Structural characterization of daptomycin analogues A21978C1-3(d-Asn11) produced by a recombinant Streptomyces roseosporus strain.
Three daptomycin-related lipopeptides, A21978C1-3(d-Asn11) (2-4), were purified from the fermentation broth of a recombinant Streptomyces roseosporus strain. Their chemical structures were determined by analyses of the biosynthetic pathway, chemical transformations, d,l-amino acid quantitation by enantiomer labeling, tandem LC-MS/MS, and 2D-NMR techniques. Compounds 2-4 exhibited potent antibacterial activity against Staphylococcus aureus with MIC values of 0.6, 0.3, and 0.15 microM, respectively, well correlated to the acyl tail chain length.
Gu
Jian-Qiao
JQ
Cubist Pharmaceuticals, Inc., 65 Hayden Avenue, Lexington, Massachusetts 02421, USA. jian-qiao.gu@cubist.com
Nguyen
Kien T
KT
Gandhi
Chhayal
C
Rajgarhia
Vineet
V
Baltz
Richard H
RH
Brian
Paul
P
Chu
Min
M
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001216:Asparagine / Q000737:chemistry; D017576:Daptomycin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D030781:Organisms, Genetically Modified; D013211:Staphylococcus aureus / Q000187:drug effects; D013302:Streptomyces / Q000737:chemistry* / Q000235:genetics
D000900:Anti-Bacterial Agents; D001216:Asparagine; D017576:Daptomycin