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.
-
Momomycin, an Antiproliferative Cryptic Metabolite from the Oxytetracycline Producer Streptomyces rimosus. Angew Chem Int Ed Engl. 2022 ;61(39):e202208573. .
-
The Small-Molecule Language of Dynamic Microbial Interactions. Annu Rev Microbiol. 2022 ;76:641-660. .
-
Bioinformatic Atlas of Radical SAM Enzyme-Modified RiPP Natural Products Reveals an Isoleucine-Tryptophan Crosslink. J Am Chem Soc. 2022 ;144(39):17876-17888. .
-
Bicyclostreptins are radical SAM enzyme-modified peptides with unique cyclization motifs. Nat Chem Biol. 2022 ;18(10):1135-1143. .
-
Biosynthesis of selenium-containing small molecules in diverse microorganisms. Nature. 2022 ;610(7930):199-204. .
-
Targeted Discovery of Cryptic Metabolites with Antiproliferative Activity. ACS Chem Biol. 2022 ;17(11):3121-3130. .
-
Induction of Diverse Cryptic Fungal Metabolites by Steroids and Channel Blockers. Angew Chem Int Ed Engl. 2022 ;61(29):e202204519. .
-
Structural Elucidation of Cryptic Algaecides in Marine Algal-Bacterial Symbioses by NMR Spectroscopy and MicroED. Angew Chem Int Ed Engl. 2022 ;61(4):e202114022. .
-
Biosynthesis-guided discovery reveals enteropeptins as alternative sactipeptides containing N-methylornithine. Nat Chem. 2022 ;14(12):1390-1398. .
-
Vitamin B3 Triggers Biosynthesis of Secondary Metabolite Dormancy Signals in . J Am Chem Soc. 2022 ;144(33):14997-15001. .
-
RaS-RiPPs in Streptococci and the Human Microbiome. ACS Bio Med Chem Au. 2022 ;2(4):328-339. .
-
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. .
-
Structural insights into inhibition of the drug target dihydroorotate dehydrogenase by bacterial hydroxyalkylquinolines. RSC Chem Biol. 2022 ;3(4):420-425. .
-
Guidelines for metabolomics-guided transposon mutagenesis for microbial natural product discovery. Methods Enzymol. 2022 ;665:305-323. .
-
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). .
-
Piperacillin triggers virulence factor biosynthesis via the oxidative stress response in . Proc Natl Acad Sci U S A. 2021 ;118(26). .
-
A Natural Product Chemist's Guide to Unlocking Silent Biosynthetic Gene Clusters. Annu Rev Biochem. 2021 ;90:763-788. .
-
MetEx, a Metabolomics Explorer Application for Natural Product Discovery. ACS Chem Biol. 2021 ;16(12):2825-2833. .
-
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. .
-
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. .
-
Unlocking Cryptic Metabolites with Mass Spectrometry-Guided Transposon Mutant Selection. ACS Chem Biol. 2020 ;15(10):2766-2774. .
-
Secondary metabolites from the Burkholderia pseudomallei complex: structure, ecology, and evolution. J Ind Microbiol Biotechnol. 2020 ;47(9-10):877-887. .
-
Thailandenes, Cryptic Polyene Natural Products Isolated from Using Phenotype-Guided Transposon Mutagenesis. ACS Chem Biol. 2020 ;15(5):1195-1203. .
-
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. .
-
Special Issue in Honor of Professor Jon Clardy. J Nat Prod. 2020 ;83(3):565-568. .
-
Reporter-Guided Transposon Mutant Selection for Activation of Silent Gene Clusters in Burkholderia thailandensis. Chembiochem. 2020 ;21(13):1826-1831. .
-
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. .
-
A microbial metabolite synergizes with endogenous serotonin to trigger reproductive behavior. Proc Natl Acad Sci U S A. 2020 ;117(48):30589-30598. .
-
Mapping and Exploiting the Promiscuity of OxyB toward the Biocatalytic Production of Vancomycin Aglycone Variants. ACS Catal. 2020 ;10(16):9287-9298. .
-
CanE, an Iron/2-Oxoglutarate-Dependent Lasso Peptide Hydroxylase from . ACS Chem Biol. 2020 ;15(4):890-894. .
-
Total Synthesis and Stereochemical Assignment of Streptide. J Am Chem Soc. 2019 ;141(43):17361-17369. .
-
Macrocyclization via an Arginine-Tyrosine Crosslink Broadens the Reaction Scope of Radical -Adenosylmethionine Enzymes. J Am Chem Soc. 2019 ;141(42):16610-16614. .
-
Toward a global picture of bacterial secondary metabolism. J Ind Microbiol Biotechnol. 2019 ;46(3-4):301-311. .
-
Aliphatic Ether Bond Formation Expands the Scope of Radical SAM Enzymes in Natural Product Biosynthesis. J Am Chem Soc. 2019 ;141(27):10610-10615. .
-
Radical Approach to Enzymatic β-Thioether Bond Formation. J Am Chem Soc. 2019 ;141(2):990-997. .
-
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. .
-
A genetics-free method for high-throughput discovery of cryptic microbial metabolites. Nat Chem Biol. 2019 ;15(2):161-168. .
-
Identification of the Hypertension Drug Guanfacine as an Antivirulence Agent in Pseudomonas aeruginosa. Chembiochem. 2019 ;20(15):2005-2011. .
-
Cebulantin, a Cryptic Lanthipeptide Antibiotic Uncovered Using Bioactivity-Coupled HiTES. Angew Chem Int Ed Engl. 2019 ;58(18):5973-5977. .
-
Bioactivity-HiTES Unveils Cryptic Antibiotics Encoded in Actinomycete Bacteria. ACS Chem Biol. 2019 ;14(4):767-774. .
-
Multiple siderophores: bug or feature?. J Biol Inorg Chem. 2018 ;23(7):983-993. .
-
Recent advances in activating silent biosynthetic gene clusters in bacteria. Curr Opin Microbiol. 2018 ;45:156-163. .
-
Installation of Multiple Aryl Ether Crosslinks onto Non-Native Substrate Peptides by the Vancomycin OxyB. Tetrahedron. 2018 ;74(26):3231-3237. .
-
The Polyene Natural Product Thailandamide A Inhibits Fatty Acid Biosynthesis in Gram-Positive and Gram-Negative Bacteria. Biochemistry. 2018 ;57(29):4247-4251. .
-
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. .
-
Malleilactone Is a Burkholderia pseudomallei Virulence Factor Regulated by Antibiotics and Quorum Sensing. J Bacteriol. 2018 ;200(14). .
-
Modulating OxyB-Catalyzed Cross-Coupling Reactions in Vancomycin Biosynthesis by Incorporation of Diverse d-Tyr Analogues. J Org Chem. 2018 ;83(13):7309-7317. .
-
In Vitro Reconstitution of OxyC Activity Enables Total Chemoenzymatic Syntheses of Vancomycin Aglycone Variants. Angew Chem Int Ed Engl. 2018 ;57(27):8048-8052. .
-
Mechanistic Investigations of Lysine-Tryptophan Cross-Link Formation Catalyzed by Streptococcal Radical S-Adenosylmethionine Enzymes. Biochemistry. 2018 ;57(4):461-468. .
-
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. .
-
Charting an Unexplored Streptococcal Biosynthetic Landscape Reveals a Unique Peptide Cyclization Motif. J Am Chem Soc. 2018 ;140(50):17674-17684. .
-
Small Biomolecules for Big Applications. ACS Cent Sci. 2018 ;4(4):437-439. .
-
Guidelines for Determining the Structures of Radical SAM Enzyme-Catalyzed Modifications in the Biosynthesis of RiPP Natural Products. Methods Enzymol. 2018 ;606:439-460. .
-
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. .
-
Though Much Is Taken, Much Abides: Finding New Antibiotics Using Old Ones. Biochemistry. 2017 ;56(37):4925-4926. .
-
In Vitro Reconstitution of OxyA Enzymatic Activity Clarifies Late Steps in Vancomycin Biosynthesis. ACS Chem Biol. 2017 ;12(9):2248-2253. .
-
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. .
-
Long-range proton-coupled electron transfer in the class Ia ribonucleotide reductase. Essays Biochem. 2017 ;61(2):281-292. .
-
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. .
-
Discovery of a Cryptic Antifungal Compound from Streptomyces albus J1074 Using High-Throughput Elicitor Screens. J Am Chem Soc. 2017 ;139(27):9203-9212. .
-
Antibiotic dialogues: induction of silent biosynthetic gene clusters by exogenous small molecules. FEMS Microbiol Rev. 2017 ;41(1):19-33. .
-
Synergy and Target Promiscuity Drive Structural Divergence in Bacterial Alkylquinolone Biosynthesis. Cell Chem Biol. 2017 ;24(12):1437-1444.e3. .
-
Lysine-Tryptophan-Crosslinked Peptides Produced by Radical SAM Enzymes in Pathogenic Streptococci. ACS Chem Biol. 2017 ;12(4):922-927. .
-
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. .
-
sp. ATCC 55076 harbours the largest actinomycete chromosome to date and the kistamicin biosynthetic gene cluster. Medchemcomm. 2017 ;8(4):780-788. .
-
The Siderophore Metabolome of Azotobacter vinelandii. Appl Environ Microbiol. 2016 ;82(1):27-39. .
-
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. .
-
Mapping the Trimethoprim-Induced Secondary Metabolome of Burkholderia thailandensis. ACS Chem Biol. 2016 ;11(8):2124-30. .
-
A Burkholderia thailandensis Acyl-Homoserine Lactone-Independent Orphan LuxR Homolog That Activates Production of the Cytotoxin Malleilactone. J Bacteriol. 2015 ;197(21):3456-62. .
-
Structure and biosynthesis of a macrocyclic peptide containing an unprecedented lysine-to-tryptophan crosslink. Nat Chem. 2015 ;7(5):431-437. .
-
Hybrid biosynthesis of roseobacticides from algal and bacterial precursor molecules. J Am Chem Soc. 2014 ;136(43):15150-3. .
-
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. .
-
Mixing and matching siderophore clusters: structure and biosynthesis of serratiochelins from Serratia sp. V4. J Am Chem Soc. 2012 ;134(33):13550-3. .
-
Structure and biosynthesis of amychelin, an unusual mixed-ligand siderophore from Amycolatopsis sp. AA4. J Am Chem Soc. 2011 ;133(30):11434-7. .
-
The Jekyll-and-Hyde chemistry of Phaeobacter gallaeciensis. Nat Chem. 2011 ;3(4):331-5. .
-
Quorum-sensing-regulated bactobolin production by Burkholderia thailandensis E264. Org Lett. 2010 ;12(4):716-9. .
-
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. .