Cerulenin

Cerulenin is an antifungal antibiotic that inhibits sterol and fatty acid biosynthesis. In fatty acid synthesis, it has been reported to bind in equimolar ratio to b-keto-acyl-ACP synthase, one of the seven moieties of fatty acid synthase, blocking the interaction of malonyl-CoA. It also has the related activity of stimulating fatty acid oxidation through the activation of CPT1, another enzyme normally inhibited by malonyl-CoA. Inhibition involves covalent thioacylation that permanently inactivates the enzymes.^[1] These two behaviors may increase the availability of energy in the form of ATP, perhaps sensed by AMPK, in the hypothalamus.^[2] In sterol synthesis, cerulenin inhibits HMG-CoA synthetase activity.^[3] Cerulenin causes a dose-dependent decrease in HER2/neu protein levels in breast cancer cells, from 14% at 1.25 to 78% at 10 milligrams per liter, and targeting of fatty acid synthase by related drugs has been suggested as a possible treatment. ^[4] Antiproliferative and pro-apoptotic effects have been shown in colon cells as well.^[5] At an intraperitoneal dose of 30 milligrams per kilogram, it has been shown to inhibit feeding and induce dramatic weight loss in mice by a mechanism similar to, but independent or downstream of, leptin signaling.^[6] It is found naturally in the industrial strain 'Cephalosporium caerulens' (Sarocladium oryzae, the sheath rot pathogen of rice).

References

1. ^ Straub SG, Yajima H, Komatsu M, Aizawa T, Sharp GW. The effects of cerulenin, an inhibitor of protein acylation, on the two phases of glucose-stimulated insulin secretion. Diabetes. 2002 Feb;51 Suppl 1:S91-5.
2. ^ reviewed in PMID 17021367
3. ^ PMID 4157441
4. ^ PMID 15235125
5. ^ Huang P, Zhu S, Lu S, Dai Z, Jin Y.] An experimental study on cerulenin induced apoptosis of human colonic cancer cells. PMID 11866903 Zhonghua Bing Li Xue Za Zhi. 2000 Apr;29(2):115-8.
6. ^ PMID 12028418