Brefeldin A is a lactone antiviral produced by the fungus Penicillium brefeldianum. Brefeldin A inhibits protein transport from the endoplasmic reticulum to the golgi complex indirectly by preventing association of COP-I coat to the Golgi membrane. Brefeldin A was initially isolated with hopes to become an antiviral drug but is now primarily used in research to study protein transport.
History
The compound gets its name from a species of anamorph fungus of the Penicillium genus known as Eupenicillium brefeldianum, though it is found in a variety of species that span several genera. It was first isolated from Penicillium decumbens in 1958 by V.L. Singleton who initially called it Decumbin. It was later identified as a metabolite by H.P. Siggs who then went on to identify the chemical structure of the compound in 1971. It is poorly soluble in water (slightly miscible). GBF1 is a member of the Arf family of GEFs which are recruited to membranes of the Golgi. It is responsible for the regulation of Arf1p GTPase. SNARE proteins mediate membrane fusion and it is postulated that the described SNARE build up in the Golgi increases the chances of aberrant fusion of the Golgi membrane with that of the ER. which can result in apoptosis.
Toxicity
The toxological effects of brefeldin A have not been studied extensively yet. Some animal LD<sub>50</sub> values have been reported including 250 mg/kg in mice (interperitoneal) and 275 mg/kg in rats (oral). Some macrolides have been shown to produce allergic reactions and though uncommon this possibility in the case of brefeldin A cannot be disregarded as of yet.