Inhibition of unsaturated fatty acid synthesis in escherichia coli by the antibiotic cerulenin

Abstract

Low concentrations of cerulenin inhibit the growth of Escherichia coli by selectively blocking unsaturated fatty acid synthesis. This inhibition was relieved by unsaturated fatty acid supplements alone but not by saturated fatty acid supplements. The utilization of exogenous unsaturated fatty acids to sustain growth in the presence of cerulenin was confirmed by the analysis of bulk lipid composition. The effects of cerulenin on fatty acid synthesis were examined in vivo by pulse labeling with [14C]acetate and in vitro using [14C]malonyl-coenzyme A. In both cases, unsaturated fatty acid synthesis was inhibited by low concentrations of cerulenin with a stimulation of saturated fatty acid synthesis. Using mutant strains deficient in fatty acid synthesis, the effects of cerulenin on beta-ketoacyl-[acyl-carrier-protein] synthetases I and II were examined. Our results indicate that beta-ketoacyl-[acyl-carrier-protein] synthetase I is more sensitive to inhibition by cerulenin than beta-ketoacyl-[acyl-carrier-protein] synthetase II.