Scientific research into new natural products at the John Innes Centre

Plants produce a huge array of different types of chemicals, and these are the chemicals that we associate with the scents and the colours and the flavours of different types of plant species. And they also provide protection against attack by pests and diseases. Of course, humans exploit these chemicals for a huge range of applications, including as drugs, flavours, fragrances, and many other useful purposes. One of the groups of compounds that people are aware of as contributing to health are anthocyanins. These are the bluey, purpley, reddy colours that are found in some fruits, particularly berries. And those are known to reduce risk of cardiovascular disease and have some anti-cancer properties as well. They're also made extensively by flowers to attract pollinators. This is antirhinum, and this is making anthocyanins in the flower to attract bee pollinators. So they have beneficial effects for plants as well. So what we've been interested in doing is trying to move the production of anthocyanins into tomato. Now, tomato is red because it produces lycopene in the fruit. Lycopene is not the same type of chemical as anthocyanins. So we took the genes from antirhinum that switch on the production of anthocyanins and moved those into tomato, and the result was that we got these plants which produce purple fruit. And they're rich in anthocyanins, and they're at the same levels that you get in many of the berries. So we've then undertaken tests to compare the beneficial effects of the purple tomatoes compared to red tomatoes. We fed them to cancer-prone mice, which develop tumours and die very quickly. And a supplement of 10% of the diet with the purple tomatoes extended the lifespan of the mice by 30% compared to the red controlled tomatoes, so proving the health beneficial properties of the anthocyanins. Many people either can't afford or don't have access to berries all the year round and don't eat enough of them. They're expensive, and they're very seasonal. So we're hoping that because tomato is the most widely consumed vegetable crop, that we may be able to make products that are enriched in the healthy chemicals so that people can get some of these beneficial chemicals in their regular food. So one of the things that we're trying to understand is how plants make certain types of antimicrobial compound that provide protection against important diseases such as take-all. Take-all is a soil-borne disease that attacks wheat and costs the UK alone a huge amount in yield losses, in the region of £30-120 million a year. If we can understand why plants such as oat are able to make antimicrobial chemicals that provide protection against take-all, while wheat does not, then we might be able to modify wheat so that it produces antimicrobial compounds that confer disease resistance. So some plants produce compounds that are toxins, and they use those essentially as defence mechanisms. One example is in lotus japonicus, where the leaves in particular produce high levels of compounds called cyanogenic glucosides. When an insect eats a leaf that has made cyanogenic glucosides, there are enzymes that are secreted that break down the cyanogenic glucosides and release cyanide, and so those are toxic to the insect predators. Of course these compounds can be toxic to humans as well, and a good example of this is in cassava, where the roots, which are the part that's eaten, also contain high levels of cyanogenic glucosides, and if you don't prepare the cassava correctly, which involves soaking for two days and then boiling, then you can get an irreversible neurological damage, which is called konzo, and people are much more susceptible to the effects of konzo when they are nutritionally challenged, when they haven't had enough to eat, and the plants themselves make more cyanogenic glucosides when they're stressed, particularly under drought conditions. So we were very interested in trying to determine whether we could influence the production of cyanogenic glucosides, and for that we used a model plant, lotus japonicus, and we mutagenized a population of plants and then grew up about 45,000 plants to screen for mutants that didn't make cyanogenic glucosides. We took about two weeks to screen them, and we got about 40 mutants that either didn't make or didn't break down the cyanogenic glucosides. So that was really encouraging to show that you could mutagenize the pathway and eliminate it, and really leads to the possibilities that we might be able to do something similarly in cassava. There are people that have said, pointed out, that if you remove the cyanogenic glucosides, then you remove a natural defense mechanism, and it could make the cassava plants, varieties that you could generate, much more susceptible to pathogen infection and possibly disease. But we think from the results that we got in lotus that we could inhibit the production of cyanogenic glucosides in the roots, but not in the leaves, so that they would maintain some of their resistance, at least to insect predators. So at John Innes, in the area of natural products, there's work not only on plants, but also on microbes, which also produce a huge array of different types of chemicals. And these chemicals, we think, are associated with the ability of plants and microbes to survive in different environments. By understanding the mechanisms that enable microbes and plants to evolve new pathways and to make new compounds, we can exploit this information in a range of different ways for crop improvement, for discovery of new antibiotics and other bioactives, and for a whole range of other purposes.