报告人：Dr. Mohammad R. Seyedsayamdost Associate Professor Department of Chemistry, Princeton University, Princeton, NJ
邀请人：林双君教授 （ email@example.com
Dr. Mohammad R. Seyedsayamdost got his Ph.D at MIT under the guidance of Prof. JoAnne Stubbe. His PhD thesis combined methods for site-specific incorporation of unnatural amino acids with rapid kinetic and spectroscopic techniques in order to examine the mechanism of ribonucleotide reductase, an essential metalloenzyme in all living cells. He then joined the labs of Prof. Jon Clardy and Prof. Roberto Kolter at Harvard Medical School, where he examined the roles of small molecules in mediating microbial interspecies interactions. He started as an assistant professor in the Department of Chemistry at Princeton University in 2013. His lab is interested in the discovery, structure, function, and biosynthesis of new small molecules with bioactive or therapeutic properties. These studies blend approaches from microbiology, bacterial genetics, small molecule chemistry, biochemistry, and mechanistic enzymology.
Microbial natural products serve as a dominant source of pharmaceutical compounds and comprise some of our most celebrated cures. Recent studies, however, have been plagued by the frequent rediscovery of old molecules. The underlying reason is that the vast majority of natural product biosynthetic genes in a given bacterium are not significantly expressed, when cultured under standard laboratory conditions. These so-called ‘silent’ or ‘cryptic’ gene clusters represent a large reservoir of bioactive molecules and methods that access them would have a profound impact on natural products 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. Application of these approaches to diverse bacteria has unveiled not only the products of silent gene clusters, but also small molecule elicitors, which in most cases are growth-inhibitory or antibiotic in nature. These insights have led to the idea that old antibiotics may be used to find new ones. In addition, my group has been engaged in elucidating new transformations carried out by metalloenzymes during natural product biosynthesis. Recent reactions that we have discovered, along with proposed mechanisms, will be presented as well.