Cerulenin is an antifungal antibiotic that inhibits

fatty acid In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, ...

and steroid biosynthesis. 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 iden ...

, 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 AMPK may refer to: * AMP-activated protein kinase 5' AMP-activated protein kinase or AMPK or 5' adenosine monophosphate-activated protein kinase is an enzyme (EC 2.7.11.31) that plays a role in cellular energy homeostasis, largely to activate gl ...

, in the

hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...

. 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 fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have b ...

'' 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 in humans is encoded by the ''ERBB2'' gene. ERBB is abbreviated from erythroblastic oncogene B, a gene originally isolated from the avian genome. The human protein is also frequently refer ...

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 grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes ( morphology) and death. These changes incl ...

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 mesothel ...

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 ''Sarocladium oryzae'' (Sawada) is a plant pathogen causing the sheath rot disease of rice and bamboo blight in Asia. Taxonomy and morphology ''Sarocladium oryzae'' has irregularly penicillate conidiophores and slimy, 1-celled conidia. ''Sa ...

'', the sheath rot pathogen of rice).

References

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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