Ansamycins, such as rifamycin and ansamitocin, usually consist of a group of structural similar components. Geldanamycin, a benzenic ansamycin, has been found to consist of four structural similar components. We analyzed the geldanamycin (GDM) preparation from Streptomyces hygroscopicus 17997 by LC-ESI(+)-MS/MS, and discovered five novel and one known GDM analogues in trace amounts. Based on the ESI(+)-MS/MS spectra of these GDM analogues, and the present understanding of GDM biosynthesis, we proposed the possible chemical structures of these GDM analogues. Three novel GDM analogues, all having the same molecular formula of C29H42N2O10, were GDM biosynthetic derivatives with one of the three C-C double bonds between C2-C3, C4-C5 and C8-C9 in GDM changed to mono-hydroxylated C-C single bond. The other two novel GDM analogues, having the same molecular formula of C28H38N2O8, were 17(or 12, or 4)-desmethoxylgeldanamycin and 4,5-dihydro-10,11-dehydrate-17-desmethyl-17-hydroxylgeldanamycin, respectively. The known GDM analogue, having the molecular formula of C29H42N2O9, was 4, 5-dihydrogeldanamycin, an intermediate in GDM biosynthesis. The discovery of novel GDM analogues provided us new insights in understanding the biosynthetic details of GDM, and clues of obtaining GDM derivatives by gene-disruption and combinatorial biosynthesis.
Anti-Bacterial Agents ; chemistry ; Benzoquinones ; analysis ; chemistry ; Chromatography, Liquid ; methods ; Lactams, Macrocyclic ; analysis ; chemistry ; Tandem Mass Spectrometry ; methods