An elastic siderophore synthetase and rubbery substrates assemble multimeric linear and macrocyclic hydroxamic acid metal chelators.

The trihydroxamic acid bacterial siderophore desferrioxamine B (DFOB, 1) produced by the DesABCD biosynthetic cluster coordinates metals beyond Fe(iii), which identifies potential to modify this chelator type to broaden metal sequestration and/or delivery applications. Rather than producing discrete chelators by total chemical synthesis from native monomers including -hydroxy--succinyl-cadaverine (HSC, 2), the recombinant siderophore synthetase from CNB-440 (DesD) was used with different substrate combinations to produce biocombinatorial mixtures of hydroxamic acid chelators. The mixtures were screened with Ga(iii) or Zr(iv) as surrogates of immunological positron emission tomography (PET) imaging radiometals Ga(iii) or Zr(iv) to inform known or new coordination chemistry.

Acetyl-CoA-Mediated Post-Biosynthetic Modification of Desferrioxamine B Generates - and N--Acetylated Isomers Controlled by a pH Switch.

Biosynthesis of the hydroxamic acid siderophore desferrioxamine D (DFOD, ), which is the -acetylated analogue of desferrioxamine B (DFOB, ), has been delineated. Enzyme-independent Ac-CoA-mediated -acetylation of produced , in addition to three constitutional isomers containing an N--acetyl group installed at either one of the three hydroxamic acid groups of . The formation of -Ac-DFOB (DFOD, ) and the composite of N--acetylated isomers N--Ac-DFOB[001] (), N--Ac-DFOB[010] (), and N--Ac-DFOB[100] () (defined as the N--Ac motif positioned within the terminal amine, internal, or -acetylated region of , respectively), was pH-dependent, with - dominant at pH < 8.

The chemical biology and coordination chemistry of putrebactin, avaroferrin, bisucaberin, and alcaligin.

Dihydroxamic acid macrocyclic siderophores comprise four members: putrebactin (putH), avaroferrin (avaH), bisucaberin (bisH), and alcaligin (alcH). This mini-review collates studies of the chemical biology and coordination chemistry of these macrocycles, with an emphasis on putH. These Fe(III)-binding macrocycles are produced by selected bacteria to acquire insoluble Fe(III) from the local environment.

Dimeric and trimeric homo- and heteroleptic hydroxamic acid macrocycles formed using mixed-ligand Fe(III)-based metal-templated synthesis.

Macrocyclic hydroxamic acids coordinate Fe(III) with high affinity as part of siderophore-mediated bacterial iron acquisition. Trimeric hydroxamic acid macrocycles, such as desferrioxamine E (DFOE), are prevalent in nature, with fewer dimeric macrocycles identified, including putrebactin (pbH), avaroferrin (avH), bisucaberin (bsH) and alcaligin (alH). This work used metal-templated synthesis (MTS) to pre-assemble complexes between one equivalent of Fe(III) and two equivalents of 4-((4-aminobutyl)(hydroxy)amino)-4-oxobutanoic acid (BBH) or 4-((5-aminopentyl)(hydroxy)amino)-4-oxobutanoic acid (PBH).