Enzymatic Route To Insect Repellents From Bio-based Feedstocks

Insect-vectored disease is a major global health challenge, and its incidence will increase in temperate zones as vector species expand out of the tropics with climate change. Biting insects are responsible for the transmission of diseases including malaria, dengue, leishmaniasis, lyme disease, encephalitis, etc causing many hundreds of thousands of deaths per year. Protection against insect bites is a crucial method for preventing these diseases. The only defence against insect bites for an individual in the outdoors (apart from complete clothing coverage) is to use a skin-applied insect repellent product. The most well-known insect repellent in these products is DEET (N,N-Diethyl-meta-toluamide), a synthetic chemical ultimately derived from fossil fuels. However, a significant proportion of consumers choose to not use existing, effective, insect repellent products out of an aversion to applying synthetic chemicals to their (or their children's) skin. These consumers will either not use a repellent at all or use ineffective products advertised as 'natural'. The consequence is an avoidable increase in disease incidence impacting the individual and society. Dihydronepetalactone (DHN) is a new insect repellent which has similar repellent properties to DEET but other superior properties including pleasant smell and lack of sensitisation activity. This compound is derived from the essential oil of the catmint plant so has the natural product cachet desired by a large segment of consumers. Unlike other products with natural credentials, it combines the efficacy of synthetics with the safety of a natural product. Entomol Products LLC have brought a DHN based product to the US market. Although starting with a plant-derived feedstock, the current production of DHN involves a precious-metal-catalysed hydrogenation step, requiring solvent together with high pressure and temperature reaction conditions. It would be highly beneficial to replace this step with a biocatalytic process, eliminating the need for metal catalyst, natural gas-derived hydrogen, and solvent, reducing energy requirements, for enhanced sustainability and natural credentials. The University of York have recently demonstrated proof-of-principle that the active molecule in the repellent product, DHN, can be generated from the same feedstock - unrefined catmint essential oil - using enzymatic catalysis. The funding here will allow us to move this research from proof of principle to practical demonstration of biocatalytic DHN production. The project will involve (1) optimisation of biocatalysis reaction conditions, (2) optimisation of enzyme catalysts, (3) investigation into alternative routes to DHN formation and (4) development of the business case. The University of York will be working with Entomol Products LLC as a project partner, who are providing material, information into the commercial production of DHN and a possible route to market. The aim of this project is to develop a sustainable, bio-based route to a fully natural insect repellent. This product from this route will be attractive to consumers, encouraging greater use of insect repellents and therefore improving global health outcomes with respect to insect-vectored disease.