Friday, April 25, 2008
Synthesis of Asymmetric Derivatives of Enterobactin
Nohemy Sorto, MARC U*STAR Scholar
Bacteria and other living organisms need iron to survive; therefore, when exposed to an iron deficient environment, bacteria synthesize and secrete siderophores (iron chelators). Enterobactin is a siderophore produced by E.Coli to deliver ferric iron into the bacterial cell. Ferric iron is transported into the cell through the outer membrane protein, FepA, and the inner membrane protein, the FepB. Ultimately, the iron is released into the periplasm via the FepC receptor.
Our group is interested in the iron release mechanisms utilized by E.Coli. There are two proposed mechanisms for ferric iron release. According to the first mechanism, iron is released due to the hydrolysis of the trilactone backbone by a specific esterase. However, it has been shown that analogs of enterobactin, which do not contain hydrolysable backbones, still promote bacterial growth. Therefore, the second mechanism that has been proposed is based on the sequential protonation of the complex at a low periplasmic pH. We have synthesized derivatives of enterobactin to study the hypothesis of sequential protonation of the m-phenolic oxygens involved in the iron release mechanism. The target molecules will mimic the intermediates in