Novel semiochemicals for crop protection through synthetic biology
Lead Research Organisation:
CARDIFF UNIVERSITY
Department Name: Chemistry
Abstract
Due to pressure on available farmland there is an urgent need for sustainably enhancing food crop production. One approach to combat insect pests is to repel or attract them using pheromone or other chemical signal baited traps, keeping them away from high-value crops.
Past attempts at the rational design of artificial insect pheromones have failed largely due to the highly specific nature of recognition processes in insects. Recently we have succeeded in producing modified aphid repellents/attractants through a strategic chemoenzymatic approach. One compound in particular proved to be a strong aphid attractant in small-scale laboratory experiments.
We intend to produce more of this compound to test its efficacy in field simulations and also to explore the activity of some new closely related compounds. Furthermore we will seek to commercialise the invention with prospective business partners.
Past attempts at the rational design of artificial insect pheromones have failed largely due to the highly specific nature of recognition processes in insects. Recently we have succeeded in producing modified aphid repellents/attractants through a strategic chemoenzymatic approach. One compound in particular proved to be a strong aphid attractant in small-scale laboratory experiments.
We intend to produce more of this compound to test its efficacy in field simulations and also to explore the activity of some new closely related compounds. Furthermore we will seek to commercialise the invention with prospective business partners.
Publications
Srivastava P
(2021)
Redesigning the Molecular Choreography to Prevent Hydroxylation in Germacradien-11-ol Synthase Catalysis
in ACS Catalysis
Johnson L
(2020)
Modular Chemoenzymatic Synthesis of Terpenes and their Analogues
in Angewandte Chemie
Demiray M
(2017)
Effiziente chemoenzymatische Synthese von Dihydroartemisinaldehyd
in Angewandte Chemie
Huynh F
(2020)
Accelerating Biphasic Biocatalysis through New Process Windows.
in Angewandte Chemie (International ed. in English)
Demiray M
(2017)
An Efficient Chemoenzymatic Synthesis of Dihydroartemisinic Aldehyde.
in Angewandte Chemie (International ed. in English)
Johnson LA
(2020)
Modular Chemoenzymatic Synthesis of Terpenes and their Analogues.
in Angewandte Chemie (International ed. in English)
Demiray M
(2019)
Harnessing enzyme plasticity for the synthesis of oxygenated sesquiterpenoids.
in Beilstein journal of organic chemistry
Tang X
(2018)
Concise synthesis of artemisinin from a farnesyl diphosphate analogue.
in Bioorganic & medicinal chemistry
Loizzi M
(2018)
Nucleophilic Water Capture or Proton Loss: Single Amino Acid Switch Converts d-Cadinene Synthase into Germacradien-4-ol Synthase.
in Chembiochem : a European journal of chemical biology
Valikhani D
(2020)
Immobilised Enzymes for Sesquiterpene Synthesis in Batch and Flow Systems
in ChemCatChem
Johnson L
(2025)
Engineering terpene synthases and their substrates for the biocatalytic production of terpene natural products and analogues
in Chemical Communications
Partridge S
(2021)
Iridoid Sex Pheromone Biosynthesis in Aphids Mimics Iridoid-Producing Plants
in Chemistry - A European Journal
Tang X
(2017)
Optimising Terpene Synthesis with Flow Biocatalysis
in European Journal of Organic Chemistry
Cheruiyot D
(2022)
Field evaluation of a new third generation push-pull technology for control of striga weed, stemborers, and fall armyworm in western Kenya
in Experimental Agriculture
Zhang Z
(2021)
Chemical Identity and Functional Characterization of Semiochemicals That Promote the Interactions between Rice Plant and Rice Major Pest Nilaparvata lugens.
in Journal of agricultural and food chemistry
Pickett J
(2016)
Plant volatile-mediated signalling and its application in agriculture: successes and challenges
in New Phytologist
Loizzi M
(2019)
Silent catalytic promiscuity in the high-fidelity terpene cyclase d-cadinene synthase.
in Organic & biomolecular chemistry
Pickett JA
(2019)
Removing constraints to sustainable food production: new ways to exploit secondary metabolism from companion planting and GM.
in Pest management science
Radadiya A
(2020)
Characterizing human odorant signals: insights from insect semiochemistry and in silico modelling
in Philosophical Transactions of the Royal Society B: Biological Sciences
Li W
(2021)
Overexpression of the homoterpene synthase gene, OsCYP92C21, increases emissions of volatiles mediating tritrophic interactions in rice.
in Plant, cell & environment
| Description | We have synthesised a range of new derivatives of a lead compound discovered during a previous award that received IP protection and we have worked to improve the scale at which these compounds can be synthesised. This work won Super Follow-On Funding from the BBSRC and has been succeeded by a further project aimed at taking this material to field trials. This work also led to several incidental publications as we worked to understand and improve the substrate selectivity of terpene cyclases for substrate analogues, including analogues that led to a truncated route to artemisinin. |
| Exploitation Route | We have received IP protection for molecules synthesised in the course of this award and hope to license this property once we have proven its utility in field trials. |
| Sectors | Agriculture Food and Drink |
| Description | The chemicals developed during this work are currently being tested for their ability to protect lettuce crops from insect pests. We hope to use a push-pull system to protect plants without having to treat the crop itself. The preliminary field trials have now been completed successfully and have been written up for publication and is awaiting submission until suitable licensees have been selected. Further samples are being synthesised beyond the grant for licensees to test in-house. |
| First Year Of Impact | 2025 |
| Sector | Agriculture, Food and Drink |
| Description | Advancing High Value Terpenoidal Semiochemicals for Crop Protection |
| Amount | £49,942 (GBP) |
| Organisation | Cardiff University |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 12/2023 |
| End | 10/2024 |
| Description | Super Follow-on Fund |
| Amount | £551,216 (GBP) |
| Funding ID | BB/R019681/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2018 |
| End | 04/2020 |
| Description | Industrial partner network |
| Organisation | BioPhero ApS |
| Country | Denmark |
| Sector | Private |
| PI Contribution | Through our collaborators Professor Owen Jones in particular but also Prof John Pickett who are well connected with the International Biocontrol Manufacturers' Association (IBMA)Home Page IBMA-GLOBAL International Biocontrol Manufacturers we have made contact and received favourable communication regarding potential firm collaboration from the players in the biocontrol industry and in particular those interested in semiochemicals, such as Shin Etsu, Suterra and Bedoukian as well as a number of other smaller participants in that field such as Provivi, BioPhero and Russell IPM Ltd. |
| Collaborator Contribution | Contact and discussions for potential future ventures made primarily by Prof Owen Jones and Prof John Pickett |
| Impact | None as yet but we remain active in preparing samples for industrial collaborators to employ on their own project. |
| Start Year | 2024 |
| Description | Industrial partner network |
| Organisation | Provivi |
| Country | United States |
| Sector | Private |
| PI Contribution | Through our collaborators Professor Owen Jones in particular but also Prof John Pickett who are well connected with the International Biocontrol Manufacturers' Association (IBMA)Home Page IBMA-GLOBAL International Biocontrol Manufacturers we have made contact and received favourable communication regarding potential firm collaboration from the players in the biocontrol industry and in particular those interested in semiochemicals, such as Shin Etsu, Suterra and Bedoukian as well as a number of other smaller participants in that field such as Provivi, BioPhero and Russell IPM Ltd. |
| Collaborator Contribution | Contact and discussions for potential future ventures made primarily by Prof Owen Jones and Prof John Pickett |
| Impact | None as yet but we remain active in preparing samples for industrial collaborators to employ on their own project. |
| Start Year | 2024 |
| Description | Industrial partner network |
| Organisation | Russell IPM (Integrated Pest Management) |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Through our collaborators Professor Owen Jones in particular but also Prof John Pickett who are well connected with the International Biocontrol Manufacturers' Association (IBMA)Home Page IBMA-GLOBAL International Biocontrol Manufacturers we have made contact and received favourable communication regarding potential firm collaboration from the players in the biocontrol industry and in particular those interested in semiochemicals, such as Shin Etsu, Suterra and Bedoukian as well as a number of other smaller participants in that field such as Provivi, BioPhero and Russell IPM Ltd. |
| Collaborator Contribution | Contact and discussions for potential future ventures made primarily by Prof Owen Jones and Prof John Pickett |
| Impact | None as yet but we remain active in preparing samples for industrial collaborators to employ on their own project. |
| Start Year | 2024 |
| Description | Rothamstead Research |
| Organisation | Rothamsted Research |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We have provided research materials. |
| Collaborator Contribution | They have provided testing facilities and expertise. |
| Impact | Novel Olfactory Ligands via Terpene Synthases Sabrina Touchet, Keith Chamberlain, Christine M. Woodcock, David J. Miller, Michael A. Birkett, John A. Pickett and Rudolf K. Allemann Chem. Commun., 51, 7550-7553 (2015). DOI:10.1039/C5CC01814E |
| Start Year | 2010 |
| Title | OLFACTORY LIGANDS |
| Description | The invention provides analogues of (S)-germacrene D analogue which have improved insect repellent properties compared to (S)-germacrene D analogue or which have insect attractant properties. |
| IP Reference | US2018271089 |
| Protection | Patent granted |
| Year Protection Granted | 2018 |
| Licensed | Commercial In Confidence |
| Impact | Further development has been supported by Super Follow-On Funding. |
| Description | Next Generation Insects Chemical Ecology: Part I Career path in chemical ecology |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Undergraduate students |
| Results and Impact | Prof John Pickett was invited to take part in an event entitled Next Generation Insects Chemical Ecology on 29/11/2023 at the Max Planck Institute for Chemical Ecology, Jena, Germany. As part of this event he presented to the students highlights from his long illustrious career and showed how opportunities for a career in the chemical ecology industry have never been brighter. As part of this presentation our joint work on terpene synthases aimed at producing modified semiochemicals for crop protection was showcased towards the end. |
| Year(s) Of Engagement Activity | 2023 |
| Description | Opportunities for increased sustainability of grassland food production and carbon sequestration |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Prof Pickett and myself (RKA) travelled to the University of Wyoming to explore possible academic and commercial opportunities as part of a delegation from Cardiff University. The purpose of the visit was part of a wider initiative to build a partnership between Cardiff University and the University of Wyoming, USA. Prof Pickett presented a variety of proposals for collaborations that included our work on germacrene D synthase and our modular chemoenzymatic synthesis of terpenoids using promiscuous kinases. Talks are ongoing on possible future collaborations. |
| Year(s) Of Engagement Activity | 2023 |
| Description | Opportunities in Crop Protection from plant-produced repellent (4R, 7R)-zingiberene |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Industry/Business |
| Results and Impact | Presentation by Prof John Pickett to BridgeFarm Biosciences as part of a site visit aimed at increasing network and promoting our research for potential future collaboration and commercialisation. |
| Year(s) Of Engagement Activity | 2025 |
| Description | Terpene Synthases: Structure, Function and Exploitation. |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Professional Practitioners |
| Results and Impact | This was a research seminar at Nottingham University, February 2024 conducted by Prof John Pickett. The general theme of the presentation was the use of terpene synthases to generated bioactive terpenoid semiochemicals for use in environmentally benign crop protection. Material related to the modular generation of terpenes through the use of promiscuous kinases and terpene synthase to generate germacrene D analogues, and (4R,7R)-zingiberene and analogues including field testing of our germacrene D/14,15-dimethylgermacrene D push-pull strategy for protection of lettuce from aphids. |
| Year(s) Of Engagement Activity | 2024 |
| Description | Terpenoids anticancer compounds: discovery and production |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | This was a presentation by Prof John Pickett, delivered online through invitation from Prof Gilles Favre of Toulouse Cancer Research Centre to the staff there plus visitors from CAELIMP. Amongst the material presented was the work developed by the collaboration between the Allemann and Pickett groups on modular terpene synthesis using promiscuous kinases and showcased the work performed on germacrene D synthase, and (4R,7R)-zingiberene synthase. Further material included our work on water capture. |
| Year(s) Of Engagement Activity | 2024 |
| Description | Video for Trio Sci Cymru on Youtube |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Schools |
| Results and Impact | A BSc project student (supervised by David Miller, CoI on this grant) produced a video in collaboration with Trio Sci Cymru to disseminate the idea of semiochemical based crop protection as a sustainable, environmentally benign, methodology as opposed to use of large quantities of pesticides through spraying. This video is professional in look and has been viewed 759 times on its still existing YouTube channel. Trio Sci Cymru were a welsh government funded organisation whose aim was to encourage engagement in science between school and university level students in STEM subjects. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.youtube.com/watch?v=Pju-5zQb6gg |