Biocleave uses soil bacteria to create synthetic insect pheromones as natural crop defence
Insect pheromones used in nature for communication are to be engineered synthetically to produce powerful crop protection tools, following a collaboration between biotech company Biocleave and Rothamsted Research. Biocleave uses a benign soil bacterium, Clostridium, as a micro-factory to create recombinant proteins such as enzymes, for use in the production of biopesticides.
Semiochemicals, such as pheromones, are naturally occurring compounds used by insects to convey specific messages. Disrupting these communications can prevent them from attracting mates and breeding and so provide an exciting opportunity for the creation of highly specific biopesticides that are non-toxic to beneficial insects and natural predators.
Naturally occurring compounds are difficult to make using the traditional chemistry techniques that are currently used to generate fertilisers and pesticides from petrochemicals. Instead, the single-cell organism, E.coli, is often used as a bio-factory to create these. However, some of the ingredients of semiochemicals are toxic to E.coli, so as production of these novel crop protection compounds increases, an alternative bio-factory is needed.
Biocleave overcomes a bottleneck in production
Biocleave is using a new organism, the soil bacterium Clostridium, to produce biological semiochemicals.
Dr Liz Jenkinson, CEO of Biocleave, explains: “There are a whole host of semiochemicals, including sex pheromones, that have been demonstrated to have efficacy at replacing traditional pesticides.
“However, it is difficult to produce these semiochemicals as they are created through pathways of enzymes – so obtaining these enzymes is currently the bottleneck; preventing the synthetic production of these biopesticides. Essentially we are harnessing the power of nature to make these enzymes. and then supporting various production partners, to use those enzymes to make the final biopesticide.”
Biocleave gained investment in December 2020, which has enabled it to develop its novel gene editing technology CLEAVE™ and rebrand the company to take it to market.
Strong track record
The original company, Green Biologics, was an industrial biotech company using Clostridium to make biochemicals, biobutanol and bioacetone – it had a plant in the US to produce these biomolecules. In parallel with this the company was developing new technologies and one strand has been using Clostridium as a new host for making recombinant proteins.
Recombinant proteins can include drugs, antibodies and enzymes for disease treatment. A small section of DNA that codes for protein production is inserted into a micro-organism host and as that host rapidly replicates, the protein is produced.
The most widely used host is E.coli, but this often contains toxins in its cell wall, called endotoxins, that are released when the cell breaks down, so products from the cell require purification and this can reduce the efficacy of the product.
Liz continues: “Clostridium is free of endotoxins, and so does not require purification. In some cases, ours is the best current solution for making certain types of recombinant protein.”
Applications for agriculture
Biocleave’s Commercial Director Dr Nathan Fairhurst explains the company currently has a BBSRC funded project with Rothamsted Research.
“Insect pheromones are used in traps to monitor insects, such as the Codling Moth, to identify the presence of adults to time spraying of orchards to kill the larvae. Rothamsted has identified a number of semiochemicals that have potential as biopesticides to lure insects away from crops or to disrupt their behaviour to prevent mating.”
“Rothamsted has done some limited field trials to demonstrate their efficacy but has been unable to scale production in a way to enable them to commercialise it. In this case it is because the enzymes needed are toxic to E. coli.”
“Our technology overcomes this issue. so, we are working with Rothamsted to develop these enzymes and demonstrate that they can be used in the production of semiochemicals.
“Rothamsted has connections with growers and the farming community and a spin-out company PheroSyn, which is starting to commercialise other semiochemicals so there is already a channel to market.”
Benefits of semiochemicals
Semiochemicals are used differently depending upon crop and insect, but they can either be used as attractants or as repellents – with attractant semiochemicals loaded into traps at the edges of the crop, and repellents applied in the centre of the crop to push the insects away from the crop into the traps. In other cases, you would just use one or the other.
Semiochemicals have big advantages over traditional insecticides, not only are they more targeted and can be used just when required, reducing the volumes of inputs required, but also the production process requires less energy and produces significantly less greenhouse gas emissions.
Nathan concludes: “Semiochemicals as biopesticides is an area that we’re really excited about, and Rothamsted are really excited about. They have identified the semiochemicals, and we’re providing the ability to make them.”
Nathan Fairhurst will be speaking at the Agri-TechE event ‘Advances in Breeding for Agriculture – New Tools for New Solutions’. The event will be looking at the application of genetic tools in breeding of livestock (including insects) and crops, as well as in cultivation of microbes. Nathan will be joined at the event by Helen Sang of the Roslin Institute; Thomas Ferrugia, CEO of Beta Bugs; Gilad Gershon, CEO of Tropic Bioscience; Ingo Hein, from the James Hutton Institute; and Mike Coffey, of the SRUC.