Cerulenin inhibition of lipid synthesis and its reversal by exogenous fatty acids in Mycobacterium smegmatis ATCC 607.
Cerulenin inhibited the lipid synthesis of Mycobacterium smegmatis ATCC 607 over the range of 0.5-1.8 microgram/mL with complete inhibition at 1.8 microgram/mL, as monitored by [14C]glycerol incorporation into lipids. Exogenous fatty acids failed to restore the lipid synthesis at 1.8 microgram/mL; however, the addition of palmitic acid to the growth medium partially restored the lipid synthesis when cerulenin concentration was decreased to 1.6 microgram/mL. Fatty acid analysis of cerulenin plus palmitic acid supplemented cultures revealed that exogenously supplied fatty acid was incorporated into cellular phospholipids. Further investigations with 1.6 microgram/mL of cerulenin and [14C]acetate and [32P]orthophosphoric acid showed that cerulenin inhibited the synthesis of saturated plus unsaturated fatty acids and phospholipids. Pulse-chase studies with [14C]acetate revealed decreased synthesis and degradation of each of the phospholipid components.
D000935:Antifungal Agents / Q000494:pharmacology*; D002569:Cerulenin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology*; D008563:Membrane Lipids / Q000378:metabolism; D009161:Mycobacterium / Q000187:drug effects* / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism
D000935:Antifungal Agents; D005227:Fatty Acids; D008563:Membrane Lipids; D010743:Phospholipids; D002569:Cerulenin