Princeton Chemists Solve Structure of Macrocyclic Peptide Involved in Quorum-Sensing Communication in Streptococci; Peptide Contains Unprecedented Carbon-Carbon Cross-Link Between Lysine and Tryptophan

Bacteria speak to one another using peptide signals in a soundless language known as quorum sensing. In a step towards translating bacterial communications, researchers at Princeton University have revealed the structure and biosynthesis of streptide, a peptide involved in the quorum sensing system common to many Streptococci. "It's extremely rare for one research group to do both natural products discovery and mechanistic enzymology," said Leah Bushin (photo), a member of the laboratory of Mohammad Seyedsayamdost, Ph.D., and co-first author on the article published in the May 2015 issue of Nature Chemistry. The article is titled “"Structure and Biosynthesis of a Macrocyclic Peptide Containing an Unprecedented Lysine-to-Tryptophan Crosslink." Ms. Bushin worked on elucidating the structure of streptide as part of her undergraduate senior thesis project and will enter Princeton Chemistry's graduate program in the fall. To explore how bacteria communicate, Ms. Bushin first had to grow them, a challenging process in which oxygen had to be rigorously excluded. Next, she isolated the streptide and analyzed it using two-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopy, a technique that allows scientists to deduce the connections between atoms in a molecule by pulsing their nuclei with powerful magnets to pulse atomic nuclei. The experiments revealed that streptide contained an unprecedented crosslink between two unactivated carbons on lysine and tryptophan, constituting a new class of macrocyclic peptides. "We didn't think it would be as cool as a carbon-carbon bond between two amino acid side chains, so it was definitely a surprise," said Ms. Bushin. To figure out how this novel bond was being formed, the researchers took a closer look at the gene cluster that produces streptide.
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