An OPAA enzyme mutant with increased catalytic efficiency on the nerve agents sarin, soman, and GP

Bae, Sue Y; Myslinski, James M.; McMahon, Leslie R.; Height, J.J.; Bigley, Andrew N.; Raushel, Frank M.; Harvey, Steven P.

doi:10.1016/j.enzmictec.2017.11.001

Cited by 21 publications

(15 citation statements)

References 16 publications

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“…Bae et al . showed that a series of mutations in OPAA led to significant increase in activity toward sarin and soman (Bae et al, 2018). Additionally, in these studies, the authors were able to isolate a double mutant version of OPAA that was able to show enantioselectivity for one enantiomer of sarin.…”

Section: Enzymes For Decontaminationmentioning

confidence: 99%

Enzymatic Bioremediation of Organophosphate Compounds—Progress and Remaining Challenges

Thakur

Medintz

Walper

2019

Front. Bioeng. Biotechnol.

101

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Organophosphate compounds are ubiquitously employed as agricultural pesticides and maintained as chemical warfare agents by several nations. These compounds are highly toxic, show environmental persistence and accumulation, and contribute to numerous cases of poisoning and death each year. While their use as weapons of mass destruction is rare, these never fully disappear into obscurity as they continue to be tools of fear and control by governments and terrorist organizations. Beyond weaponization, their wide-scale dissemination as agricultural products has led to environmental accumulation and intoxication of soil and water across the globe. Therefore, there is a dire need for rapid and safe agents for environmental bioremediation, personal decontamination, and as therapeutic detoxicants. Organophosphate hydrolyzing enzymes are emerging as appealing targets to satisfy decontamination needs owing to their ability to hydrolyze both pesticides and nerve agents using biologically-derived materials safe for both the environment and the individual. As the release of genetically modified organisms is not widely accepted practice, researchers are exploring alternative strategies of organophosphate bioremediation that focus on cell-free enzyme systems. In this review, we first discuss several of the more prevalent organophosphorus hydrolyzing enzymes along with research and engineering efforts that have led to an enhancement in their activity, substrate tolerance, and stability. In the later half we focus on advances achieved through research focusing on enhancing the catalytic activity and stability of phosphotriesterase, a model organophosphate hydrolase, using various approaches such as nanoparticle display, DNA scaffolding, and outer membrane vesicle encapsulation.

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Section: Enzymes For Decontaminationmentioning

confidence: 99%

Enzymatic Bioremediation of Organophosphate Compounds—Progress and Remaining Challenges

Thakur

Medintz

Walper

2019

Front. Bioeng. Biotechnol.

101

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“…Different degrading enzymes have optimum substrates. Paraoxonase (with Ca 2+ as metal ions activity center) displays a preference for sarin and soman [46], OP acid anhydrolase (with Mn 2+ as metal ions activity center) displays a preference for tabun [47], phosphotriesterase (with Zn 2+ as metal ions activity center) displays a preference for ethyl-substituted OPs and OP-degrading hydrolases (with Co 2+ or Cd 2+ as metal ions activity center) displays a preference for methyl-substituted OPs [25,41]. In present study, OpdB in strain X1 T belongs to OP-degrading hydrolases, which could degrade chlorpyrifos and had high degradation activity against methyl parathion, parathion, profenofos, methidathion and isocarbophos [20].…”

Section: Discussionmentioning

confidence: 99%

Rapid Biodegradation of the Organophosphorus Insecticide Chlorpyrifos by Cupriavidus nantongensis X1T

Shi

Fang

Qin

et al. 2019

IJERPH

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Chlorpyrifos was one of the most widely used organophosphorus insecticides and the neurotoxicity and genotoxicity of chlorpyrifos to mammals, aquatic organisms and other non-target organisms have caused much public concern. Cupriavidus nantongensis X1T, a type of strain of the genus Cupriavidus, is capable of efficiently degrading 200 mg/L of chlorpyrifos within 48 h. This is ~100 fold faster than Enterobacter B-14, a well-studied chlorpyrifos-degrading bacterial strain. Strain X1T can tolerate high concentrations (500 mg/L) of chlorpyrifos over a wide range of temperatures (30–42 °C) and pH values (5–9). RT-qPCR analysis showed that the organophosphorus hydrolase (OpdB) in strain X1T was an inducible enzyme, and the crude enzyme isolated in vitro could still maintain 75% degradation activity. Strain X1T can simultaneously degrade chlorpyrifos and its main hydrolysate 3,5,6-trichloro-2-pyridinol. TCP could be further metabolized through stepwise oxidative dechlorination and further opening of the benzene ring to be completely degraded by the tricarboxylic acid cycle. The results provide a potential means for the remediation of chlorpyrifos- contaminated soil and water.

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“…Since the naturally occurring enzymes have inefficient stereoselectivity/regioselectivity and thermostability, they have not been able to achieve eminence in practical procedures. The emergence of protein engineering techniques such as direct evolution has proven to be a vital tool in engendering various genetic amendments to construct variants of natural enzymes with superior activity compared to their wild types [ 128 , 140 – 143 ].…”

Section: Treatment Strategies For Organophosphorus Poisoningmentioning

confidence: 99%

Organophosphorus Nerve Agents: Types, Toxicity, and Treatments

Mukherjee

Gupta

2020

Journal of Toxicology

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Organophosphorus compounds are extensively used worldwide as pesticides which cause great hazards to human health. Nerve agents, a subcategory of the organophosphorus compounds, have been produced and used during wars, and they have also been used in terrorist activities. These compounds possess physiological threats by interacting and inhibiting acetylcholinesterase enzyme which leads to the cholinergic crisis. After a general introduction, this review elucidates the mechanisms underlying cholinergic and noncholinergic effects of organophosphorus compounds. The conceivable treatment strategies for organophosphate poisoning are different types of bioscavengers which include stoichiometric, catalytic, and pseudocatalytic. The current research on the promising treatments specifically the catalytic bioscavengers including several wild-type organophosphate hydrolases such as paraoxonase and phosphotriesterase, phosphotriesterase-like lactonase, methyl parathion hydrolase, organophosphate acid anhydrolase, diisopropyl fluorophosphatase, human triphosphate nucleotidohydrolase, and senescence marker protein has been widely discussed. Organophosphorus compounds are reported to be the nonphysiological substrate for many mammalian organophosphate hydrolysing enzymes; therefore, the efficiency of these enzymes toward these compounds is inadequate. Hence, studies have been conducted to create mutants with an enhanced rate of hydrolysis and high specificity. Several mutants have been created by applying directed molecular evolution and/or targeted mutagenesis, and catalytic efficiency has been characterized. Generally, organophosphorus compounds are chiral in nature. The development of mutant enzymes for providing superior stereoselective degradation of toxic organophosphorus compounds has also been widely accounted for in this review. Existing enzymes have shown limited efficiency; hence, more effective treatment strategies have also been critically analyzed.

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An OPAA enzyme mutant with increased catalytic efficiency on the nerve agents sarin, soman, and GP

Cited by 21 publications

References 16 publications

Enzymatic Bioremediation of Organophosphate Compounds—Progress and Remaining Challenges

Enzymatic Bioremediation of Organophosphate Compounds—Progress and Remaining Challenges

Rapid Biodegradation of the Organophosphorus Insecticide Chlorpyrifos by Cupriavidus nantongensis X1T

Organophosphorus Nerve Agents: Types, Toxicity, and Treatments

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