Mohammad R Seyedsayamdost
Princeton University, NJ·Chemistry
Bacteria make a huge variety of small molecules, called natural products, that they use to fight rivals, signal to each other and interact with their hosts. Many medicines, including antibiotics and anticancer drugs, came from these molecules.
- Fields
Chemistry
Biochemistry
Microbiology & Immunology
- Topics
natural products
secondary metabolites
cryptic biosynthetic gene clusters
- Grants
- 5 known grants, through Mar 2031
What they work on
- Use high-throughput elicitor screening (HiTES) and genome-guided searches to uncover cryptic natural products in human microbiome bacteria, including radical SAM-modified peptides and selenium-containing metabolites.
- Identify secondary metabolites that three Corynebacterium strains use to fight each other, antagonize Staphylococcus aureus and change cytokine production by host cells, using HiTES.
- Discover new enediynes, potent DNA-cutting molecules, by combining HiTES with DNA cleavage assays, and develop synthetic strategies to stabilize nine-membered-ring enediynes such as clavulyne.
- Search for products of divergent bleomycin and mitomycin gene clusters, guided by bioinformatics, and use untargeted bioassays to find new classes of DNA-targeting anticancer compounds.
- Find a small-molecule inhibitor of methionine synthase and test whether it kills Burkholderia pseudomallei together with low-dose trimethoprim, a chemical synthetic lethal combination.
- Run forward chemical and genetic screens in Pseudomonas aeruginosa under low-dose antibiotics to discover new synthetic lethal drug combinations and antimicrobial targets.
- Determine how non-cysteine amino acid ligands change the heme electronic structure, oxygen activation and reactivity of non-canonical P450 enzymes, using spectroscopy, structures and guided mutagenesis.
- Uncover the biological roles and new oxidative reactions of ncCYPs by reconstructing their biosynthetic gene clusters and screening the enzymes against substrate libraries.
More about the research
Bacterial genomes show that most such molecules have never been seen, because the genes that make them are silent, or 'cryptic', under ordinary laboratory conditions. Across its projects, the lab uncovers these hidden molecules, works out the enzymes that build them, and uses that knowledge to find new antibiotics and anticancer agents.
Why it matters
New antibiotics are urgently needed against multidrug-resistant pathogens such as Pseudomonas aeruginosa and Burkholderia pseudomallei. New drug targets and effective drug combinations could help treat these infections. Newly discovered DNA-damaging molecules could become anticancer lead compounds or payloads for antibody-drug conjugates. Microbiome studies could inform therapies against Corynebacterium infections, and new P450 enzymes could become tools for greener chemical manufacturing.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Discovery and synthesis of cryptic enediynes and microbial cytotoxins
NIH · Apr 2026 – Mar 2031
From Genes to Molecules and Back: Expanding the Chemical Space of Microbial and Microbiome Natural Products
NIH · Sep 2024 – Aug 2029
Exploring the Biosynthetic Landscape and Reaction Mechanisms of Non-Canonical Cytochrome P450 Enzymes
NSF · Aug 2026 – Jul 2029
Closest labs
Reed Stubbendieck
Oklahoma State University, OK·Microbiology & Immunology
Culture Dolosigranulum pigrum from nasal swabs and test its inhibition of multiple Staphylococcus aureus strains with co-culture plate assays under conditions mimicking the human nose.
Nancy Keller
University of Wisconsin-Madison, WI·Microbiology & Immunology
Determine the chemical products of isocyanide synthase (ICS) gene clusters that carry unusual enzymes or target proteins, using molecular and chemical analysis of fungi found by the lab's genome-mining pipeline.
Katharine Watts
California Polytechnic State University-San Luis Obispo, CA·Biochemistry
Identify the role of individual genes in TLN-05220 biosynthesis by making gene knockouts in the wild-type bacterium that naturally produces this Echinosporamicin-type antibiotic.
The school
Princeton University: 26 labs on PI Pages, $559M a year on research, 403 research doctorates a year.
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