93898-36-3Relevant academic research and scientific papers
Erythrochelin-a hydroxamate-type siderophore predicted from the genome of Saccharopolyspora erythraea
Robbel, Lars,Knappe, Thomas A.,Linne, Uwe,Xie, Xiulan,Marahiel, Mohamed A.
, p. 663 - 676 (2010)
The class of nonribosomally assembled siderophores encompasses a multitude of structurally diverse natural products. The genome of the erythromycin- producing strain Saccharopolyspora erythraea contains 25 secondary metabolite gene clusters that are mostly considered to be orphan, including two that are responsible for siderophore assembly. In the present study, we report the isolation and structural elucidation of the hydroxamate-type tetrapeptide siderophore erythrochelin, the first nonribosomal peptide synthetase-derived natural product of S. erythraea. In an attempt to substitute the traditional activity assay-guided isolation of novel secondary metabolites, we have employed a dedicated radio-LC-MS methodology to identify nonribosomal peptides of cryptic gene clusters in the industrially relevant strain. This methodology was based on transcriptome data and adenylation domain specificity prediction and resulted in the detection of a radiolabeled ornithine-inheriting hydroxamate-type siderophore. The improvement of siderophore production enabled the elucidation of the overall structure via NMR and MSn analysis and hydrolysate-derivatization for the determination of the amino acid configuration. The sequence of the tetrapeptide siderophore erythrochelin was determined to be d-α-N-acetyl-δ-N-acetyl-δ-N-hydroxyornithine- d-serine-cyclo(l-δ-N-hydroxyornithine-l-δ-N-acetyl-δ-N- hydroxyornithine). The results derived from the structural and functional characterization of erythrochelin enabled the proposal of a biosynthetic pathway. In this model, the tetrapeptide is assembled by the nonribosomal peptide synthetase EtcD, involving unusual initiation-and cyclorelease- mechanisms.
