Cerulenin is an

antifungal An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as ...

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

that inhibits

fatty acid In chemistry, in particular in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated and unsaturated compounds#Organic chemistry, saturated or unsaturated. Most naturally occurring fatty acids have an ...

and

steroid biosynthesis A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes t ...

. It was the first natural product antibiotic known to inhibit lipid synthesis. 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 (FAS) 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. It is not a single enzyme but a whole enzymatic system composed of two ide ...

, blocking the interaction of

malonyl-CoA Malonyl-CoA is a coenzyme A derivative of malonic acid. Biosynthesis Malonyl-CoA cannot cross membranes and there is no known malonyl-CoA import mechanism. The biosynthesis therefore takes place locally: * cytosol: Malonyl-CoA is formed by c ...

. 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 The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...

. 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'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungal microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have be ...

'' 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 Receptor tyrosine-protein kinase erbB-2 is a protein that normally resides in the membranes of cells and is encoded by the ''ERBB2'' gene. ERBB is abbreviated from erythroblastic oncogene B, a gene originally isolated from the avian genome. The ...

protein levels in breast cancer cells, from 14% at 1.25 to 78% at 10 milligrams per liter, and targeting of

by related drugs has been suggested as a possible treatment. Antiproliferative and pro-

apoptotic Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemical events lead to characteristic cell changes ( morphology) and death. These ...

effects have been shown in colon cells as well. At an

intraperitoneal The peritoneum is the serous membrane forming the lining of the abdominal cavity or coelom in amniotes and some invertebrates, such as annelids. It covers most of the intra-abdominal (or coelomic) organs, and is composed of a layer of mesothe ...

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 (from Ancient Greek, Greek λεπτός ''leptos'', "thin" or "light" or "small"), also known as obese protein, is a protein hormone predominantly made by adipocytes (cells of adipose tissue). Its primary role is likely to regulate long ...

signaling. It is found naturally in the industrial strain ''Cephalosporium caerulens'' (''

Sarocladium oryzae ''Sarocladium oryzae'' (Sawada) is a plant pathogen causing the of rice and of Bambusoideae spp. in Asia. Taxonomy and morphology ''Sarocladium oryzae'' has conidiophores which are irregularly penicillate and slimy, 1-celled conidia. It wa ...

'', the sheath rot pathogen of rice).

References

{{Reflist

External links

Cerulenin from

Fermentek Fermentek Ltd. is a biotechnological company in the Atarot industrial zone of Jerusalem, Israel. It specializes in the research, development and manufacture of biologically active, natural products isolated from microorganisms as well as from ot ...

Antifungals Carboxamides Ketones Alkene derivatives Epoxides

See also

References

External links