Discovery of a novel amino acid race mase through exploration of natural variation in Arabidopsis thaliana, Proc Natl Acad Sci U S A. 2015 Aug 31, Strauch RC1, Svedin E2, Dilkes B2, Chapple C3, Li X4.
- 1Plants for Human Health Institute, North Carolina State University, Kannapolis, NC 28081; Department of Plant and Microbial Biology, North Carolina State University, Raleigh, NC 27695;
- 2Department of Horticulture and Landscape Architecture, Purdue University, West Lafayette, IN 47907;
- 3Department of Biochemistry, Purdue University, West Lafayette, IN 47907.
- 4Plants for Human Health Institute, North Carolina State University, Kannapolis, NC 28081; Department of Plant and Microbial Biology, North Carolina State University, Raleigh, NC 27695; email@example.com.
Plants produce diverse low-molecular-weight compounds via specialized metabolism. Discovery of the pathways underlying production of these metabolites is an important challenge for harnessing the huge chemical diversity and catalytic potential in the plant kingdom for human uses, but this effort is often encumbered by the necessity to initially identify compounds of interest or purify a catalyst involved in their synthesis. As an alternative approach, we have performed untargeted metabolite profiling and genome-wide association analysis on 440 natural accessions of Arabidopsisthaliana. This approach allowed us to establish genetic linkages between metabolites and genes. Investigation of one of the metabolite-gene associations led to the identification of N-malonyl-d-allo-isoleucine, and the discovery of a novel amino acid racemase involved in its biosynthesis. This finding provides, to our knowledge, the first functional characterization of a eukaryotic member of a large and widely conserved phenazine biosynthesis protein PhzF-like protein family. Unlike most of known eukaryotic amino acid racemases, the newly discovered enzyme does not require pyridoxal 5′-phosphate for its activity. This study thus identifies a new d-amino acid racemase gene family and advances our knowledge of plant d-amino acid metabolism that is currently largely unexplored. It also demonstrates that exploitation of natural metabolic variation by integrating metabolomics with genome-wide association is a powerful approach for functional genomics study of specialized metabolism.