研究领域

Chemical Biology/Organic Chemistry/Enzymology: Discovery of new small molecules and biosynthetic pathways involved in microbial symbiotic interactions/elucidation of enzyme-catalyzed reaction mechanisms.

Much of what we know about bacteria has come from investigations of single, purified bacterial strains in nutrient-rich monocultures. In a natural setting, however, bacteria co-exist in astounding numbers and compete for limited resources. The discovery of staggering bacterial diversity in various habitats, such as soil or the human gut, and the impact of these communities on the environment or the host have highlighted the need to understand bacterial intra- and interspecies interactions. Bacteria use a wide range of small molecules to detect and respond to their environment and to communicate, collaborate, or compete with other microbes. The small molecules underlying this complex chemical dialogue, their functions, biosynthetic pathways, and the enzymatic reaction mechanisms involved in their production comprise the primary focus of our research efforts. Our goal is to decipher the molecular principles that govern bacterial intra- or interspecies interactions by discovering new small molecules and their functions within a biological context. The pathways and exotic enzymatic reaction mechanisms associated with the production of these compounds will also be examined. Because this group of small molecules has traditionally served as a prolific source of drugs or drug leads, our studies will also aim to identify therapeutically useful small molecules.

近期论文

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Seyedsayamdost, M. R., "High-throughput platform for the discovery of elicitors of silent bacterial gene clusters." Proceedings of the National Academy of Sciences of the United States of America 2014, 111 (20), 7266-7271. Seyedsayamdost, M. R.; Cleto, S.; Carr, G.; Vlamakis, H.; Vieira, M. J.; Kolter, R.; Clardy, J., "Mixing and Matching Siderophore Clusters: Structure and Biosynthesis of Serratiochelins from Serratia sp. V4." Journal of the American Chemical Society 2012, 134 (33), 13550-13553. Traxler, M. F.; Seyedsayamdost, M. R.; Clardy, J.; Kolter, R., "Interspecies modulation of bacterial development through iron competition and siderophore piracy." Molecular Microbiology 2012, 86 (3), 628-644. Adler, C.; Corbalan, N. S.; Seyedsayamdost, M. R.; Pomares, M. F.; de Cristobal, R. E.; Clardy, J.; Kolter, R.; Vincent, P. A., "Catecholate Siderophores Protect Bacteria from Pyochelin Toxicity." Plos One 2012, 7 (10). Chandler, J. R.; Truong, T. T.; Silva, P. M.; Seyedsayamdost, M. R.; Carr, G.; Radey, M.; Jacobs, M. A.; Sims, E. H.; Clardy, J.; Greenberg, E. P., "Bactobolin Resistance Is Conferred by Mutations in the L2 Ribosomal Protein." Mbio 2012, 3 (6). Seyedsayamdost, M. R.; Carr, G.; Kolter, R.; Clardy, J., "Roseobacticides: Small Molecule Modulators of an Algal-Bacterial Symbiosis." Journal of the American Chemical Society 2011, 133 (45), 18343-18349. Seyedsayamdost, M. R.; Traxler, M. F.; Zheng, S.-L.; Kolter, R.; Clardy, J., "Structure and Biosynthesis of Amychelin, an Unusual Mixed-Ligand Siderophore from Amycolatopsis sp. AA4." Journal of the American Chemical Society 2011, 133 (30), 11434-11437. Minnihan, E. C.; Seyedsayamdost, M. R.; Uhlin, U.; Stubbe, J., "Kinetics of Radical Intermediate Formation and Deoxynucleotide Production in 3-Aminotyrosine-Substituted Escherichia coli Ribonucleotide Reductases." Journal of the American Chemical Society 2011, 133 (24), 9430-9440. Seyedsayamdost, M. R.; Yee, C. S.; Stubbe, J., "Use of 2,3,5-F3Y-beta 2 and 3-NH2Y-alpha 2 To Study Proton-Coupled Electron Transfer in Escherichia coli Ribonucleotide Reductase." Biochemistry 2011, 50 (8), 1403-1411. Carr, G.; Seyedsayamdost, M. R.; Chandler, J. R.; Greenberg, E. P.; Clardy, J., "Sources of Diversity in Bactobolin Biosynthesis by Burkholderia thailandensis E264." Organic Letters 2011, 13 (12), 3048-3051.