A new 16-membered tetraene macrolide JBIR-100 from a newly identified Streptomyces species

Ueda, Junichi; Hashimoto, Junko; Yamamura, Hideki; Hayakawa, Masayuki; Takagi, Motoki; Shin‐ya, Kazuo

doi:10.1038/ja.2011.20

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“…The bafilomycin family has a common 16-membered lactone ring with two conjugated diene moieties at the same positions and the same side chains at C-6, C-7, C-8 and C-14 ( Figure 1). This family includes 14 bafilomycins, 11,[20][21][22] hygrolidin, 23 setamycin, 24,25 hygrobafilomycin, 12 JBIR-100 26 and makinolides, 27,28 all of which are produced by Streptomyces strains. As elucidated in this study, BFL has two structural characteristics: (1) a methyl residue at C-2 like makinolides, JBIR-100, bafilomycin K and J, but on an O-methyl residue at C-2 in other members, and (2) a 2H-pyran at C-18, but a tetrahydropyran or a dihydropyran at C-18 in other members.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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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.

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