Title | Structure and biosynthesis of amychelin, an unusual mixed-ligand siderophore from Amycolatopsis sp. AA4. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Seyedsayamdost, MR, Traxler, MF, Zheng, S-L, Kolter, R, Clardy, J |
Journal | J Am Chem Soc |
Volume | 133 |
Issue | 30 |
Pagination | 11434-7 |
Date Published | 2011 Aug 03 |
ISSN | 1520-5126 |
Keywords | Actinomycetales, Crystallography, X-Ray, Iron, Ligands, Models, Molecular, Molecular Structure, Phenotype, Siderophores |
Abstract | <p>Actinobacteria generate a large number of structurally diverse small molecules with potential therapeutic value. Genomic analyses of this productive group of bacteria show that their genetic potential to manufacture small molecules exceeds their observed ability by roughly an order of magnitude, and this revelation has prompted a number of studies to identify members of the unknown majority. As a potential window into this cryptic secondary metabolome, pairwise assays for developmental interactions within a set of 20 sequenced actinomycetes were carried out. These assays revealed that Amycolatopsis sp. AA4, a so-called "rare" actinomycete, produces a novel siderophore, amychelin, which alters the developmental processes of several neighboring streptomycetes. Using this phenotype as an assay, we isolated amychelin and solved its structure by NMR and MS methods coupled with an X-ray crystallographic analysis of its Fe-complex. The iron binding affinity of amychelin was determined using EDTA competition assays, and a biosynthetic cluster was identified and annotated to provide a tentative biosynthetic scheme for amychelin.</p> |
DOI | 10.1021/ja203577e |
Alternate Journal | J Am Chem Soc |
PubMed ID | 21699219 |
PubMed Central ID | PMC3144690 |
Grant List | R01 GM082137 / GM / NIGMS NIH HHS / United States K99 GM098299 / GM / NIGMS NIH HHS / United States R01 GM086258 / GM / NIGMS NIH HHS / United States U54 AI057159 / AI / NIAID NIH HHS / United States GM82137 / GM / NIGMS NIH HHS / United States 5F32GM089044-02 / GM / NIGMS NIH HHS / United States F32 GM089044 / GM / NIGMS NIH HHS / United States GM086258 / GM / NIGMS NIH HHS / United States AI057159 / AI / NIAID NIH HHS / United States |