Limonoids discovery could raise use of Bee-friendly Crop Protection

Date:02-20-2023

Collaborative research between the John Innes Centre (JIC) and Stanford University has discovered how certain plant families, including mahogany and citrus, are able to make limonoids, valuable organic chemicals which include bee-friendly insecticides and also have potential as anti-cancer drugs.

The JIC team used genomic tools to assemble a chromosome level genome for Chinaberry (Melia azedarach), within which they found the genes encoding 10 additional enzymes required to produce the azadirachtin precursor, azadirone.

In parallel, the team working at Stanford were able to find the 12 additional enzymes required to make khidalactone A.

Expressing these enzymes in Nicotiana benthamiana enabled their characterisation, with the help of both liquid chromatography–mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy allowing molecular level analysis of samples.

″By finding the enzymes required to make limonoids, we have opened the door to an alternate production source of these valuable chemicals,″ explained Dr Hannah Hodgson, co-first author of the paper and a postdoctoral scientist at the JIC.

Until now limonoids, a type of triterpene, could only be produced by extraction from plant material. Dr Hodgson continued: ″Their structures are too complicated to efficiently make by chemical synthesis. With the knowledge of the biosynthetic pathway, it is now possible to use a host organism (such as N.benthamiana) to produce these compounds.″ she added. Production of the chemicals in commonly used host plants could increase supplies of limonoids in a more sustainable way, which in turn could enable the more widespread use of azadirachtin, the anti-insect limonoid obtained from the neem tree and used in commercial and traditional crop protection. Azadirachtin is an effective, fast degrading, bee-friendly option for crop protection but is not widely used due to limited supply.

JIC group leader and co-corresponding author of the study Professor Anne Osbourn, said: ″Plants make a wide variety of specialised metabolites that can be useful to humans. We are only just starting to understand how plants make complex chemicals like limonoids. Prior to this project, their biosynthesis and the enzymes involved were completely unknown, now the door is open for future research to build on this knowledge, which could benefit people in many ways.″

Another example of a high value limonoid which the team hopes to produce is the anti-cancer drug candidate nimbolide and they are confident in the potential of their work in the understanding of new activities for limonoids that have not yet been investigated.

The team at the John Innes Centre were funded by Syngenta and BBSRC via an industrial partnership award. The research was published in Science.