This research proposal describes the development of a research program to study the biogenesis of Arabidopsis phytoalexins. We will begin by investigating the biosynthetic pathway of camalexin, a phytoalexin produced as part of the induced defense response. The first part of our two-phase plan for studying Arabidopsis phytoalexin pathways will focus on the identification of camalexin biosynthetic genes through a collaboration with the Ausubel lab at MGH. During this training period, I will attend relevant meetings and workshops, and I will consult regularly with three senior advisors to establish skills required for timely advance of the project. During the second, independent phase of the project I will biochemically characterize candidate phytoalexin pathway enzymes implicated by the data gathered during phase one. I expect that this work will serve as a springboard for the formulation of a new research program that uses a combination of genetics, chemistry, and biochemistry to elucidate secondary metabolite biosynthetic pathways in plants. A deeper understanding of these pathways will not only illuminate the molecular details of host-pathogen interactions, but it is also likely to have an important impact on human health, given the strong track record of plant natural products as clinically-used medicines.
Plants produce a wealth of secondary metabolites for defense against destructive pests. The research program outlined in this proposal explores components of plant immune response pathways as well as the production, distribution, and metabolism of the contributing small molecules. These compounds are contained in commonly consumed vegetables and have been found to have beneficial effects on human health.
Lau, Warren; Sattely, Elizabeth S (2015) Six enzymes from mayapple that complete the biosynthetic pathway to the etoposide aglycone. Science 349:1224-8 |
Klein, Andrew P; Sattely, Elizabeth S (2015) Two cytochromes P450 catalyze S-heterocyclizations in cabbage phytoalexin biosynthesis. Nat Chem Biol 11:837-9 |
Rajniak, Jakub; Barco, Brenden; Clay, Nicole K et al. (2015) A new cyanogenic metabolite in Arabidopsis required for inducible pathogen defence. Nature 525:376-9 |
Lau, Warren; Fischbach, Michael A; Osbourn, Anne et al. (2014) Key applications of plant metabolic engineering. PLoS Biol 12:e1001879 |
Anarat-Cappillino, Gülbenk; Sattely, Elizabeth S (2014) The chemical logic of plant natural product biosynthesis. Curr Opin Plant Biol 19:51-8 |
Dunn, Briana J; Watts, Katharine R; Robbins, Thomas et al. (2014) Comparative analysis of the substrate specificity of trans- versus cis-acyltransferases of assembly line polyketide synthases. Biochemistry 53:3796-806 |
Fitzgerald, Jay T; Charkoudian, Louise K; Watts, Katharine R et al. (2013) Analysis and refactoring of the A-74528 biosynthetic pathway. J Am Chem Soc 135:3752-5 |
Klein, Andrew P; Anarat-Cappillino, Gülbenk; Sattely, Elizabeth S (2013) Minimum set of cytochromes P450 for reconstituting the biosynthesis of camalexin, a major Arabidopsis antibiotic. Angew Chem Int Ed Engl 52:13625-8 |