Enzymatic detoxification: a sustainable means of degrading toxic organophosphate pesticides and chemical warfare nerve agents

Abstract

Organophosphorus (OP) compounds are highly toxic molecules mainly used as pesticides. OP compounds also include nerve gases used in the past as chemical warfare agents and collectively OP pesticides and nerve gases are referred to as nerve agents (NA). An intensive, widespread use of pesticides since the 20th century has resulted in the emergence of an urgent global issue concerning both environment and human health. In addition, past terroristic acts and the recent dramatic events in Syria highlighted more than ever the need to explore applicable strategies for the sensing, decontamination and detoxification of these compounds in stored bulks, on critical surfaces and media (food, water and air) and for in vivo prophylaxes and therapies.OP compounds, act as covalent inhibitors of acetylcholinesterase (AChE) in the nerve system of vertebrates, thus posing a substantial threat to the ecosystem. In order to address a strong demand for the establishment of an environmental monitoring system and remediation process for NA, an increasing number of studies have been focused on the enzymatic degradation in vitro. Use of enzymes for detoxification and decontamination of toxic NA could provide a long‐term benefit as it is environmentally friendly compared with conventional methods such as chemical treatments and incineration. This review presents an overview of the current state of enzymatic detoxification research against NA. This includes the detailed characterization and protein engineering for the improvement in NA‐degrading activities of such enzymes. Research on biosensors for NA detection and identification, although important in the field, has not been treated in this review. Instead special attention has been paid to the Phosphotriesterase‐Like‐Lactonase (PLL) enzyme family. Several PLL enzymes have been isolated from hyperthermophilic Archaea or thermophilic/extremophilic Bacteria, and exhibit exceptional thermal stability. Extremophilic PLLs therefore hold promise for potential industrial application towards NA detoxification. © 2018 Society of Chemical Industry

Microbial Phosphotriesterase: Structure, Function, and Biotechnological Applications

“…In this case, the metal ion in Pseudomonas diminuta and Sphingobium fuliginis strain ATCC 27551 PTE have Zn 2+, as the ion, whereas for the Geobacillus stearothermophilus PTE it is Co 2+ [7,30]. In the absence of a substrate, the α zinc metal was reported as buried near to His55, His 57, and Asp 301, and the β zinc metal was more exposed to the solvent [6,7,30]. The divalent metal ions in the active site center are reported to contribute to the activity and stability of the enzyme.…”

“…The active site pocket of the PTE in a hydrophobic condition contains two metal ions (Zn 2+ Mn 2+ , Co 2+ , and Cd 2+ ) bridged with side-chains of histidine residues that are clustered around the metal atoms [22,27]. A number of the crystal structures of PTE isolated from bacteria such as Pseudomonas pseudoalcaligenes (2.1 Å), Pseudomonas diminuta (2.0 Å), Mycobacterium tuberculosis (2.27 Å), Agrobacterium radiobacter (1.99 Å), Geobacillus stearothermophilus (2.09 Å), and Geobacillus kaustophilus HTA426 (2.05 Å) have been determined [4,7,16,28,29]. In this review, three crystal structures of PTEs from Pseudomonas diminuta, Sphingobium fuliginis strain ATCC 27551, and Geobacillus stearothermophilus (PLL) are used as examples in this section to shown the similarities and differences in their 3D structure Figure 2.…”

“…In addition, all PTEs require divalent metals to directly ligate the substrate to simplify the hydrolysis process Figure 2(B1-B3) [5,6]. In this case, the metal ion in Pseudomonas diminuta and Sphingobium fuliginis strain ATCC 27551 PTE have Zn 2+, as the ion, whereas for the Geobacillus stearothermophilus PTE it is Co 2+ [7,30]. In the absence of a substrate, the α zinc metal was reported as buried near to His55, His 57, and Asp 301, and the β zinc metal was more exposed to the solvent [6,7,30].…”

“…Similarly, in thiophosphotriesters (methyl parathion) and phosphorothiolesters (malathion), the phosphate group is still in the center but the phosphoryl oxygen is replaced by sulfur and one or more of the ester oxygens are replaced by sulfur Figure 1B,C. To date these compounds are still widely used especially in agricultural industries [7]. Moreover, OPs compounds are easily drained into ground water that in turn will pollute water supplies and surrounding land areas [8].…”

“…Many alternative technologies have been studied and developed to resolve this problem, using various chemical, physical, and biological methods. Unfortunately, most of these methods are expensive and may not suitable or even safe for the decontamination of human beings [7]. They may be very harsh and may not be very specific [3].…”