Inhibition of acyl-CoA: cholesterol acyltransferase by isohalobacillin, a complex of novel cyclic acylpeptides produced by Bacillus sp. A1238.
A complex of metabolites consisting of two isomeric cyclic acylpeptides was isolated from a culture of Bacillus sp. A1238 by successive chromatographies on Amberlite XAD-7, silica gel and silica ODS columns. By a combination of spectroscopic and chemical analyses, the two subcomponents were identified as isomers of halobacillin, and the complex was designated isohalobacillin. Each molecule of isohalobacillin subcomponents contains either a 3-hydroxy-1-oxo-13-methyltetradecyl or a 3-hydroxy-1-oxo-12 methyltetradecyl moiety in place of a 3-hydroxy-1-oxopentadecyl moiety that is found in the halobacillin molecule. In a cell-free assay, isohalobacillin inhibited acyl-CoA: cholesterol acyltransferase by 50% at a concentration of 50 microM. When added to a culture of macrophage J774, the agent inhibited oxidized low density lipoprotein-induced synthesis of cholesteryl ester from [14C]oleate without affecting surface binding, internalization and degradation of the lipoprotein in the cells.
Hasumi
K
K
Department of Applied Biological Science, Tokyo Noko University, Japan.
Takizawa
K
K
Takahashi
F
F
Park
J K
JK
Endo
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001407:Bacillus / Q000378:metabolism*; D002474:Cell-Free System; D002788:Cholesterol Esters / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008074:Lipoproteins / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013057:Spectrum Analysis; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*
D002788:Cholesterol Esters; D004791:Enzyme Inhibitors; D008074:Lipoproteins; D010456:Peptides, Cyclic; C097795:isohalobacillin; D002785:Sterol O-Acyltransferase