Sphingosine Analogs: an Emerging New Class of Toxins that Includes the Fumonisins

Abstract

There is an emerging new class of toxins - the sphingosine analog toxins. First to be identified were the AAL toxins, host-specific toxins produced by the fungus Alternaria alternata f. sp. lycopersici to facilitate invasion of tissues in susceptible plants. The best studied members of the class are the fumonisins, which were initially isolated as tumor promoters from corn infested with Fusarium moniliforme, the major ear rot fungus of corn and an important pathogen of stored grains worldwide. Recently, the sphingosine analog toxins penaresidins A and B and penazetidine A have been isolated from marine sponges of the Penares genus. All these toxins are long-chain fatty amines with free amino groups. The mycotoxins are characterized by the absence of a C-1 hydroxyl group and the presence of one or more propanetricarboxylic acid esters, whereas the sponge toxins are characterized by a four-membered azetidine ring. The observation that removing propanetricarboxylic acid moieties from fumonisins by alkaline hydrolysis yields fragments that have half the molecular weight but retain comparable cytotoxic activity over a broader spectrum of mammalian cell lines has prompted the suggestion that metabolism by non-specific carboxylesterases may be a required initial step in their toxic mechanism. Toxins in this new class presumably act as either agonists, antagonists or synthesis inhibitors of sphingosine, which is becoming recognized as an important intracellular regulatory molecule. These toxins may prove useful as experimental tools to explore the regulatory roles of sphingosine.