Mohammad R. Seyedsayamdost
Contact:
Seyedsayamdost Group Website
Mohammad R. Seyedsayamdost
Professor of Chemistry
[email protected]
Frick Laboratory, 333
609-258-5941
Faculty Assistant:
Angela Dolce
[email protected]
Frick Laboratory, A87
609-258-5075
Research Focus
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.
Honors
Dean For Research Award for Distinguished Innovation (2022)
MacArthur Fellow (2020)
Protein Science Young Investigator Award (2020)
NSF CAREER Award (2019)
ACS Pfizer Award in Enzyme Chemistry (2018)
Camille Dreyfus Teacher-Scholar (2018)
Burrough Wellcome Investigator (2017)
Princeton Intellectual Property Accelerator Award (2016)
NIH Director’s New Innovator Award (2015)
Princeton Environmental Institute Innovative Research Award (2015)
Pew Biomedical Scholars Award (2014)
Searle Scholars Award (2014)
NIH Pathway to Independence Award (K99/R00, 2012)
Novartis & Life Sciences Research Foundation Fellowship (2008)
Selected Publications
Kayrouz, C. M.; Huang, J.; Hauser, N.; Seyedsayamdost, M. R. Biosynthesis of Selenium-Containing Small Molecules in Diverse Microorganisms. Nature 2022, 610, 199–204.
Clark, K. A.; Covington, B. C.; Seyedsayamdost, M. R. Biosynthesis-Guided Discovery Reveals Enteropeptins as Alternative Sactipeptides Containing N-Methylornithine. Nat. Chem. 2022, 14, 1390–1398.
Bushin, L. B.; Covington, B. C.; Clark, K. A.; Caruso, A.; Seyedsayamdost, M. R. Bicyclostreptins are Radical SAM Enzyme-modified Peptides with Unique Cyclization Motifs. Nat. Chem. Biol. 2022, I18, 1135–1143.
Covington, B. C.; Seyedsayamdost, M. R. Vitamin B3 Triggers Biosynthesis of Secondary Metabolite Dormancy Signals in Streptococcus suis. J. Am. Chem. Soc. 2022, 144, 14997–15001.
Li, A.; Okada, B. K.; Rosen, P. C.; Seyedsayamdost, M. R. Piperacillin Triggers Virulence Factor Biosynthesis via the Oxidative Stress Response in Burkholderia thailandensis. Proc. Natl. Acad. Sci. USA 2021, 118, e2021483118.
Covington, B. C.; Xu, F.; Seyedsayamdost, M. R. A Natural Product Chemist’s Guide to Unlocking Silent Biosynthetic Gene Clusters. Annu. Rev. Biochem. 2021, 90, 763–788.
Bushin, L. B.; Covington, B. C.; Rued, B. E.; Federle, M. J.; Seyedsayamdost, M. R. Discovery and Biosynthesis of Streptosactin, a Sactipeptide with an Alternative Topology Encoded by Commensal Bacteria in the Human Microbiome. J. Am. Chem. Soc. 2020, 142, 16265–16275.
Forneris, C.C.*; Nguy, A. K. L.*; Seyedsayamdost, M. R. Mapping and Exploiting the Promiscuity of OxyB toward Biocatalytic Production of Vancomycin Aglycone Variants. ACS Catal. 2020, 10, 9287–9298.
Caruso, A.; Martinie, R. J.; Bushin, L. B.; Seyedsayamdost, M. R. Macrocyclization via an Arginine-Tyrosine Crosslink Broadens the Reaction Scope of Radical SAM Enzymes. J. Am. Chem. Soc. 2019, 141, 16610–16614.
Moon, K.; Xu, F.; Seyedsayamdost, M. R. Cebulantin, A Cryptic Lanthipeptide Antibiotic Uncovered via Bioactivity-Coupled HiTES. Angew. Chem. Int. Ed. 2019, 58, 5973–5977.
Xu, F.; Wu, Y.; Zhang, C.; Davis, K. M.; Moon, K.; Bushin, L. B.; Seyedsayamdost, M. R. A Genetics-Free Method for High-Throughput Discovery of Cryptic Microbial Metabolites. Nat. Chem. Biol. 2019, 15, 161–168.
Forneris, C. C.; Seyedsayamdost, M. R. In Vitro Reconstitution of OxyC Activity Enables Total Chemo-Enzymatic Syntheses of Vancomycin Aglycone Variants. Angew. Chem. Int. Ed. 2018, 57, 8048–8052.
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.
Fernandes, N.; Case, R. J.; Longford, S. R.; Seyedsayamdost, M. R.; Steinberg, P. D.; Kjelleberg, S.; Thomas, T., “Genomes and Virulence Factors of Novel Bacterial Pathogens Causing Bleaching Disease in the Marine Red Alga Delisea pulchra.” Plos One 2011, 6 (12).
Seyedsayamdost, M. R.; Case, R. J.; Kolter, R.; Clardy, J., “The Jekyll-and-Hyde chemistry of Phaeobacter gallaeciensis.” Nature Chemistry 2011, 3 (4), 331-335.
Seyedsayamdost, M. R.; Chandler, J. R.; Blodgett, J. A. V.; Lima, P. S.; Duerkop, B. A.; Oinuma, K.-I.; Greenberg, E. P.; Clardy, J., “Quorum-Sensing-Regulated Bactobolin Production by Burkholderia thailandensis E264.” Organic Letters 2010, 12 (4), 716-719.
Seyedsayamdost, M. R.; Argirevic, T.; Minnihan, E. C.; Stubbe, J.; Bennati, M., “Structural Examination of the Transient 3-Aminotyrosyl Radical on the PCET Pathway of E. coli Ribonucleotide Reductase by Multifrequency EPR Spectroscopy.” Journal of the American Chemical Society 2009, 131 (43), 15729-15738.
Offenbacher, A. R.; Vassiliev, I. R.; Seyedsayamdost, M. R.; Stubbe, J.; Barry, B. A., “Redox-Linked Structural Changes in Ribonucleotide Reductase.” Journal of the American Chemical Society 2009, 131 (22), 7496-+.
Minnihan, E. C.; Seyedsayamdost, M. R.; Stubbe, J., “Use of 3-Aminotyrosine To Examine the Pathway Dependence of Radical Propagation in Escherichia coli Ribonucleotide Reductase.” Biochemistry 2009, 48 (51), 12125-12132.
Reece, S. Y.; Lutterman, D. A.; Seyedsayamdost, M. R.; Stubbe, J.; Nocera, D. G., “Re(bpy)(CO)(3)CN as a Probe of Conformational Flexibility in a Photochemical Ribonucleotide Reductase.” Biochemistry 2009, 48 (25), 5832-5838.
Reece, S. Y.; Seyedsayamdost, M. R.; Stubbe, J.; Nocera, D. G., “Direct observation of a transient tyrosine radical competent for initiating turnover in a photochemical ribonucleotide reductase.” Journal of the American Chemical Society 2007, 129 (45), 13828-+.
Seyedsayamdost, M. R.; Chan, C. T. Y.; Mugnaini, V.; Stubbe, J.; Bennati, M., “PELDOR spectroscopy with DOPA-beta 2 and NH2Y-alpha 2s: Distance measurements between residues involved in the radical propagation pathway of E-coli ribonucleotide reductase.” Journal of the American Chemical Society 2007, 129 (51), 15748-+.
Seyedsayamdost, M. R.; Xie, J.; Chan, C. T. Y.; Schultz, P. G.; Stubbe, J., “Site-specific insertion of 3-aminotyrosine into subunit alpha 2 of E-coli ribonucleotide reductase: Direct evidence for involvement of Y-730 and Y-731 in radical propagation.” Journal of the American Chemical Society 2007, 129 (48), 15060-15071.
Reece, S. Y.; Seyedsayamdost, M. R.; Stubbe, J.; Nocera, D. G., “Photoactive peptides for light-initiated tyrosyl radical generation and transport into ribonucleotide reductase.” Journal of the American Chemical Society 2007, 129 (27), 8500-8509.
Seyedsayamdost, M. R.; Stubbe, J., “Forward and reverse electron transfer with the Y(356)DOPA-beta 2 heterodimer of E-coli ribonucleotide reductase.” Journal of the American Chemical Society 2007, 129 (8), 2226-+.
Seyedsayamdost, M. R.; Yee, C. S.; Stubbe, J., “Site-specific incorporation of fluorotyrosines into the R2 subunit of E-coli ribonucleotide reductase by expressed protein ligation.” Nature Protocols 2007, 2 (5), 1225-1235.
Reece, S. Y.; Seyedsayamdost, M. R.; Stubbe, J.; Nocera, D. G., “Electron transfer reactions of fluorotyrosyl radicals.” Journal of the American Chemical Society 2006, 128 (42), 13654-13655.
Seyedsayamdost, M. R.; Stubbe, J., “Site-specific replacement of Y-356 with 3,4-dihydroxyphenylalanine in the beta 2 subunit of E. coli ribonucleotide reductase.” Journal of the American Chemical Society 2006, 128 (8), 2522-2523.
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