Page Banner

United States Department of Agriculture

Agricultural Research Service

Title: Fungal Inhibitors of Sphingolipid Biosynthesis: Tools, Toxins, and Therapeutic Agents

Authors
item Riley, Ronald
item Norred, William
item Voss, Kenneth

Submitted to: Mycotoxins
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 21, 1999
Publication Date: July 1, 1999

Interpretive Summary: Without a doubt, the known biological diversity of the fungi is accompanied by an even greater chemical diversity. This is certainly good news given the past successes and future hope for the discovery of new fungal metabolites to serve mankind. However, the same fungi that have served so well as chemical factories for producing useful drugs and research tools are frequently contaminants of the food we eat and the air we breathe and thus are potential agents of disease. In this sense, fungal chemicals are potentially like a triple edged sword, capable of cutting in three directions; as research tools for the biochemist, poisons to plants and animals, and drugs for the treatment of diseases. RRC scientists are reviewing these complex associations of fungi with humankind. An example of fungal chemicals as tools, toxins, and therapeutic agents, are the recently discovered fungal chemicals that block the synthesis of a unique group of fats called sphingolipids. The first reported fungal chemical that blocked a cell's ability to make these unusual fats was a fungal chemical that is commonly found in corn, called fumonisin B1. Since this discovery in 1991, 40 known or suspected microbial chemicals have been found that block three different steps in the pathway for making sphingolipids. Most of these chemicals are made by fungi. These include fungal chemicals that block the first step, a step midway in the pathway and a step at the end of the pathway. The consequences of the blockage of the pathway are quite varied. In all cases the results reveal new information that is useful for understanding the importance of sphingolipids in cells.

Technical Abstract: It has been estimated that the total number of existing fungal species is 1.5 million. Even if overestimated, the total number of fungal species is quite large. Without a doubt, the known biological diversity of the fungi is accompanied by an even greater chemical diversity. This is certainly good news given the past successes and future hope for the discovery of new wfungal metabolites to serve mankind. However, the same fungi that have served so well as chemical factories for producing useful drugs and research tools, are frequently contaminants of the food we eat and the air we breath and thus are potential agents of disease. In this sense, fungal metabolites are potentially like a triple edged sword, capable of cutting in three directions; as research tools for the biochemist, poisons to plants and animals, and drugs for the treatment of diseases. Good examples of fungal metabolites as tools, toxins, and therapeutic agents, are the recently discovered inhibitors of de novo sphingolipid biosynthesis. The first reported fungal inhibitor of de novo sphingolipid biosynthesis was fumonisin B1. Since this discovery in 1991, 40 known or suspected microbial inhibitors of de novo sphingolipid biosynthesis, most of which are derived from fungi, have been found. These include metabolites that inhibit serine palmitoyltransferase, ceramide synthase (including fumonisin B1), and several recently discovered inhibitors of inositol phosphoceramide synthase.

Last Modified: 8/30/2014