Conglobatin

Fermentation of deposited cultures of Streptomyces conglobatus, known to produce the polyether antibiotic, ionomycin has resulted in the isolation and characterization of a second metabolite, conglobatin (C28H38N2O6). X-Ray analysis revealed a dimeric macrolide dilactone structure for conglobatin, similar to the structures of the mold metabolites vermiculin and pyrenophorin, from which the absolute configuration of conglobatin has been inferred. The dimer consists of two molecules of 7-hydroxy-8-oxazoyl-2,4,6-trimethyl-2-octenoic acid joined by two ester linkages.

Chemical investigation of a previously unreported indigenous Australian Streptomyces strain MST-91080 has identified six novel analogues related to the oxazole-pendanted macrodiolide, conglobatin. Phylogenetic analysis of the 16S rRNA gene sequence identified MST-91080 as a species of Streptomyces, distinct from reported conglobatin producer, Streptomyces conglobatus ATCC 31005. Conglobatins B-E diverge from conglobatin through differing patterns of methylation on the macrodiolide skeleton. The altered methyl positions suggest a deviation from the published biosynthetic pathway, which proposed three successive methylmalonyl-CoA extender unit additions to the conglobatin monomer. Conglobatins B1, C1 and C2 exhibited more potent cytotoxic activity selectively against the NS-1 myeloma cell line (IC500.084, 1.05 and 0.45 µg ml-1, respectively) compared with conglobatin (IC501.39 µg ml-1).

Two new isochromans, panowamycins A and B, were purified by solvent extraction, silica gel and octadecylsilyl silica gel (ODS) column chromatography followed by preparative HPLC, from a culture broth of Streptomyces sp. K07-0010, together with the known compounds NFAT-133, conglobatin, piericidin C series and dinactin. Structures of panowamycins were elucidated as new analogs of NFAT-133 by spectroscopic studies including various NMR experiments. Panowamycins A and B showed moderate antitrypanosomal activity, with IC(50) values of 0.40 and 3.30 μg ml(-1), respectively.