Analogues of desferrioxamine B (DFOB) with new properties and new functions generated using precursor-directed biosynthesis

Thomas J. Telfer, Tomas Richardson-Sanchez, Michael P. Gotsbacher, Kate P. Nolan, William Tieu, Rachel Codd

Research output: Contribution to journalArticle

Abstract

Desferrioxamine B (DFOB) is a siderophore native to Streptomyces pilosus biosynthesised by the DesABCD enzyme cluster as a high affinity Fe(III) chelator. Although DFOB has a long clinical history for the treatment of chronic iron overload, limitations encourage the development of new analogues. This review describes a recent body of work that has used precursor-directed biosynthesis (PDB) to access new DFOB analogues. PDB exploits the native biosynthetic machinery of a producing organism in culture medium augmented with non-native substrates that compete against native substrates during metabolite assembly. The method allows access to analogues of natural products using benign methods, compared to multistep organic synthesis. The disadvantages of PDB are the production of metabolites in low yield and the need to purify complex mixtures. Streptomyces pilosus medium was supplemented with different types of non-native diamine substrates to compete against native 1,5-diaminopentane to generate DFOB analogues containing alkene bonds, fluorine atoms, ether or thioether functional groups, or a disulfide bond. All analogues retained function as Fe(III) chelators and have properties that could broaden the utility of DFOB. These PDB studies have also added knowledge to the understanding of DFOB biosynthesis.

LanguageEnglish
Pages395-408
Number of pages14
JournalBioMetals
Volume32
Issue number3
DOIs
Publication statusPublished - 1 Jun 2019

Keywords

  • Desferrioxamine B
  • Iron chelation
  • Natural product biosynthesis
  • Precursor-directed biosynthesis
  • Siderophore

ASJC Scopus subject areas

  • Biomaterials
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Metals and Alloys

Cite this

Telfer, Thomas J. ; Richardson-Sanchez, Tomas ; Gotsbacher, Michael P. ; Nolan, Kate P. ; Tieu, William ; Codd, Rachel. / Analogues of desferrioxamine B (DFOB) with new properties and new functions generated using precursor-directed biosynthesis. In: BioMetals. 2019 ; Vol. 32, No. 3. pp. 395-408.
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Analogues of desferrioxamine B (DFOB) with new properties and new functions generated using precursor-directed biosynthesis. / Telfer, Thomas J.; Richardson-Sanchez, Tomas; Gotsbacher, Michael P.; Nolan, Kate P.; Tieu, William; Codd, Rachel.

In: BioMetals, Vol. 32, No. 3, 01.06.2019, p. 395-408.

Research output: Contribution to journalArticle

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