Begley, Tadhg individual record
Distinguished Professor
Positions:
overview

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).

selected publications
Academic Articles236
  • Joshi, S., Fedoseyenko, D., Sharma, V., Nesbit, M. A., Britt, R. D., & Begley, T. P. (2021). Menaquinone Biosynthesis: New Strategies to Trap Radical Intermediates in the MqnE-Catalyzed Reaction.. Biochemistry. 60(21), 1642-1646.
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  • Manion-Sommerhalter, H. R., Fedoseyenko, D., Joshi, S., & Begley, T. P. (2021). Menaquinone Biosynthesis: The Mechanism of 5,8-Dihydroxy-2-naphthoate Synthase (MqnD).. Biochemistry. 60(25), 1947-1951.
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  • Tao, L., Pattenaude, S. A., Joshi, S., Begley, T. P., Rauchfuss, T. B., & Britt, R. D. (2020). Radical SAM Enzyme HydE Generates Adenosylated Fe(I) Intermediates En Route to the [FeFe]-Hydrogenase Catalytic H-Cluster.. J Am Chem Soc. 142(24), 10841-10848.
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  • Sayler, R. I., Stich, T. A., Joshi, S., Cooper, N., Shaw, J. T., Begley, T. P., Tantillo, D. J., & Britt, R. D. (2019). Trapping and Electron Paramagnetic Resonance Characterization of the 5'dAdo• Radical in a Radical S-Adenosyl Methionine Enzyme Reaction with a Non-Native Substrate.. ACS Cent Sci. 5(11), 1777-1785.
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Chapters6
  • Adak, S., & Begley, T. P. (2019). Flavin-N5-oxide intermediates in dibenzothiophene, uracil, and hexachlorobenzene catabolism.. MACROMOLECULAR CRYSTALLOGRAPHY, PT D. Methods in Enzymology. 455-468. Elsevier.
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  • Joshi, S., Fedoseyenko, D., Mahanta, N., & Begley, T. P. (2018). Aminofutalosine Synthase (MqnE): A New Catalytic Motif in Radical SAM Enzymology.. MACROMOLECULAR CRYSTALLOGRAPHY, PT D. Methods in Enzymology. 179-198. Elsevier.
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  • Wang, Y., Schnell, B., Müller, R., & Begley, T. P. (2018). Iterative Methylations Resulting in the Biosynthesis of the t-Butyl Group Catalyzed by a B12-Dependent Radical SAM Enzyme in Cystobactamid Biosynthesis.. MACROMOLECULAR CRYSTALLOGRAPHY, PT D. Methods in Enzymology. 199-216. Elsevier.
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  • Bhandari, D. M., Fedoseyenko, D., & Begley, T. P. (2018). Mechanistic Studies on the Radical SAM Enzyme Tryptophan Lyase (NosL).. MACROMOLECULAR CRYSTALLOGRAPHY, PT D. Methods in Enzymology. 155-178. Elsevier.
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  • Burns, K. E., & Begley, T. P. (2013). Mec+ Peptidase (Mycobacterium tuberculosis). Handbook of Proteolytic Enzymes. 1567-1570. Elsevier.
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Conference Papers8
  • Decamps, L., Benjdia, A., Berteau, O., Decamps, L., Benjdia, A., Berteau, O., ... Latour, J. (2014). One enzyme for two radical reactions: Deciphering the mechanism of a novel radical SAM enzyme critical for F-420 cofactor biosynthesis. JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY. 19, S308-S308.
  • Abdelwahed, S. H., & Begley, T. P. (2013). Biosynthesis of dimethylbenzimidazole: Catalysis of a remarkable flavin degradation reaction. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY. 246,
  • Hanes, J. W., Burns, K. E., Hilmey, D. G., Chatterjee, A., Dorrestein, P. C., Keresztes, I., & Begley, T. P. (2008). BIOL 155-Mechanistic studies on pyridoxal phosphate synthase: The reaction pathway leading to a chromophoric intermediate. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY. 235,
  • Mueller, I. B., Eschbach, M., Begley, T. P., Walter, R. D., & Wrenger, C. (2008). Vitamin B1 synthesis and salvage in Plasmodium falciparum.. INTERNATIONAL JOURNAL FOR PARASITOLOGY. 38, S43-S43.
  • Begley, T. P. (2005). Tryptophan catabolism: Gene identification and mechanistic studies. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY. 230, U587-U587.
chaired theses and dissertations
Email
begley@tamu.edu
First Name
Tadhg
Last Name
Begley
mailing address
Texas A&M University; Chemistry Department; 3255 TAMU
College Station, TX 77843-3255
USA