PI: Collin Stultz, Department of Electrical Engineering & Computer Science, MIT
Microcin-C (McC), a potent antimicrobial compound produce by some strains of Escherichia coli, consists of a heptapeptide that is covalently linked through a C-terminal Aspartate residue to a modified AMP moiety. After being transported to the bacterial cytoplasm, McC is cleaved via intracellular aminopeptidases yielding a modified aspartyl-adenylate compound that inhibits bacterial aspartyl-tRNA synthetase. While the peptide portion of McC facilitates active transport across the inner membrane of E. coli through binding the YejABEF transporter, it does not have antimicrobial properties in and of itself. In this work we exploit the results of recent computational studies to develop and test a strategy for designing variants of the N-terminal peptide portion of McC, yielding mutants that have new antimicrobial properties. The goal is to produce novel McC-like compounds that both inhibit aspartyl-tRNA synthetase and that compromise the integrity of the bacterial plasma membrane.