Introduction to Fungi, Third Edition

EUROTIALES
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has similarities to the synthesis of fatty acids
from acetyl-CoA. Synthesis proceeds in cycles,
with one addition in each cycle which is followed
by modification of the side chain (initially a keto
group). Many other mycotoxins arising from
diverse biochemical pathways are produced
by Aspergillus and Penicillium, and an excellent
introduction to the biochemical diversity of
mycotoxins has been given by Moss (1994).
Good reviews of ecological aspects and health
implications of these mycotoxins have been
written by Scudamore (1994), Bhatnagar et al.
(2002) and Pitt (2002). The ability to produce
mycotoxins such as aflatoxin, ochratoxin or
patulin is found in diverse groups of Aspergillus
and Penicillium. Since all or most of the genes
involved in the biosynthesis of a given mycotoxin
tend to be clustered in the genome, it is possible
that sporadic horizontal gene transfer has
occurred between different species, thus explaining
the lack of correlation between mycotoxin
production and phylogenetic placement (Varga
et al., 2003).
Aflatoxins
These polyketide-type metabolites are produced
by strains of Aspergillus flavus but not, apparently,
by the closely related A. oryzae (Bayman &
Cotty, 1993). The most common is aflatoxin B 1
(Fig. 11.14c), which is so named because it
fluoresces blue on a thin-layer chromatography
plate under UV light (aflatoxins G fluoresce
blue green). The fluorescence of aflatoxins is
so strong that heavily contaminated food
samples, e.g. the kernels of Brazil nuts, will
fluoresce under UV light. Aflatoxin B 1 is one of
the most potent carcinogens known, being
capable of inducing liver cancer at concentrations
below 1 mgkg 1 body weight (Cotty et al.,
1994). Consequently, stringent regulations
concerning maximum permissible aflatoxin
levels are in place in many countries. However,
these toxins may still present a health hazard
to consumers, and also to agricultural workers
because spores of A. flavus contain such high
toxin levels that their inhalation may pose a risk
of liver cancer (Olsen et al., 1988). Although the
crop may well become contaminated on the field,
A. flavus infections become visible only during the
storage of agricultural produce. Since the fungus
is xerophilic, it can colonize even dry products
(Lacey, 1994). Nuts, peanuts and spices are
particularly susceptible, but almost any food
can be contaminated. An infamous outbreak
of aflatoxicosis, turkey-X disease, occurred in
the UK in 1960 when about 100 000 turkeys
were killed by contaminated groundnut meal.
Further, cows eating contaminated feed will
produce milk containing the slightly modified
aflatoxins M (Scudamore, 1994). Because of their
ubiquity and extreme toxicity, aflatoxins must
be considered the most important food-borne
mycotoxins worldwide. The biosynthetic pathways
of aflatoxins are well characterized (Klich &
Cleveland, 2000). The mycotoxin sterigmatocystin,
produced by various Aspergillus spp., is a
precursor of aflatoxin and is also carcinogenic,
although it is comparatively rare in food and
feed (Moss, 1994). The production of secondary
metabolites usually occurs only when vegetative
growth has ceased and when conidium formation
ensues; the regulatory mechanisms coupling
conidiation with secondary metabolism are
beginning to be unravelled for A. nidulans
(Adams & Yu, 1998).
Ochratoxin A
This is a pentaketide/amino acid hybrid molecule
(Fig. 11.14d) which is produced by numerous
species of Aspergillus and Penicillium, especially
P. verrucosum, which is common on cereals in
temperate climates, and A. ochraceus and
A. carbonarius, which grow on the flesh of coffee
berries during drying. Coffee can, therefore, be
contaminated with ochratoxin A, but mercifully
much of it is destroyed during roasting (Viani,
2002). Ochratoxin A consumed with contaminated
cereals or meat has a long residence
time (half-life 35 days) in the human body.
It is highly nephrotoxic and has been implicated
in a degenerative human kidney disorder
called ‘Balkan endemic nephropathy’; it is also
strongly suspected to cause cancer of the gall
bladder (Stoev, 1998; O’Brien & Dietrich, 2005).
Further, ochratoxin A causes a renal degenerative
disorder of farm animals, especially pigs. A
chemically closely related mycotoxin is citrinin.