BACTERIA SPEAK TO ONE ANOTHER using a soundless language known as quorum sensing. In a step toward translating bacterial communications, researchers have revealed the structure and biosynthesis of streptide, a signaling molecule involved in the quorum sensing system common to many diseasecausing streptococci bacteria.
The research team included undergraduate Leah Bushin, who was the co-first author on an article published on April 20, 2015, in Nature Chemistry. Bushin helped determine the structure of streptide as part of her undergraduate senior thesis project.
To explore how bacteria communicate, first she 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 nuclear magnetic resonance (NMR) spectroscopy, a technique that allows scientists to deduce the connections between atoms.
The experiments revealed that streptide contains an unprecedented crosslink between two unactivated carbons on the amino acids lysine and tryptophan. To figure out how this novel bond was being formed, the researchers took a closer look at the gene cluster that produces streptide. Within the gene cluster, they suspected that a radical S-adenosyl methionine (SAM) enzyme, which they dubbed StrB, could be responsible for this unusual modification.
“Radical SAM enzymes catalyze absolutely amazing chemistries,” said Kelsey Schramma, a graduate student and the other co-first author on the article. The team showed that one of the iron-sulfur clusters reductively activated one molecule of SAM, kicking off a chain of one-electron (radical) reactions that gave rise to the novel carbon-carbon bond.
“The synergy between Leah and Kelsey was great,” said Mohammad Seyedsayamdost, an assistant professor of chemistry who led the research, which was supported by the National Institutes of Health. “They expressed interest in complementary aspects of the project, and the whole ended up being greater than the sum of its parts,” he said.
Future work will target streptide’s biological function — its meaning in the bacterial language — as well as confirming its production by other streptococcal bacteria strains.
–By Tien Nguyen