Submitted to: Methods in Enzymology
Publication Type: Book / Chapter
Publication Acceptance Date: July 1, 1999
Publication Date: December 15, 1999
Interpretive Summary: This paper describes a method for making a fungal chemical, called ISP-I. It is needed to study the function of a poorly understood group of fats. In animals and plants there is a group of fats called sphingolipids. The "sphin" in sphingolipid is derived from the word "sphinx", a mythical creature that posed riddles to all that met it. This name was chosen because the function of these fats was a mystery. In cells, the sphingolipids are produced in a series of steps that are known collectively as de novo sphingolipid biosynthesis. This pathway produces over 300 distinctly different sphingolipids. There are several diseases that are caused by genetic defects in the production and destruction of sphingolipids. Very little is known about the role of sphingolipids in how normal cells function. In 1991, a naturally occurring chemical that blocked the de novo biosynthesis of sphingolipids was reported. It was called fumonisin and it was produced by molds that occur on corn. This mold was associated with animal and plant diseases and sometime later it was shown that the fumonisin could also cause the same diseases in animals. Not long after the discovery that fumonisin blocked a step in sphingolipid biosynthesis, another class of fungal chemicals was discovered that blocked a different step in sphingolipid biosynthesis. One of the first discovered was ISP-I. When both fungal chemicals were given to cells, the ability of the fumonisin to kill the cells was prevented. The reason for this is that the fumonisin causes a large increase in a sphingolipid that poisons cells and the new class of fungal chemicals prevented this increase. These two new classes of compounds are proving to be very useful in solving the mystery of the sphingolipids and is the subject of this paper.
Technical Abstract: No abstract for book chapter. Chapter Title: "Fermentation, partial purification, and use of serine palmitoyltransferase inhibitors" IN: Methods of Enzymology, Merrill, Jr., A.H. and Hannun, Y.A., Eds., Academic Press, Inc., Orlando, FL.