Biomedical Engineering Reference
In-Depth Information
Fumonisins
Another important group of
Fusarium
mycotoxins are the fumonisins,
produced mainly by
F. verticillioides, F. proliferatum, F. subglutinans
and
F. nygamai
(Bennett and Klich 2003). They affect animals by interfering
with their sphingolipid metabolism (Merrill et al. 2001). Besides various
animal diseases they are suspected to be responsible for certain forms
of human esophageal cancer observed in Transkai (South Africa), China
and Northeast Italy (Peraica et al. 1999). Moreover, fumonisin B1 has
been associated with neural tube defects in experimental animals and
may therefore be involved in cases of spinal bifi da in humans (Hendricks
1999). The toxin has been assigned a 2B carcinogen (probably carcinogenic
to humans) status by the International Research Agency for Cancer
(IARC 1993, Rheeder et al. 2002). As in other mycotoxin producers, genes
are organized in clusters within the genome. Corn is the major commodity
affected by this group of toxins although some occurrence has been found
in sorghum and rice (CAST 2003). A major disease of horses that includes
a softening of the white matter in the brains (leukoencephalomalacia)
is caused by the fumonisins (Marasas et al. 1988). Swine lung edema
is also produced by the fumonisins (Colvin and Harrison 1992). The
fumonisins are suspect in the cause of esophageal tumors in certain human
populations (Marasas 1993 and 1996). Regardless of the effects on animals,
the fumonisins are often involved in liver toxicity and their major mode
of action is that they interfere with sphingolipid metabolism. There is no
carryover of fumonisins into milk in cattle and there appears to be little
absorption of them in tissues (Richard et al. 1996). Because of the lack of
toxicity information due to fumonisins in some animal species, disease
diagnosis can be diffi cult.
Fumonisins are believed to be synthesized through the condensation
of the amino acid alanine to an acetate-derived precursor (Branham and
Plattner 1993). Branched-chain methyl groups are added at C-12 and C-16
by an S-adenosyl methionine transferase. The order and number of the
subsequent steps in the biosynthetic pathway involved in the oxygenation
and subsequent esterifi cation of the acetate-derived backbone are as yet
unknown. However if Fumonisin biosynthesis is similar to the synthesis of
afl atoxins and trichothecenes, less oxygenated homologues, such as FB2, FB3
and FB4 are likely precursors of the most highly oxygenated homologue,
FB1 (Desjardins et al. 1996). It is still not clear however whether oxygenation
and methylation occur before or after condensation with alanine.
Identifi cation of the
fum
gene cluster (Fig. 5) allowed for the formulation
of a biosynthetic model (Fig. 6) which also offered an explanation for
