is the enzyme phosphotriesterase from Pseudomonas diminuta. However, the catalytic activity of the wild-type enzyme with the chemical warfare agents falls far below that seen with its best substrates, and its stereochemical preference is for the less toxic enantiomer of the chiral phosphorus center found in most chemical warfare agents. Rational design efforts have succeeded in the dramatic improvement of the stereochemical preference of PTE for the more toxic enantiomers. Directed evolution experiments, including site-saturation mutagenesis, targeted error-prone PCR, computational design, and quantitative library analysis, have system...
Source: Chemico Biological Interactions - Category: Biochemistry Source Type: research