Biochemistry and genetics of sulfur amino acid metabolism

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The long-term goals of my research program include understanding the regulation of the pathways of cysteine and methionine biosynthesis and the basis of substrate and reaction specificity in the enzymes of the transsulfuration pathways, which catalyze the inter-conversion of these two sulfur-containing amino acids. This research encompasses three inter-related projects with biotechnological, agricultural and environmental applications. (1) During the next granting cycle, my students and I will continue to investigate the structurally-similar, but mechanistically-distinct enzymes of the transsulfuration pathways. The identification of determinants of reaction specificity in these enzymes, resulting from this work, will contribute to our understanding of how pyridoxal 5'-phosphate-dependent enzymes control the chemistry of this catalytically-versatile cofactor, thereby facilitating the design of customized biocatalysts for the production of novel amino acid compounds. (2) Grain legumes are important Canadian export crops and staple foods in many countries. However, they are deficient in the essential amino acid methionine, from the perspective of human nutrition. My lab is exploring the mechanisms that regulate the flow of metabolites in the methionine biosynthetic pathway of chickpea. The results of this work will enable the subtle genetic engineering of grain legumes required to improve their nutritional quality. (3) The amino acids cysteine and methionine are the precursors of compounds, such as glutathione, phytochelatins and nicotianamine, which can coordinate heavy metal ions and are involved in their translocation and sequestration in plants. The conservative estimate of 30,000 contaminated sites in Canada demonstrates the urgent need for developing low-cost remediation technologies. My lab is exploring the effect of cadmium exposure on the expression levels of genes of the sulfur assimilation and metabolism pathways, which produce sulfur-rich compounds that chelate heavy metals, in the hyperaccumulator species Brassica juncea. The identification of genes linked to hyperaccumulation will facilitate the design of plant varieties with improved capacity for phytoremediation.