Structure and biosynthesis of amychelin, an unusual mixed-ligand siderophore from Amycolatopsis sp. AA4.

TitleStructure and biosynthesis of amychelin, an unusual mixed-ligand siderophore from Amycolatopsis sp. AA4.
Publication TypeJournal Article
Year of Publication2011
AuthorsSeyedsayamdost, MR, Traxler, MF, Zheng, S-L, Kolter, R, Clardy, J
JournalJ Am Chem Soc
Volume133
Issue30
Pagination11434-7
Date Published2011 Aug 03
ISSN1520-5126
KeywordsActinomycetales, 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>

DOI10.1021/ja203577e
Alternate JournalJ. Am. Chem. Soc.
PubMed ID21699219
PubMed Central IDPMC3144690
Grant ListR01 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