George and Pauline Watt Centennial Lectureship - Alison Butler

Many microorganisms acquire iron using siderophore ligands with catecholate, hydroxamate, α-hydroxycarboxylate, and diazeniumdiolate coordinating groups. Through mining microbial genomes, specific classes of siderophores can be identified based on the Fe(III)-binding groups.  In the large class of peptidic siderophores, b-hydroxyaspartate is often present as an Fe(III)-binding ligand. Biosynthesis of b-hydroxyaspartate is intriguing in regards to the stereoselective control of hydroxylation catalyzed by non heme Fe enzymes. The origin of the b-hydroxyaspartate diastereomers in these siderophores is revealed in the microbial genomes.  A new class of tris catechol siderophores in marine and pathogenic microbes is based on a variation of enterobactin, adding a combinatoric suite of D- and L- cationic amino acids.  Variation in amino acid chirality directs stereochemistry at the Fe(III) site, which in turn profoundly affects microbial growth.  Most recently a new class of siderophores containing a Fe(III)-binding diazeniumdiolate ligand has been discovered. The biosynthesis of the amino acid graminine, which harbors the diazeniumdiolate, is catalyzed by other iron enzymes. While microbial genome mining encompasses microbes from all environments, marine microbes are found to be prominent in our investigations into the discovery, biosynthesis and reactivity of new b-hydroxyaspartate, triscatecholate, and diazeniumdiolate siderophores. These and further developments on the bioinorganic chemistry of these siderophores will be presented.