Computational Enzymology and Organophosphorus Degrading Enzymes: Promising Approaches Toward Remediation Technologies of Warfare Agents and Pesticides

Abstract

The re-emergence of chemical weapons as a global threat in hands of terrorist groups, together with an increasing number of pesticides intoxications and environmental contaminations worldwide, has called the attention of the scientific community for the need of improvement in the technologies for detoxification of organophosphorus (OP) compounds. A compelling strategy is the use of bioremediation by enzymes that are able to hydrolyze these molecules to harmless chemical species. Several enzymes have been studied and engineered for this purpose. However, their mechanisms of action are not well understood. Theoretical investigations may help elucidate important aspects of these mechanisms and help in the development of more efficient bio-remediators. In this review, we point out the major contributions of computational methodologies applied to enzyme based detoxification of OPs. Furthermore, we highlight the use of PTE, PON, DFP, and BuChE as enzymes used in OP detoxification process and how computational tools such as molecular docking, molecular dynamics simulations and combined quantum mechanical/molecular mechanics have and will continue to contribute to this very important area of research.

Steady-State Kinetics of Enzyme-Catalyzed Hydrolysis of Echothiophate, a P–S Bonded Organophosphorus as Monitored by Spectrofluorimetry

“…OP hydrolases are of great biotechnological and medical interest. Phosphotriesterases (PTE) of various origins, in particular, can be used for detection of OPs [13], decontamination and remediation [8,[14][15][16][17][18] and for therapy of OP poisoning as catalytic bioscavengers [7,[19][20][21][22]. Because OPs are hemi-substrates of ChEs, research of novel human ChE mutants capable of hydrolyzing OPs is of great interest for improving catalytic bioscavenger-based medical countermeasures of OP poisoning [23][24][25] and implementation of pseudocatalytic bioscavenger systems composed of ChE-reactivator [26][27][28].…”

Biodegradation of Organophosphorus Compounds Predicted by Enzymatic Process Using Molecular Modelling and Observed in Soil Samples Through Analytical Techniques and Microbiological Analysis: A Comparison

“…For this reason, OPs are intensively used in tropical regions to prevent the transmission of illnesses such as dengue, Zika, yellow fever, and chikungunya [7,8]. However, it is estimated that only 5% of this kind of compound reaches the targeted organisms [9], and the remainder may cause significant changes in ecological parameters.…”

“…The microbial cells, with the action of some enzymes, present detoxification activities for bioremediation purposes. If a nerve agent has been used, OP-degradation enzymes have the potential to promote a fast hydrolysis compared to traditional chemical methods, with less impact to the environment [9].…”

“…These enzymes were further broken down into two subgroups -the aryldialkylphosphatases (EC 3.1.8.1) (also referred to as organophosphorus hydrolases and PTEs) that prefer substrates bearing P-O or, alternatively, P-S bonds; and the diisopropyl-fluorophosphatases (EC 3.1.8.2) (also including organophosphorus acid anhydrolase (OPAA)), which are more active against OP compounds with P-F or P-CN bonds [21]. PTE is encoded by the organophosphorus-degrading (opd) gene and this is part of the amidohydrolase superfamily [9,21]. All PTEs are metal-dependent hydrolases, that is, there is a requirement for a divalent metal, which directly binds to the substrate to favor the catalysis process [23].…”

“…It can be affirmed that biodegradation of OPs is an important process to protect living beings and the environment of the hazardous effects of this compound. As the hydrolysis is the principal process involved, the degradation will be better comprehended through the study of the behavior of hydrolytic enzymes in the media [9]. It is known that there are different ways of estimating biodegradation, with most of them being structure-based methods [27].…”