Almost all bacteria require iron for growth, but iron is insoluble in aerobic environments. Bacteria often produce siderophores — small-molecule chelators — to obtain iron. Siderophore discovery is aided by scanning genomes for biosynthetic pathways, though current techniques leave ambiguities in the predicted structures which must be rectified experimentally. Some peptidic siderophores contain the chelating amino acid β-hydroxyaspartate (β-OHAsp). A family of Fe(II)/α-ketoglutarate-dependent dioxygenases is responsible for the hydroxylation of Asp while the amino acid is attached to the nonribosomal peptide synthetase (NRPS), but predicting the regio- and stereoselectivity of hydroxylation has not been possible. To develop refined genomic tools for predicting siderophore structures, we analyzed gene clusters responsible for the biosynthesis of known siderophores. Clear functional subtypes of β-hydroxylases emerged with divergent reactivity, which we corroborate with phylogenetic analysis. Mapping characterized β-OHAsp diastereomers in siderophores to the phylogenetic tree of β-hydroxylases yields the first methods to predict β-OHAsp stereochemistry <i>in silico</i>.

Genomic analysis of siderophore Fe(II)/α-ketoglutarate-dependent Aminoacyl β-Hydroxylases reveals functional subtypes

2019 Fall National Meeting

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