Mohammad R. Seyedsayamdost
Associated Faculty, Chemistry
Contact
mrseyed@princeton.edu 609-258-5941
Frick Chemistry Laboratory, 333
Research Area
Microbiology & VirologyResearch Focus
Discovery of new small molecules and biosynthetic pathways involved in microbial symbiotic interactions; elucidation of enzyme-catalyzed reaction mechanismsMuch 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.
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. Malleilactone is a virulence factor regulated by antibiotics and quorum sensing. J Bacteriol. 2018 ;.
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. Recent advances in activating silent biosynthetic gene clusters in bacteria. Curr Opin Microbiol. 2018 ;45:156-163.
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. The Polyene Natural Product Thailandamide A Inhibits Fatty Acid Biosynthesis in Gram-Positive and Gram-Negative Bacteria. Biochemistry. 2018 ;57(29):4247-4251.
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. Quorum sensing and iron regulate a two-for-one siderophore gene cluster in . Proc Natl Acad Sci U S A. 2018 ;115(29):7581-7586.
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. Mechanistic Investigations of Lysine-Tryptophan Cross-Link Formation Catalyzed by Streptococcal Radical S-Adenosylmethionine Enzymes. Biochemistry. 2018 ;57(4):461-468.
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. Crochelins: Siderophores with an Unprecedented Iron-Chelating Moiety from the Nitrogen-Fixing Bacterium Azotobacter chroococcum. Angew Chem Int Ed Engl. 2018 ;57(2):536-541.
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. Structures of the peptide-modifying radical SAM enzyme SuiB elucidate the basis of substrate recognition. Proc Natl Acad Sci U S A. 2017 ;114(39):10420-10425.
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. Roseochelin B, an Algaecidal Natural Product Synthesized by the Roseobacter Phaeobacter inhibens in Response to Algal Sinapic Acid. Org Lett. 2017 ;19(19):5138-5141.
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. Discovery of a Cryptic Antifungal Compound from Streptomyces albus J1074 Using High-Throughput Elicitor Screens. J Am Chem Soc. 2017 ;139(27):9203-9212.
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. Synergy and Target Promiscuity Drive Structural Divergence in Bacterial Alkylquinolone Biosynthesis. Cell Chem Biol. 2017 ;24(12):1437-1444.e3.
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. Discovery ofas a global regulator of secondary metabolism and virulence inE264. Proc Natl Acad Sci U S A. 2017 ;114(14):E2920-E2928.
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. sp. ATCC 55076 harbours the largest actinomycete chromosome to date and the kistamicin biosynthetic gene cluster. Medchemcomm. 2017 ;8(4):780-788.
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. Though Much Is Taken, Much Abides: Finding New Antibiotics Using Old Ones. Biochemistry. 2017 ;56(37):4925-4926.
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. In Vitro Reconstitution of OxyA Enzymatic Activity Clarifies Late Steps in Vancomycin Biosynthesis. ACS Chem Biol. 2017 ;12(9):2248-2253.
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. Long-range proton-coupled electron transfer in theclass Ia ribonucleotide reductase. Essays Biochem. 2017 ;61(2):281-292.
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. Lysine-Tryptophan-Crosslinked Peptides Produced by Radical SAM Enzymes in Pathogenic Streptococci. ACS Chem Biol. 2017 ;12(4):922-927.
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. Acinetodin and Klebsidin, RNA Polymerase Targeting Lasso Peptides Produced by Human Isolates of Acinetobacter gyllenbergii and Klebsiella pneumoniae. ACS Chem Biol. 2017 ;12(3):814-824.
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. Antibiotic dialogues: induction of silent biosynthetic gene clusters by exogenous small molecules. FEMS Microbiol Rev. 2017 ;41(1):19-33.
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. Mode of action and resistance studies unveil new roles for tropodithietic acid as an anticancer agent and the γ-glutamyl cycle as a proton sink. Proc Natl Acad Sci U S A. 2016 ;113(6):1630-5.
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. Mapping the Trimethoprim-Induced Secondary Metabolome of Burkholderia thailandensis. ACS Chem Biol. 2016 ;11(8):2124-30.
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. The Siderophore Metabolome of Azotobacter vinelandii. Appl Environ Microbiol. 2016 ;82(1):27-39.
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. A Burkholderia thailandensis Acyl-Homoserine Lactone-Independent Orphan LuxR Homolog That Activates Production of the Cytotoxin Malleilactone. J Bacteriol. 2015 ;197(21):3456-62.
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. Structure and biosynthesis of a macrocyclic peptide containing an unprecedented lysine-to-tryptophan crosslink. Nat Chem. 2015 ;7(5):431-437.
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. Hybrid biosynthesis of roseobacticides from algal and bacterial precursor molecules. J Am Chem Soc. 2014 ;136(43):15150-3.
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. High-throughput platform for the discovery of elicitors of silent bacterial gene clusters. Proc Natl Acad Sci U S A. 2014 ;111(20):7266-71.
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. Mixing and matching siderophore clusters: structure and biosynthesis of serratiochelins from Serratia sp. V4. J Am Chem Soc. 2012 ;134(33):13550-3.
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. Structure and biosynthesis of amychelin, an unusual mixed-ligand siderophore from Amycolatopsis sp. AA4. J Am Chem Soc. 2011 ;133(30):11434-7.
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. The Jekyll-and-Hyde chemistry of Phaeobacter gallaeciensis. Nat Chem. 2011 ;3(4):331-5.
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. Quorum-sensing-regulated bactobolin production by Burkholderia thailandensis E264. Org Lett. 2010 ;12(4):716-9.
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. Structural examination of the transient 3-aminotyrosyl radical on the PCET pathway of E. coli ribonucleotide reductase by multifrequency EPR spectroscopy. J Am Chem Soc. 2009 ;131(43):15729-38.