Abstract

Analogues of the trimeric hydroxamic acid siderophore desferrioxamine B (DFOB) were characterized from cultures of Streptomyces pilosus cosupplemented with 10:10 mM oxobis(ethanamine) (OBEA)/thiobis(ethanamine) (TBEA). The exogenous diamines OBEA and TBEA competed against native 1,5-diaminopentane during assembly to produce DFOB and 26 analogues of DFOB that contained all possible combinations of oxo-, thio-, and methylene groups threaded along the DFOB backbone. The total number of observed compounds (27) matched the theoretical maximum (xy) that could be assembled from three substrates (x = 3) to form a trimeric siderophore (y = 3). The LC capacity factors of 1−27 correlated well with c log P or c log D7.4 values. Mixed-substrate precursor-directed biosynthesis has the potential to significantly expand the structural diversity of siderophores to yield molecules with new properties.