DETERMINATION OF THE STRUCTURE OF EXOCHELIN MN, THE EXTRACELLULAR SIDEROPHORE FROM MYCOBACTERIUM-NEOAURUM

Background: Siderophores are compounds produced by bacteria to acquire iron. Exochchelin MN, the extracellular siderophore from Mycobacteriu m neoaurum, is of particular interest because it has been shown to tra nsport iron into M. leprae, which is responsible for the disease lepro sy. Exochelins from other species cannot mediate iron transport in M. leprae, suggesting a specific uptake mechanism involving exochelin MN. We set out to determine the structure of exochelin MN and identify th e features of the molecule that may account for this specificity. Resu lts: The structure of exochelin MN was elucidated by a combination of techniques including nuclear magnetic resonance, mass spectrometry, de rivatization and gas chromatography. Exochelin MN is a peptide, contai ning the unusual amino acid beta-hydroxyhistidine and an unusual N-met hyl group. The peptide coordinates iron(III) octahedrally using its tw o cis-hydroxamate groups plus the hydroxyl and imidazole nitrogen of t he beta-hydroxyhistidine. The three-dimensional structure of the hexad entate exochelin/gallium complex was deduced from NMR data. Conclusion s: Exochelin MN has some structural features in common with other side rophores, but has a unique three-dimensional structure, which is presu mably important for its specific activity in M. leprae. Exochelin MN m ay be a target for drug design in the fight against infection with thi s pathogen.