Collaborative Research: Production of known and novel, safe, and biodegradable pyrethrin-type insecticides in tomato

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1565355/1565232 Pichersky/Last Pyrethrins are a group of six similar natural insecticides synthesized by the flowers of the plant Tanacetum cinerariifolium, a relative of chrysanthemum. Pyrethrins are extremely safe to humans and to domestic and barn animals, and have been used to fight malaria and other insect-borne diseases. They are also biodegradable and non-persistent in the environment, preventing the appearance of pyrethrin-resistant insects. Pyrethrins are currently obtained by growing the plants until they bloom, collecting the flowers, and extracting the compounds from dry petals. Because the concentration of pyrethrins in the petals is low, overall pyrethrin yield is low, the amount available for sale is limited, and the price is high. The researchers will employ genes from T. cinerariifolium and other plants to reconstruct the biosynthetic pathway leading to the six natural pyrethrins, as well as to create new variant pyrethrins, in tomato that have a high capacity for synthesizing an early precursor of pyrethrins. Thus, this work aims to develop tomato as a system for making high-value organic compounds in general, and increase the available range of natural, safe, and biodegradable insecticides. In addition, this research will provide interdisciplinary training opportunities in genetic engineering, plant biochemistry, analytical chemistry, and molecular biology to undergraduate and graduate students as well as post-doctoral researchers. Furthermore, the researchers will engage in outreach programs to young people and adults to describe the research project, its results, and potential societal benefits. Pyrethrins are natural insecticides synthesized by the flowers of the plant Tanacetum cinerariifolium (Asteraceae). A pyrethrin is an ester made up of one of two monoterpenoid acids (chrysanthemic and pyrethric acids) and one of three alcohols derived from jasmonic acid (pyrethrolone, cinerolone, and jasmolone). The researchers will recreate the biosynthetic pathway to chrysanthemic acid in tomato, which by itself does not have the genes specifying the synthesis of chrysanthemic acid but makes the early precursor dimethylallyl diphosphate (DMAPP). Tomato was chosen as a production system because two of its organs, fruits and trichomes, make DMAPP in large amounts. The pathway will be streamlined by identifying and deploying genes and enzymes from T. cinerariifolium and other plant species that efficiently convert DMAPP to chrysanthemic acid, and by identifying and inhibiting genes and enzymes that divert pathway intermediates to non-productive side-products. The project will also examine if the engineered tomato lines produce esters of chrysanthemic acid, and develop approaches to engineer tomato to make natural pyrethrin esters as well as novel esters of chrysanthemic acid for testing possible insecticidal properties. Finally, natural pyrethrins will be produced enzymatically and non-enzymatically in vitro with tomato-produced chrysanthemic acid. This work will result in the high-yield production of highly valuable natural and safe pesticides. It will also advance the general goal of better understanding of plant metabolism so that the production of specific compounds in plants by genetic engineering techniques can become more predictable.This award by the Biotechnology and Biochemical Engineering Program of the CBET Division is co-funded by the Systems and Synthetic Biology Program of the Division of Molecular and Cellular Biosciences.