Case ID: M19-049L

Published: 2020-01-22 07:59:05

Last Updated: 1665079374


Tsafrir S Leket-Mor
Katherine Larrimore
Ismail (John) Kazan
Sefika Ozkan
Janet Neisewander

Technology categories

Life Science (All LS Techs)PharmaceuticalsProtein/Pharma Production in Plants

Technology keywords


Licensing Contacts

Jovan Heusser
Director of BD LS
[email protected]

Plant-Expressed Butyrylcholinesterase Mutants

Butyrylcholinesterase (BChE) is a versatile enzyme, capable of binding or hydrolyzing many natural and man-made toxicants of the central and peripheral nervous system. BChE is also able to detoxify psychoactive plant alkaloids such as cocaine into non-psychoactive metabolites. While the catalytic activity of WT hBChE against cocaine is measurable, it is slow, limiting its utility in treating drug overdose and addiction. Further, current expression systems for producing cocaine hydrolase variants of BChE are difficult and expensive to scale up.


Researchers at Arizona State University have developed novel BChE mutants that are highly efficient recombinant cocaine hydrolases. A greater than 2000-fold improvement in catalytic efficiency is seen in the mutants compared to the wild type plant-derived enzyme. Because these mutants are capable of binding and/or hydrolyzing a diverse array of compounds, they are also useful in detoxification of organophosphorus nerve agents as well as acetylcholine receptor antagonists. Further, acetylcholine, a crucially important substrate, is not significantly hydrolyze by these mutants. Plant based expression systems add to the utility of these mutants such that clinically relevant quantities can be produced and scaled easily and inexpensively.


These BChE mutants represent new therapies for cocaine-related pathologies in addition to their utility as bioscavengers against other harmful agents making them practical and useful multivalent therapeutic candidates. 


Potential Applications

•       Detoxifying organophosphate nerve agents (e.g. paraoxon) and pesticides

•       Detoxifying psychoactive plant alkaloids such as cocaine to treat overdose or addiction

•       Binding to and counteracting the toxicity of various anticholinesterases


Benefits and Advantages

•       Increased and faster catalytic efficiency of cocaine hydrolysis

•       Generates non-psychoactive metabolites

•       No significant increase in hydrolysis of acetycholine

•       Plant based expression system reduces production costs and eases scalability

•       One variant hydrolyzes cocaine close to the upper limit set by substrate diffusion rates

•       >2000-fold improved catalytic efficiency compared to the wild type plant-derived enzyme

•       each of the variants were 40–50 fold more sensitive to both OPs paraoxon and Iso-OMPA than the wild type enzyme


For more information about this opportunity, please see

Larrimore et al – Scientific Reports – 2017

For more information about the inventor(s) and their research, please see

Dr. Mor’s departmental webpage

Dr. Ozkan’s departmental webpage