Area of research
Clinical Biochemistry · Molecular Biology
Research interest
Research Interests The Begley Group is interested in the mechanistic chemistry and enzymology of complex organic transformations, particularly those found on the vitamin biosynthetic pathways. We are currently working on the biosynthesis of thiamin, molybdopterin, pyridoxal phosphate and menaquinone. Our research involves a combination of molecular biology, protein biochemistry, organic synthesis and structural studies and provides a strong training for students interested in understanding the organic chemistry of living systems and in pursuing careers in biotechnology, drug design or academia. Thiamin pyrophosphate plays a key role in the stabilization of the acyl carbanion synthon in carbohydrate and amino acid metabolism. The biosyntheses of the thiamin pyrimidine and thiazole are complex and are different from any of the characterized chemical or biochemical routes to these heterocycles. We are particularly interested in cellular physiology and the mechanistic enzymology of thiamin biosynthesis. As an example of one of the complex transformations on this pathway, the figure below shows the structure of the pyrimidine synthase catalyzing the complex rearrangement of aminoimidazole ribotide (left) to the thiamin pyrimidine (right).
Mehta, A. P.; Hanes, J. W.; Abdelwahed, S. H.; Hilmey, D. G.; Hanzelmann, P.; Begley, T. P.: Catalysis of a New Ribose Carbon-Insertion Reaction by the Molybdenum Cofactor Biosynthetic Enzyme MoaA. Biochemistry 2013 , 52 , 1134-1136
— 2013cited by 0position: selected
Mehta, A. P.; Abdelwahed, S. H.; Begley, T. P.: Molybdopterin Biosynthesis: Trapping an Unusual Purine Ribose Adduct in the MoaA-Catalyzed Reaction. Journal of the American Chemical Society 2013 , 135 , 10883-10885
— 2013cited by 0position: selected
BOOK: Cofactor Chemistry, Volume 7 of Comprehensive Natural Products Chemistry, 2010. Edited by Tadhg P. Begley
— 2010cited by 0position: selected
BOOK: Encyclopedia of Chemical Biology, Volumes 1-4, (2009), Edited by Tadhg P. Begley
— 2009cited by 0position: selected
Menaquinone Biosynthesis via the Futalosine Pathway
Menaquinone biosynthesis via the futalosine pathway
New Radical SAM Enzymes in Menaquinone Biosynthesis
U.S.-Japan Joint Seminar: Learning Nature's Strategies for Making Natural Products: Pathways, Mechanisms, Functional Genomics, and Biosynthetic Applications