Fumonisin structure

Fusarium moniliforme sya verticillioides causes the so-called ear rot disease in maize and produces fumonisin B, (IB,), one of the most frequently detected mycotoxins in the food supply chain worldwide (Steyn, 1995). FBi can inhibit lipid formation, particularly in the liver. Fumonisins have been detected and investigated only relatively recently. Several structurally related forms of fumonisins (FBS) have been associated with human cancer (e.g. FB with oesophageal cancer) as well as with a host of problems in livestock fed with FB -contaminated feed (D Mello, 2003 Benbrook, 2005). 

Figure 9.3 Chemical structures of (a) thichothecenes (including deoxynivalenol and T-2 toxin), (b) zearalenone, and (c) fumonisin BL...

Fumonisins, first isolated from corn cultures of Fusarium moniliforme, are also produced by several other Fusarium species (F. anthophilum, F. proliferatum, F. dlamini, F. napiforme, and F. nygamai) (68). From the seven structurally related fumonisin analogs, only fuminisins B, (FB,), B2 (FB2), and B3 (FB3) are naturally occurring in com (69,70). The first two invariably occur together and have been extensively studied. Molecular structures of fumonisins are shown in Fig. 8. 

Tanaka, T., Abbas, H. K., and Duke, S. O. 1993. Structure-dependent phytotoxicity of fumonisins and related compounds in a duckweed bioassay. Phytochemistry 33, 779-785... 

The chemical structure of fumonisin (Fig. 5.IB) is remarkably similar to that of the sphingoid bases sphinganine (Sa) and sphingosine (So), and fumonisin has been shown to inhibit the enzyme ceramide synthase in de novo sphingolipid metabolism (Wang et al., 1991). Ceramide synthase... 

Humpf, H. U. and Voss, K. A. (2004). Effects of thermal food processing on the chemical structure and toxicity of fumonisin mycotoxins. Mol. Nutr. Food Res. 48(4), 255-269. 

Inhibition of ceramide synthase could cause symptoms by depletion of ceramide and ceramide derivatives or by toxic increases in sphinganine and its derivatives. The effects of these phytotoxins are so rapid, that it is unlikely that depletion of ceramides is responsible for cellular death. Others have invoked induction of apoptosis in the mode of action of these compounds [e.g., 6] however, treatment of plant tissues with phytoshingosine and sphinganine causes symptoms very similar to those caused by inhibition of ceramide synthase [7]. Very low levels of AAL-toxin tuid other ceramide synthase inhibitiors may cause apoptosis, but the rapidity of plasma membrtme damage at one micromolar and higher concentrations makes it unlikely that it is involved in the main phytotoxic effect. Attempts have been made to find a ceramide synthase inhibitor with good phytotoxicity, but little mammalitm toxicity [e.g., 8]. However, even inhibitors with little structural similarity to the fumonisins such as australifimgin [9], have relatively little difference between mammalian and plant toxicity. Nevertheless, these studies demonstrate that the ceramide synthase pathway is a viable site for herbicides, provided an inhibitor can be found that is plant specific. This topic is considered in more detail in a recent review [10]. 

Fumonisins are a group of toxins produced primarily by Fusarium verticil-lioides (formerly called F moniliforme), Eprolifemtum and other related species which readily colonize corn all over the world [120-124]. Nine structurally related fumonisins including Bj, B2, B3, B4, A, and A2, have been described (fig. 8). Chemically, fiimonisin Bj is a derivative (diester) of propane-1,2,3-tricarboxylic acid of 2-amino-12,16-dimethyl-3,5,10,14,15-pentahydroxy-icosane [121-130]. The other fumonisins lack the tricarballylic acid or other ester groups [121, 131, 132]. Fumonisins are chemically similar in structure to toxins (AAL) produced by Altemaria altemata [133]. Production of fumonisins hy Altermria has also been reported [134,135], and some fumonisin-producing Fusaria have been knovm to produce AAL toxins [136]. 

Fig. 8. Chemical structures of different classes of fumomsins. The R residue is 3-hydroxypyridmium in fumonisins P1-P3 while the others are tricarballyl esters. 

Gelderblom WCA, Cawood ME, Snyman SD, Marasas WFO Structure-activity relationships of fumonisins in short-term carcinogenesis and cytotoxicity assays. Food Chem Toxicol 1993 31 407-414. 

Representative Compounds Aflatoxins Citrinin Ergot alkaloids Fumonisins Ochratoxin A Patulin Trichothecenes Zearalenone Stachybotrys toxin Chemical Formula C17H12O6 (Aflatoxin Bi) Chemical Structure Aflatoxin Bi... 

Fumonisin B, (Fig. 9.9) is the major fumonisin metabolite produced by the fungus, Fusarium moniliforme. The metabolite has been implicated as a carcinogen in animals (Holcomb et al., 1993). The structure is shown in Figure... 

Another group of toxins called the AAL-toxins was fotmd to have a structural relationship to the fumonisins, since they have only one tricarboxylic acid (TCA) moiety. AAL-toxin TAi (265) and TA2 (266) (Fig. 5.2) are produced by the fungus Alternaria alternata f. sp. lycopersici and can lead to phytotoxic effects on several crops such as tomatoes and weeds (200). Due to the toxic effects of long alkyl-chain pyridinium compounds, this new class of fumonisins is of high interest (201). 

Toxicity of fumonisins is caused by inhibition of the enzyme sphingosine N-acetyltransferase (ceramide synthase) due to the structural similarity of fumonisins with sphingosine (see Section 3.5.1.1.3). The toxic effects are closely related to the presence of the amino group in the molecule of fumonisin the reaction products with reducing sugars are virtually non-toxic as the amino group is blocked. Fumonisin B2 is more cytotoxic than fumonisin Bp... 

The pattern of heptacellular damage describe is typical ofaflatoxin, including the distinct centrilobular pattern and the bile duct hyperplasia. Fumonisins are also hepatotoxic mycotoxins, but liver damage from fumonisins is typically mild to moderate and characterized by a more disorganized hepatic structure and little or no evidence of bile duct hyperplasia. 

The ceramide synthase pathway is clearly a viable site for herbicides, provided an inhibitor can be found that is plant specific. We have been unsuccessfiil in finding a ceramide synthase inhibitor with high phytotoxicity, but low mammalian toxicity (e.g., 11). Even inhibitors widi little structural similarity to the fumonisins, such as australifungin 12), have relatively little difference between mammalian and plant toxicity. This topic is considered in more detail in a recent review 13). 

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