Microbial natural products serve as a dominant source of pharmaceutical agents and comprise some of our most celebrated cures. Recent studies, however, have been plagued by the frequent rediscovery of old molecules. One underlying reason is that most natural product biosynthetic genes in a given bacterium are not significantly expressed under standard laboratory growth conditions. These so-called ‘silent’ or ‘cryptic’ gene clusters represent a large reservoir of bioactive metabolites and methods that unlock them would have a profound impact on natural product research and thereby on drug discovery. In this talk, I will present new strategies that my group has developed for activating silent biosynthetic gene clusters and uncovering novel 'hidden' natural products with activities that, in some cases, surpass those of clinically used drugs. Aside from new natural products, application of these approaches to diverse bacteria has also unveiled small molecule elicitors and the underlying mechanisms through which they turn on microbial natural product biosynthesis.
Mohammad R. Seyedsayamdost is Professor of Chemistry and Molecular Biology at Princeton University. He obtained a combined B.S./M.S. degree in Biochemistry from Brandeis University, completing his thesis research with Prof. Liz Hedstrom. He then conducted graduate research under the guidance of Prof. JoAnne Stubbe and received a Ph.D. in chemistry from MIT. After postdoctoral training with Prof. Jon Clardy and Prof. Roberto Kolter at Harvard Medical School, he started his independent career at Princeton. Prof. Seyedsayamdost's research has been recognized by a number of awards, most recently with the prestigious MacArthur Fellowship.