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

J Antibiot (Tokyo). 2015 Feb;68(2):126-32. doi: 10.1038/ja.2014.100. Epub 2014 Aug 6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cholesterol / metabolism
  • Cholesterol Esters / antagonists & inhibitors*
  • Cholesterol Esters / biosynthesis
  • Chromatography, High Pressure Liquid
  • Cricetinae
  • Cricetulus
  • HeLa Cells
  • Humans
  • Inhibitory Concentration 50
  • Lysosomes / drug effects
  • Lysosomes / metabolism
  • Macrolides / administration & dosage
  • Macrolides / isolation & purification
  • Macrolides / pharmacology*
  • Macrophages, Peritoneal / drug effects*
  • Macrophages, Peritoneal / metabolism
  • Mice
  • Streptomyces / metabolism*
  • Vacuolar Proton-Translocating ATPases / drug effects*
  • Vacuolar Proton-Translocating ATPases / metabolism


  • Cholesterol Esters
  • Macrolides
  • bafilomycin L
  • bafilomycin C1
  • Cholesterol
  • Vacuolar Proton-Translocating ATPases