Genome mining based on transcriptional regulatory networks uncovers a novel locus involved in desferrioxamine biosynthesis
Fig 3
New model for biosynthesis of desferrioxamines B and E.
a, Extracted ion chromatograms for m/z values corresponding to DFO-related metabolites in culture extracts of the knock-out mutants of SCO4048 (desJ), SCO4049 (desG), and SCO40450 (desH) compared to the parent Streptomyces coelicolor M145 strain. The desG mutant fails to produce DFOB, while a 16-fold decrease in DFOB biosynthesis was seen in desH mutants (cf. S3 Fig). Details on the mass spectrometry data can be found at https://zenodo.org/records/15106944. b, Proposed biosynthetic pathway for assembly of desferrioxamines E and B. Main biosynthetic enzymes presented in bold face. DesG and DesH balance intracellular N-hydroxy-N-succinylcadaverine (HSC) and N-hydroxy-N-acetylcadaverine (HAC) concentrations by converting HSC to HAC. In the absence of DesG and/or DesH, the cells likely fail to produce sufficient levels of HAC, thereby strongly attenuating the production of DFOB. Although DesC has been shown to be able to catalyze the acetylation of N-hydroxycadaverine in vitro, the enzyme can only modestly compensate for the loss of DesH in vivo, underlining the important role played by DesG and DesH in DFOB production (S4 Fig).