Bafilomycin L, a new inhibitor of cholesteryl ester synthesis in mammalian cells, produced by marine-derived Streptomyces sp. OPMA00072

Abstract

Marine-derived Streptomyces sp. OPMA00072 was found to produce inhibitors of the synthesis of neutral lipids in a cell-based assay using Chinese hamster ovary (CHO) cells. A new 16-membered macrolide named bafilomycin L (BFL) (1) was isolated along with the known structurally related bafilomycin C1 (BFC1) (3) from the culture broth of the actinomycete by solvent extraction, octadecylsilyl column chromatography and HPLC. BFL inhibited cholesteryl ester (CE) synthesis in CHO cells with an IC50 value of 0.83 nM and also in mouse peritoneal macrophages with an IC50 of 6.1 nM. In addition, BFL blocked cellular acidification in HeLa cells by interfering with vacuolar H(+)-ATPase (V-ATPase) as well as other bafilomycins. These data strongly suggest that BFL disturbed the lysosome function to block cholesterol metabolism, leading to the inhibition of CE accumulation in mammalian cells.

Graphiumins, new thiodiketopiperazines from the marine-derived fungus Graphium sp. OPMF00224

“…DNA extraction, PCR, sequencing and Basic Local Alignment Search Tool searching followed. 16,17 The primer set ITS-5 (5′-GGAAGTAAAAGTCGTAACAAGG-3′) and NL-4 (5′-GGTCCGTGTTTCAAGACGG-3′) was used to amplify the region under the conditions of 30 cycles at 94°C for 30 s, 60°C for 30 s and 72°C for 90 s. The sequence is available at the DNA Data Bank of Japan/European Molecular Biology Laboratory/GenBank databases under the accession number AB934385. On the basis of the Basic Local Alignment Search Tool search and its microscopic features, the strain was identified as a Graphium sp.…”

Marine natural products

“…isolated from litter at a river mouth. 60 Following genetic manipulation of a marine Streptomyces olivaceus by disruption of orf-1741, a putative transcriptional gene, three halogenated dibenzoxazapinone derivatives, the mycemycins C-E 62-64, were isolated from the mutant strain and are the rst dibenzoxazapinones produced from a microbial source. 61 Marine Actinobacteria continue to surprise with the versatility of their biosynthetic machinery.…”

Biological characterization of the hygrobafilomycin antibiotic JBIR-100 and bioinformatic insights into the hygrolide family of natural products

“…However, while bafilomycin B 1 and bafilomycin C 1 have antibacterial activity, bafilomycin A 1 displays no detectable antibacterial activity [2]. Similarly, a recent report found that bafilomycin L, which does not contain a fumarate moiety, has no antibiotic activity [6]. These observations lead us to speculate that the fumarate might contribute to antibacterial activity and we thus determined the minimum inhibitory concentration (MIC) of JBIR-100 against a number of bacteria.…”