Development catalytic bioscavengers for detoxification from herbicides
Herbicides claim most of its poison victims among farm workers and farmers who are not protected when they spray the herbicide. Severe cases of poisoning are difficult to treat and there is a high mortality. There is no direct antidote for most herbicide poisoning. These problems stimulate the development of enzyme bioscavengers to detoxify highly toxic herbicides. Bioscavengers are biomolecules that specifically react and detoxify toxic compounds. Thus, enzymes reacting with poisonous compounds can be used as bioscavengers for neutralization of toxic molecules before they reach physiological targets [1,2]. Enzyme bioscavengers can be used for application on skin, mucosa and wounds as active components of topical skin protectants and decontamination solutions.
The successful creation of efficient enzyme bioscavengers has been reported. For example, mutants of human butyrylcholinesterase have been made that hydrolyze cocaine at a high rate . Trovaslet-Leroy et al., have reported the design of mutants of human cholinesterases capable of hydrolyzing organophosphorus compounds . Other enzymes and proteins from blood and organs, and secondary biological targets of organophosphorus compounds and carbamates are potential bioscavengers [1,2].
Currently, herbicides generally are decontaminated using reactive chemistry-based decontaminants that are either bleach-based or strong oxidants . These agents, some toxic themselves, can generate toxic by-products, adversely affecting the environment and are harming the user. Thus, they are particularly difficult to use on humans. Thus, a critical need remains for other cutting-edge technologies that can quickly and effectively mitigate the consequences of toxic pesticides. Enzyme catalysis offers numerous advantages over traditional chemical decontamination solutions by being non-toxic, non-corrosive, non-flammable, easy to use, and environmentally friendly [4,5].There are several general requirements for the use of enzyme-degrading herbicides as medical countermeasures against berbicide poisoning. Enzymes must have a wide spectra of activity, and ideally, enantioselectivity for toxic stereoisomers. Their mass production under GMP conditions must be realizable at a reasonable cost. Long-term storage without activity loss must be possible under field conditions. These requirements are fulfilled by GSTs, and stimulated the focus of the present proposal on the development of engineered GST variants with enhanced catalytic activity towards herbicides. The catalytic activity of native GSTs towards pesticides is comparable low and therefore protein engineering efforts is considered necessary for increasing their activity. GSTs are very adaptable platform for engineering new or improved catalytic activities, particularly with respect to the detoxification of synthetic compounds.
1. Trovaslet-Leroy M, Musilova L, Renault F, Brazzolotto X, Misik J, Novotny L, Froment MT, Gillon E, Loiodice M, Verdier L, Masson P, Rochu D, Jun D, Nachon F. Organophosphate hydrolases as catalytic bioscavengers of organophosphorus nerve agents. Toxicol Lett. 2011 Sep 25;206(1):14-23. Epub 2011 Jun 12.
2. diTargiani RC, Chandrasekaran L, Belinskaya T, Saxena A. In search of a catalytic bioscavenger for the prophylaxis of nerve agent toxicity. Chem Biol Interact. 2010 Sep 6;187(1-3):349-54. Epub 2010 Feb 20.
3. Bencharit S, Morton CL, Xue Y, Potter PM, Redinbo MR. Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme. Nat Struct Biol. 2003 May;10(5):349-56.
4. Rylott EL, Lorenz A, Bruce NC. Biodegradation and biotransformation of explosives. Curr Opin Biotechnol. 2010 Nov 18, (in press).
5. Raynes JK, Pearce FG, Meade SJ, Gerrard JA. Immobilization of organophosphate hydrolase on an amyloid fibril nanoscaffold: Towards bioremediation and chemical detoxification. Biotechnol Prog. 2010 (in press).