Cerulenin
Encyclopedia
Cerulenin is an antifungal
antibiotic
that inhibits fatty acid
and steroid 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. These two behaviors may increase the availability of energy in the form of ATP
, perhaps sensed by AMPK, in the hypothalamus
.
In sterol synthesis, cerulenin inhibits HMG-CoA synthetase activity. It was also reported that cerulenin specifically inhibited fatty acid biosynthesis in Saccharomyces cerevisiae
without having an effect on sterol formation.. But in general conclusion, cerulenin has inhibitory effects on sterol synthesis.
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. Antiproliferative and pro-apoptotic effects have been shown in colon cells as well. 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. It is found naturally in the industrial strain Cephalosporium caerulens (Sarocladium oryzae
, the sheath rot pathogen of rice).
Antifungal drug
An antifungal medication is a medication used to treat fungal infections such as athlete's foot, ringworm, candidiasis , serious systemic infections such as cryptococcal meningitis, and others...
antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
that inhibits fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
and steroid 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
Fatty acid synthase
Fatty acid synthase is an enzyme that in humans is encoded by the FASN gene.Fatty acid synthase is a multi-enzyme protein that catalyzes fatty acid synthesis...
, blocking the interaction of malonyl-CoA
Malonyl-CoA
Malonyl-CoA is a coenzyme A derivative.-Functions:It plays a key role in chain elongation in fatty acid biosynthesis and polyketide biosynthesis....
. 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. These two behaviors may increase the availability of energy in the form of ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
, perhaps sensed by AMPK, in the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
.
In sterol synthesis, cerulenin inhibits HMG-CoA synthetase activity. It was also reported that cerulenin specifically inhibited fatty acid biosynthesis in Saccharomyces cerevisiae
Saccharomyces cerevisiae
Saccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes...
without having an effect on sterol formation.. But in general conclusion, cerulenin has inhibitory effects on sterol synthesis.
Cerulenin causes a dose-dependent decrease in HER2/neu
HER2/neu
HER-2 also known as proto-oncogene Neu, receptor tyrosine-protein kinase erbB-2, CD340 or p185 is an enzyme that in humans is encoded by the ERBB2 gene. Over expression of this gene is correlated with higher aggressiveness in breast cancers...
protein levels in breast cancer cells, from 14% at 1.25 to 78% at 10 milligrams per liter, and targeting of fatty acid synthase
Fatty acid synthase
Fatty acid synthase is an enzyme that in humans is encoded by the FASN gene.Fatty acid synthase is a multi-enzyme protein that catalyzes fatty acid synthesis...
by related drugs has been suggested as a possible treatment. Antiproliferative and pro-apoptotic effects have been shown in colon cells as well. 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
Leptin
Leptin is a 16 kDa protein hormone that plays a key role in regulating energy intake and energy expenditure, including appetite and metabolism. It is one of the most important adipose derived hormones...
signaling. It is found naturally in the industrial strain Cephalosporium caerulens (Sarocladium oryzae
Sarocladium oryzae
Sarocladium oryzae is a plant pathogen causing the sheath rot disease of rice. In culture it produces 0.3–0.627 micrograms of helvolic acid and 0.9–4.8 micrograms of cerulenin per milliliter of culture medium. The level of helvolic acid correlated with a higher incidence of sheath rot...
, the sheath rot pathogen of rice).