Associated Faculty, Chemistry

Contact

mrseyed@princeton.edu
609-258-5941
Frick Chemistry Laboratory, 333

Research Area

Microbiology & Virology

Research Focus

Discovery of new small molecules and biosynthetic pathways involved in microbial symbiotic interactions; elucidation of enzyme-catalyzed reaction mechanisms



Research
Selected Publications
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. ?




Kayrouz CM, Huang J, Hauser N, Seyedsayamdost MR. Biosynthesis of selenium-containing small molecules in diverse microorganisms. Nature. 2022 ;. PubMed
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Clark KA, Bushin LB, Seyedsayamdost MR. RaS-RiPPs in Streptococci and the Human Microbiome. ACS Bio Med Chem Au. 2022 ;2(4):328-339. PubMed
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Bushin LB, Covington BC, Clark KA, Caruso A, Seyedsayamdost MR. Bicyclostreptins are radical SAM enzyme-modified peptides with unique cyclization motifs. Nat Chem Biol. 2022 ;. PubMed
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Horwitz SM, Blue TC, Ambarian JA, Hoshino S, Seyedsayamdost MR, Davis KM. Structural insights into inhibition of the drug target dihydroorotate dehydrogenase by bacterial hydroxyalkylquinolines. RSC Chem Biol. 2022 ;3(4):420-425. PubMed
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Li Y, Lee SRak, Han EJ, Seyedsayamdost MR. Momomycin, an Antiproliferative Cryptic Metabolite from the Oxytetracycline Producer Streptomyces rimosus. Angew Chem Int Ed Engl. 2022 ;61(39):e202208573. PubMed
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Zhang Y, Gallant é, Park J-D, Seyedsayamdost MR. The Small-Molecule Language of Dynamic Microbial Interactions. Annu Rev Microbiol. 2022 ;76:641-660. PubMed
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Covington BC, Seyedsayamdost MR. Vitamin B3 Triggers Biosynthesis of Secondary Metabolite Dormancy Signals in . J Am Chem Soc. 2022 ;144(33):14997-15001. PubMed
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Lee SRak, Seyedsayamdost MR. Induction of Diverse Cryptic Fungal Metabolites by Steroids and Channel Blockers. Angew Chem Int Ed Engl. 2022 ;61(29):e202204519. PubMed
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Wang R, Gallant é, Wilson MZ, Wu Y, Li A, Gitai Z, et al.. Algal p-coumaric acid induces oxidative stress and siderophore biosynthesis in the bacterial symbiont Phaeobacter inhibens. Cell Chem Biol. 2022 ;29(4):670-679.e5. PubMed
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Park J-D, Li Y, Moon K, Han EJ, Lee SRak, Seyedsayamdost MR. Structural Elucidation of Cryptic Algaecides in Marine Algal-Bacterial Symbioses by NMR Spectroscopy and MicroED. Angew Chem Int Ed Engl. 2022 ;61(4):e202114022. PubMed
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Covington BC, Seyedsayamdost MR. Guidelines for metabolomics-guided transposon mutagenesis for microbial natural product discovery. Methods Enzymol. 2022 ;665:305-323. PubMed
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Rued BE, Covington BC, Bushin LB, Szewczyk G, Laczkovich I, Seyedsayamdost MR, et al. Erratum for Rued et al., "Quorum Sensing in Streptococcus mutans Regulates Production of Tryglysin, a Novel RaS-RiPP Antimicrobial Compound". mBio. 2021 ;12(5):e0256021. PubMed
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Covington BC, Seyedsayamdost MR. MetEx, a Metabolomics Explorer Application for Natural Product Discovery. ACS Chem Biol. 2021 ;16(12):2825-2833. PubMed
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Caruso A, Seyedsayamdost MR. Radical SAM Enzyme QmpB Installs Two 9-Membered Ring Sactionine Macrocycles during Biogenesis of a Ribosomal Peptide Natural Product. J Org Chem. 2021 ;86(16):11284-11289. PubMed
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Li A, Okada BK, Rosen PC, Seyedsayamdost MR. Piperacillin triggers virulence factor biosynthesis via the oxidative stress response in . Proc Natl Acad Sci U S A. 2021 ;118(26). PubMed
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Covington BC, Xu F, Seyedsayamdost MR. A Natural Product Chemist's Guide to Unlocking Silent Biosynthetic Gene Clusters. Annu Rev Biochem. 2021 ;90:763-788. PubMed
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Balo AR, Caruso A, Tao L, Tantillo DJ, Seyedsayamdost MR, R Britt D. Trapping a cross-linked lysine-tryptophan radical in the catalytic cycle of the radical SAM enzyme SuiB. Proc Natl Acad Sci U S A. 2021 ;118(21). PubMed
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Rued BE, Covington BC, Bushin LB, Szewczyk G, Laczkovich I, Seyedsayamdost MR, et al. Quorum Sensing in Streptococcus mutans Regulates Production of Tryglysin, a Novel RaS-RiPP Antimicrobial Compound. mBio. 2021 ;12(2). PubMed
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Forneris CC, Nguy AKL, Seyedsayamdost MR. Mapping and Exploiting the Promiscuity of OxyB toward the Biocatalytic Production of Vancomycin Aglycone Variants. ACS Catal. 2020 ;10(16):9287-9298. PubMed
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Klaus JR, Coulon PML, Koirala P, Seyedsayamdost MR, Déziel E, Chandler JR. Secondary metabolites from the Burkholderia pseudomallei complex: structure, ecology, and evolution. J Ind Microbiol Biotechnol. 2020 ;47(9-10):877-887. PubMed
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Zhang C, Seyedsayamdost MR. Discovery of a Cryptic Depsipeptide from Streptomyces ghanaensis via MALDI-MS-Guided High-Throughput Elicitor Screening. Angew Chem Int Ed Engl. 2020 ;59(51):23005-23009. PubMed
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Chen Y-C, Seyedsayamdost MR, Ringstad N. A microbial metabolite synergizes with endogenous serotonin to trigger reproductive behavior. Proc Natl Acad Sci U S A. 2020 ;117(48):30589-30598. PubMed
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Yoshimura A, Covington BC, Gallant é, Zhang C, Li A, Seyedsayamdost MR. Unlocking Cryptic Metabolites with Mass Spectrometry-Guided Transposon Mutant Selection. ACS Chem Biol. 2020 ;15(10):2766-2774. PubMed
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Bushin LB, Covington BC, Rued BE, Federle MJ, Seyedsayamdost MR. 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(38):16265-16275. PubMed
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Mao D, Yoshimura A, Wang R, Seyedsayamdost MR. Reporter-Guided Transposon Mutant Selection for Activation of Silent Gene Clusters in Burkholderia thailandensis. Chembiochem. 2020 ;21(13):1826-1831. PubMed
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Park J-D, Moon K, Miller C, Rose J, Xu F, Ebmeier CC, et al. Thailandenes, Cryptic Polyene Natural Products Isolated from Using Phenotype-Guided Transposon Mutagenesis. ACS Chem Biol. 2020 ;15(5):1195-1203. PubMed
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Zhang C, Seyedsayamdost MR. CanE, an Iron/2-Oxoglutarate-Dependent Lasso Peptide Hydroxylase from . ACS Chem Biol. 2020 ;15(4):890-894. PubMed
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E Greenberg P, Chandler JR, Seyedsayamdost MR. The Chemistry and Biology of Bactobolin: A 10-Year Collaboration with Natural Product Chemist Extraordinaire Jon Clardy. J Nat Prod. 2020 ;83(3):738-743. PubMed
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Seyedsayamdost MR, Stallforth P. Special Issue in Honor of Professor Jon Clardy. J Nat Prod. 2020 ;83(3):565-568. PubMed
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Li A, Mao D, Yoshimura A, Rosen PC, W Martin L, Gallant é, et al.. Multi-Omic Analyses Provide Links between Low-Dose Antibiotic Treatment and Induction of Secondary Metabolism in Burkholderia thailandensis. mBio. 2020 ;11(1). PubMed
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Seyedsayamdost MR. Toward a global picture of bacterial secondary metabolism. J Ind Microbiol Biotechnol. 2019 ;46(3-4):301-311. PubMed
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Isley NA, Endo Y, Wu Z-C, Covington BC, Bushin LB, Seyedsayamdost MR, et al. Total Synthesis and Stereochemical Assignment of Streptide. J Am Chem Soc. 2019 ;141(43):17361-17369. PubMed
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Caruso A, Martinie RJ, Bushin LB, Seyedsayamdost MR. Macrocyclization via an Arginine-Tyrosine Crosslink Broadens the Reaction Scope of Radical -Adenosylmethionine Enzymes. J Am Chem Soc. 2019 ;141(42):16610-16614. PubMed
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Okada BK, Li A, Seyedsayamdost MR. Identification of the Hypertension Drug Guanfacine as an Antivirulence Agent in Pseudomonas aeruginosa. Chembiochem. 2019 ;20(15):2005-2011. PubMed
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Clark KA, Bushin LB, Seyedsayamdost MR. Aliphatic Ether Bond Formation Expands the Scope of Radical SAM Enzymes in Natural Product Biosynthesis. J Am Chem Soc. 2019 ;141(27):10610-10615. PubMed
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Moon K, Xu F, Seyedsayamdost MR. Cebulantin, a Cryptic Lanthipeptide Antibiotic Uncovered Using Bioactivity-Coupled HiTES. Angew Chem Int Ed Engl. 2019 ;58(18):5973-5977. PubMed
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Moon K, Xu F, Zhang C, Seyedsayamdost MR. Bioactivity-HiTES Unveils Cryptic Antibiotics Encoded in Actinomycete Bacteria. ACS Chem Biol. 2019 ;14(4):767-774. PubMed
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Stubbe JA, Seyedsayamdost MR. Discovery of a New Class I Ribonucleotide Reductase with an Essential DOPA Radical and NO Metal as an Initiator of Long-Range Radical Transfer. Biochemistry. 2019 ;58(6):435-437. PubMed
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Xu F, Wu Y, Zhang C, Davis KM, Moon K, Bushin LB, et al. A genetics-free method for high-throughput discovery of cryptic microbial metabolites. Nat Chem Biol. 2019 ;15(2):161-168. PubMed
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Caruso A, Bushin LB, Clark KA, Martinie RJ, Seyedsayamdost MR. Radical Approach to Enzymatic β-Thioether Bond Formation. J Am Chem Soc. 2019 ;141(2):990-997. PubMed
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Forneris CC, Ozturk S, Sorensen EJ, Seyedsayamdost MR. Installation of Multiple Aryl Ether Crosslinks onto Non-Native Substrate Peptides by the Vancomycin OxyB. Tetrahedron. 2018 ;74(26):3231-3237. PubMed
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Gibson MI, Seyedsayamdost MR. Small Biomolecules for Big Applications. ACS Cent Sci. 2018 ;4(4):437-439. PubMed
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Bushin LB, Clark KA, Pelczer I, Seyedsayamdost MR. Charting an Unexplored Streptococcal Biosynthetic Landscape Reveals a Unique Peptide Cyclization Motif. J Am Chem Soc. 2018 ;140(50):17674-17684. PubMed
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Mao D, Okada BK, Wu Y, Xu F, Seyedsayamdost MR. Recent advances in activating silent biosynthetic gene clusters in bacteria. Curr Opin Microbiol. 2018 ;45:156-163. PubMed
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McRose DL, Seyedsayamdost MR, Morel FMM. Multiple siderophores: bug or feature?. J Biol Inorg Chem. 2018 ;23(7):983-993. PubMed
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Wu Y, Seyedsayamdost MR. The Polyene Natural Product Thailandamide A Inhibits Fatty Acid Biosynthesis in Gram-Positive and Gram-Negative Bacteria. Biochemistry. 2018 ;57(29):4247-4251. PubMed
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McRose DL, Baars O, Seyedsayamdost MR, Morel FMM. 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. PubMed
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Klaus JR, Deay J, Neuenswander B, Hursh W, Gao Z, Bouddhara T, et al. Malleilactone Is a Burkholderia pseudomallei Virulence Factor Regulated by Antibiotics and Quorum Sensing. J Bacteriol. 2018 ;200(14). PubMed
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Ozturk S, Forneris CC, Nguy AKL, Sorensen EJ, Seyedsayamdost MR. Modulating OxyB-Catalyzed Cross-Coupling Reactions in Vancomycin Biosynthesis by Incorporation of Diverse d-Tyr Analogues. J Org Chem. 2018 ;83(13):7309-7317. PubMed
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Forneris CC, Seyedsayamdost MR. In Vitro Reconstitution of OxyC Activity Enables Total Chemoenzymatic Syntheses of Vancomycin Aglycone Variants. Angew Chem Int Ed Engl. 2018 ;57(27):8048-8052. PubMed
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Schramma KR, Forneris CC, Caruso A, Seyedsayamdost MR. Mechanistic Investigations of Lysine-Tryptophan Cross-Link Formation Catalyzed by Streptococcal Radical S-Adenosylmethionine Enzymes. Biochemistry. 2018 ;57(4):461-468. PubMed
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Baars O, Zhang X, Gibson MI, Stone AT, Morel FMM, Seyedsayamdost MR. 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. PubMed
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Bushin LB, Seyedsayamdost MR. Guidelines for Determining the Structures of Radical SAM Enzyme-Catalyzed Modifications in the Biosynthesis of RiPP Natural Products. Methods Enzymol. 2018 ;606:439-460. PubMed
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Nazari B, Forneris CC, Gibson MI, Moon K, Schramma KR, Seyedsayamdost MR. sp. ATCC 55076 harbours the largest actinomycete chromosome to date and the kistamicin biosynthetic gene cluster. Medchemcomm. 2017 ;8(4):780-788. PubMed
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Wu Y, Seyedsayamdost MR. Synergy and Target Promiscuity Drive Structural Divergence in Bacterial Alkylquinolone Biosynthesis. Cell Chem Biol. 2017 ;24(12):1437-1444.e3. PubMed
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Wang R, Seyedsayamdost MR. 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. PubMed
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Davis KM, Schramma KR, Hansen WA, Bacik JP, Khare SD, Seyedsayamdost MR, et al. 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. PubMed
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Rosen PC, Seyedsayamdost MR. Though Much Is Taken, Much Abides: Finding New Antibiotics Using Old Ones. Biochemistry. 2017 ;56(37):4925-4926. PubMed
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Forneris CC, Ozturk S, Gibson MI, Sorensen EJ, Seyedsayamdost MR. In Vitro Reconstitution of OxyA Enzymatic Activity Clarifies Late Steps in Vancomycin Biosynthesis. ACS Chem Biol. 2017 ;12(9):2248-2253. PubMed
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Xu F, Nazari B, Moon K, Bushin LB, Seyedsayamdost MR. Discovery of a Cryptic Antifungal Compound from Streptomyces albus J1074 Using High-Throughput Elicitor Screens. J Am Chem Soc. 2017 ;139(27):9203-9212. PubMed
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Reece SY, Seyedsayamdost MR. Long-range proton-coupled electron transfer in the class Ia ribonucleotide reductase. Essays Biochem. 2017 ;61(2):281-292. PubMed
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Schramma KR, Seyedsayamdost MR. Lysine-Tryptophan-Crosslinked Peptides Produced by Radical SAM Enzymes in Pathogenic Streptococci. ACS Chem Biol. 2017 ;12(4):922-927. PubMed
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Mao D, Bushin LB, Moon K, Wu Y, Seyedsayamdost MR. Discovery of as a global regulator of secondary metabolism and virulence in E264. Proc Natl Acad Sci U S A. 2017 ;114(14):E2920-E2928. PubMed
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Metelev M, Arseniev, ii A, Bushin LB, Kuznedelov K, Artamonova TO, Kondratenko R, et al. 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. PubMed
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Okada BK, Seyedsayamdost MR. Antibiotic dialogues: induction of silent biosynthetic gene clusters by exogenous small molecules. FEMS Microbiol Rev. 2017 ;41(1):19-33. PubMed
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Wang R, Gallant é, Seyedsayamdost MR. Investigation of the Genetics and Biochemistry of Roseobacticide Production in the Roseobacter Clade Bacterium Phaeobacter inhibens. mBio. 2016 ;7(2):e02118. PubMed
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Wilson MZ, Wang R, Gitai Z, Seyedsayamdost MR. 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. PubMed
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Okada BK, Wu Y, Mao D, Bushin LB, Seyedsayamdost MR. Mapping the Trimethoprim-Induced Secondary Metabolome of Burkholderia thailandensis. ACS Chem Biol. 2016 ;11(8):2124-30. PubMed
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Baars O, Zhang X, Morel FMM, Seyedsayamdost MR. The Siderophore Metabolome of Azotobacter vinelandii. Appl Environ Microbiol. 2016 ;82(1):27-39. PubMed
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Truong TT, Seyedsayamdost M, E Greenberg P, Chandler JR. A Burkholderia thailandensis Acyl-Homoserine Lactone-Independent Orphan LuxR Homolog That Activates Production of the Cytotoxin Malleilactone. J Bacteriol. 2015 ;197(21):3456-62. PubMed
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Schramma KR, Bushin LB, Seyedsayamdost MR. Structure and biosynthesis of a macrocyclic peptide containing an unprecedented lysine-to-tryptophan crosslink. Nat Chem. 2015 ;7(5):431-437. PubMed
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Seyedsayamdost MR, Wang R, Kolter R, Clardy J. Hybrid biosynthesis of roseobacticides from algal and bacterial precursor molecules. J Am Chem Soc. 2014 ;136(43):15150-3. PubMed
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Seyedsayamdost MR. 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. PubMed
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Seyedsayamdost MR, Cleto S, Carr G, Vlamakis H, Vieira MJo?o, Kolter R, et al.. Mixing and matching siderophore clusters: structure and biosynthesis of serratiochelins from Serratia sp. V4. J Am Chem Soc. 2012 ;134(33):13550-3. PubMed
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Seyedsayamdost MR, Traxler MF, Zheng S-L, Kolter R, Clardy J. Structure and biosynthesis of amychelin, an unusual mixed-ligand siderophore from Amycolatopsis sp. AA4. J Am Chem Soc. 2011 ;133(30):11434-7. PubMed
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Seyedsayamdost MR, Case RJ, Kolter R, Clardy J. The Jekyll-and-Hyde chemistry of Phaeobacter gallaeciensis. Nat Chem. 2011 ;3(4):331-5. PubMed
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Seyedsayamdost MR, Chandler JR, Blodgett JAV, Lima PS, Duerkop BA, Oinuma K-I, et al. Quorum-sensing-regulated bactobolin production by Burkholderia thailandensis E264. Org Lett. 2010 ;12(4):716-9. PubMed
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Seyedsayamdost MR, Argirevi? T, Minnihan EC, Stubbe JA, Bennati M. 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. PubMed
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Seyedsayamdost MR, Xie J, T Y Chan C, Schultz PG, Stubbe JA. Site-specific insertion of 3-aminotyrosine into subunit alpha2 of E. coli ribonucleotide reductase: direct evidence for involvement of Y730 and Y731 in radical propagation. J Am Chem Soc. 2007 ;129(48):15060-71. PubMed
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