Seyedsayamdost Lab
Principal Investigator: Mohammad R Seyedsayamdost
Institution: Princeton University (Princeton, NJ)
Primary Subfield: Molecular & Cell Bio
Recruitment Status: Inquire for rotation/fellowship opportunities
Research Focus
Project Summary & Abstract Microbial natural products have yielded remarkable anticancer agents, such as enediyne antibiotics, bleomycin, and mitomycin, that directly target DNA and induce double-strand breaks or DNA alkylation. The recent surge in microbial genome sequencing has uncovered the genetic fingerprints for thousands of molecules within these categories. However, only a tiny fraction of this potential has been harnessed, as the discovery process is hindered by the transcriptionally silent nature of the corresponding biosynthetic genes and the extremely low production levels, even when these genes are expressed. We have established methods to access metabolites encoded by transcriptionally silent or ‘cryptic’ biosynthetic gene clusters. Using a forward chemical genetics approach, termed high-throughput elicitor screening (HiTES), we have identified >150 novel, cryptic metabolites. Very recently, we have utilized the approach in conjunction with DNA cleavage assays to identify a new, cryptic enediyne that we have named clavulyne. We are therefore poised to apply this method broadly in the current proposal to discover novel enediyne natural products, thereby expanding the c…
Active NIH Awards
- 1R01CA300566-01A1: Discovery and synthesis of cryptic enediynes and microbial cytotoxins (2026)
- 5R35GM152049-03: From Genes to Molecules and Back: Expanding the Chemical Space of Microbial and Microbiome Natural Products (2026)
- 5R35GM152049-02: From Genes to Molecules and Back: Expanding the Chemical Space of Microbial and Microbiome Natural Products (2025)
- 1R21AI190827-01: Using Chemical Synthetic Lethality to Identify New Antimicrobial Targets in Gram-Negative Bacterial Pathogens (2025)
- 1R21AT013123-01: Talking with Small Molecules: Corynebacteria in the Human Microbiome (2024)
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