University of California at Santa Barbara, USA
Discovering New Siderophores through Genome Mining
Through genomic screening we are identifying biosynthetic pathways for different classes of siderophores defined by variations in the chirality of amino acids, by the number and types of bidentate chelating groups, and by acylation with fatty acids [1,2]. Siderophores are ligands produced by bacteria to facilitate acquisition of iron, an element which is often required for growth, yet iron is not readily available in many environments in which microbes grow. One class of siderophores we are investigating consists of a tris-L-Ser or tetra-L-Ser scaffold with catechol groups for iron(III) coordination. Some have an intervening amino acid between the 2,3-dihydroxybenzoic acid catechol group and L-Ser consisting of a combinatoric suite of D- and L- amino acids (Figure 1). Variation in amino acid chirality affects the stereochemistry at the Fe(III) site. We are investigating the effect of chirality within the siderophore ligand and at the Fe(III) site on microbial growth and iron uptake. We are also investigating the effect of chirality in other types of siderophore ligands to discern where in the iron uptake process chiral discrimination is important.
 Reitz, Z.L., M. Sandy, M., and Butler, A., “Biosynthetic Considerations of Triscatechol Siderophores Framed on Serine and Threonine Macrolactone Scaffolds,” Metallomics, 2017, 9, 824-839.
 Kem, M.P., Zane, H.K., Springer, S.D. Gauglitz, J.M., and Butler, A., “Amphiphilic Siderophore Production by Oil-associating Microbes, Metallomics, 2014, 1150-1155.
 Hardy, C.D., and Butler, A., “β-hydroxyaspartic acid in siderophores: biosynthesis and reactivity,” J. Biol. Inorg. Chem. 2018, In Press. DOI: 10.1007/s00775-018-1584-2