Triacsin C is a fungal metabolite from Streptomyces aureofaciens which almost completely inhibits de novo synthesis of triacylglycerol and phospholipid. This compound specifically inhibits the activity of long chain acyl-CoA synthetase 1 and 4 (IC50~8µM) but has no effect on the activity of acyl-CoA synthetase 5, in intact cells and in cell lysates. Inhibition of these enzymes causes a decrease in the cellular levels of acyl-CoA precursors for lipid synthesis activity, cell proliferation and lipid transformation. Kinetic analysis indicates that inhibition of acyl-CoA synthetase by Triacsin C is not competitive with respect to the two substrates of acyl-CoA synthetase (ATP and coenzyme A), but is competitive with respect to long-chain fatty acids. The N-hydroxytriazene moiety of Triacsin C has been suggested to be essential for the inhibitory activity against acyl-CoA synthetase.
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