Every year the loss of valuable livestock to invertebrate parasites, both endoparasites (nematodes or helminths) and ectoparasites (flies, ticks, mites and sea lice) totals >£34 billion globally. This is despite the fact that farmers spend ~£4.5 billion globally on parasiticides (compounds to treat parasitic infections). New products are continually needed as new parasites emerge and existing parasites evolve resistance. To compound this issue fewer novel agents are entering the market due to the increasing difficulties of discovering novel compounds and getting regulatory approval. In this project, Acidophil collaborating with Isomerase aim to combine synthetic biology and chemistry to generate novel natural product derived parasiticides to address the pressing unmet need in food animal health for new and cost effective parasiticides

Some plants, fungi and bacteria produce chemicals (natural products or NPs) with potent bioactivity as part of their chemical ecology. These NPs have excellent activity against human diseases, crop- and animal- pests. However, they are complex molecules, naturally made in small quantities, so they can be challenging and expensive to produce, significantly limiting their market potential. Currently, they are produced through a combination of fermentation to make a NP which is then modified into the final product via one or more chemical steps. By starting from what nature provides, only very restricted chemistries are accessible, which can make the manufacturing process more complex, hazardous and expensive. Acidophil and it’s strategic partner, Isomerase are developing an innovative process of manufacturing NP medicines, starting with rationally designed products made by genetically engineered microbes (“unnatural” NPs) that are carefully designed to enable facile, safe and inexpensive chemistries. As proof-of-concept of this innovative technology, we are applying this approach to a particular NP parasiticide currently used in pets, to dramatically reduce the cost of manufacturing of this valuable animal medicine and make it affordable to farmers for use in food animals. Once proven, this manufacturing innovation will revolutionize biotechnology and enable us to produce lower cost NPs, which can then be developed into excellent human pharmaceuticals, crop protection- and animal health- products.

Confirmation of scaleability of new tools for accessing novel natural products with use in human and animal health and as agrochemicals.

Development of new tools for rational biological synthesis of novel natural products with potential use in design of improved anti-infectives, anticancer agents, agrochemicals and immune modulating agents.

Generation and analysis of a library of novel Natural Products using a new recombineering technology, with potential for use in pharmaceutical development, as treatments in indications such as infectious diseases, oncology and inflammation, as agrochemicals and fine chemicals.

Worldwide, £100s of billions of crops and livestock are lost annually to pests and disease. Population growth and global improvements in standards of living mean that even more productivity must be gained from limited arable land. Unfortunately, some existing crop and livestock protection agents are losing effectiveness due to pest resistance and fewer novel agents are entering the market. Macrocyclic lactone compounds represent over a £1 billion annual market share, but existing products have significant shortcomings. Acidophil’s innovation, to be evaluated in this early stage feasibility study, consists of combining synthetic biology and chemistry to generate novel and improved versions of these compounds addressing the shortcomings of existing products.