TY - JOUR
T1 - Structure and biosynthesis of amychelin, an unusual mixed-ligand siderophore from amycolatopsis sp. AA4
AU - Seyedsayamdost, Mohammad R.
AU - Traxler, Matthew F.
AU - Zheng, Shao Liang
AU - Kolter, Roberto
AU - Clardy, Jon
PY - 2011/8/3
Y1 - 2011/8/3
N2 - 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.
AB - 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.
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U2 - 10.1021/ja203577e
DO - 10.1021/ja203577e
M3 - Article
C2 - 21699219
AN - SCOPUS:79960880056
SN - 0002-7863
VL - 133
SP - 11434
EP - 11437
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 30
ER -