Engineering a cleavable disulfide bond into a natural product siderophore using precursor-directed biosynthesis
Tomas Richardson-Sanchez1, Rachel Codd
1The University of Sydney, School of Medical Sciences (Pharmacology) and Bosch Institute, Camperdown, New South Wales 2006, Australia. rachel.codd@sydney.edu.au.
Chemical Communications (Cambridge, England)
|August 15, 2018
Summary
Researchers created a modified bacterial siderophore, desferrioxamine B (DFOB), with a disulfide bond. This new compound and its breakdown products show potential for novel antibiotic and nanotechnology applications.
Area of Science:
- Microbiology
- Biochemistry
- Materials Science
Background:
- Bacterial siderophores like desferrioxamine B (DFOB) are crucial for iron uptake.
- Modifying siderophore structures can lead to novel applications.
Purpose of the Study:
- To synthesize a disulfide-containing analogue of DFOB.
- To investigate its properties and potential applications in medicine and nanotechnology.
Main Methods:
- Production of the DFOB analogue (DFOB-(SS)1[001]) using Streptomyces pilosus cultures supplemented with cystamine.
- Demonstration of cystamine's competitive inhibition against native 1,5-diaminopentane during biosynthesis.
- Cleavage studies of DFOB-(SS)1[001] and its metal complexes (Fe(iii), Ga(iii)) using dithiothreitol.
Main Results:
- Successful synthesis of DFOB-(SS)1[001] via microbial fermentation.
- Confirmation of cystamine's role in altering the siderophore assembly pathway.
- Demonstration of the disulfide bond's susceptibility to reductive cleavage by dithiothreitol.
Conclusions:
- The novel disulfide-containing DFOB analogue, DFOB-(SS)1[001], can be produced through microbial fermentation.
- This analogue and its thiol-containing cleavage products hold promise for developing new antibiotic strategies.
- Potential applications exist in gold-sulfur (Au-S) based nanotechnologies.
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