Genetic engineers have created various types of biotech crops, including corn and cotton resistant to insects. But some other possibilities, such as plants that could make cancer drugs, have yet to yield to the bioengineer’s bag of tricks. Scientists say that the relatively new technique of metabolomics – the analysis of all the metabolites in an organism – could provide the genetic insight needed to make these highly desirable products.
While genomics and proteomics focus on the DNA and proteins present in an organism, metabolomics analyzes the end products – such as sugars, fats, and peptides – of all the biochemical reactions taking place in a cell. Researchers say these end-product molecules may provide details into how genes affect the observable characteristics of a plant, such as how fast it grows or how resistant it is to cold.
Basil Nikolau, director of the Center for Designer Crops at Iowa State University, will lead a team of researchers at Iowa State and six other institutions using metabolomics to elucidate the function of 100 genes in the mustard plant, Arabidopsis, a model organism. During the two-year pilot project, funded by the National Science Foundation, scientists will study different strains of the plant that each have a single gene “knocked out.” In order to understand the relationship between genes and metabolites, researchers will systematically analyze how the loss of this gene changes the level of different metabolites.
The findings will shed light on how plants grow and develop, but could also have major agricultural applications in producing novel routes to various compounds. For example, genetic engineers have been unable to make plants that produce high levels of Taxol, an anti-cancer compound extracted from the Pacific yew tree. Such a plant could provide a cheaper, more efficient way to make the drug.
One reason Taxol production is difficult to engineer in plants is that the compound is synthesized in approximately 30 different steps. “With metabolomics, you can figure out the individual steps in the pathway, which in principle should suggest a number of ways to suppress or enhance gene expression to produce that compound,” says L. Val Giddings, vice president for food and agriculture at the Biotechnology Industry Organization in Washington, DC.
The metabolomics approach could also help researchers better manipulate existing pathways in plants. Lloyd Sumner, a plant biochemist with The Samuel Roberts Noble Foundation in Oklahoma, has been trying to engineer a plant to produce more isoflavenoids, an antioxidant that may help prevent heart disease and cancer. Scientists have been studying the pathway for 40 years and have identified many of the key genes. But when Sumner and team tried to engineer plants to make more of the healthful compound, they discovered that the desired isoflavenoid was converted into a useless form a few steps later along the biochemical pathway. “Metabolomics helps us understand intentional and unintentional effects [of altering genes],” he says. “When you try to put a gene into a plant to do a specific thing, you don’t always get the effect you want.”
While a few agricultural biotechnology companies are using metabolomics on a small-scale, the Iowa State project is the first large-scale metabolomics program in plants. Giddings says the project is “just what the doctor ordered” to test the technology for broader use.