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Secondary metabolites in general
Secondary metabolites are generally defined as
compounds that are not essential for growth or
survival of the producing organism, however
this is not true in all cases (pigments, sideophores
and pheromones). The production of these metabolites is tightly
regulated and dependent on the immediate environment and developmental
stage of the producing organism. The group includes
both simple molecules such as alcohols, sugars and organic acids; and
complex compounds such as polyketides, flavonoids, terpenes
and non-ribosomal peptide compounds (Medentsev & Akimenko 1998)
(KEGG).
Screening studies has revealed the huge functional
diversity of secondary metabolites, which includes functional classes
such as antibiotics, pigments (photoprotection), hormones/pheromones,
cytostatics, systemic toxins (phytotoxins,
fungicides, insecticides and immunosuppressives) and many others.
Screening has been the most
successful strategy for linking compounds with a given property, however
as this approach might
be ideal for identification of new compounds with
a specific function, it does not lead
to the identification of novel functional classes.
Beneficial functions for the producing
organism, includes virulence factors (eg.
trichothecenes) and siderophores involved in
Fe2+ uptake, but for the majority of the known secondary
metabolites, the allelotic effects on the ecological community the
producer inhabits, has not been studied (Medentsev & Akimenko 1998).
Secondary metabolites produced by Fusarium sp.
Chemical
analysis has shown that Fusarium sp. are capable of producing a
wide range of secondary metabolites, including zearalenone (ZON),
fumonisin (B1, B2, B3, B4), trichothecenes
(T-2 toxin, deoxynivalenol (DON/vormitoxin), nivalenol (NIV) and
diacetoxyscirpenol (DAS)),
moniliformin, enniatin,
fusaric acid, fusarin C, fusaproliferin,
aurofusarin, fuscofusarin and their respectable derivates (Medentsev &
Akimenko 1998), (Desjardins 2003).
The T-2 toxin is the most potent of the identified
metabolites, with respect to toxicity. Cereal
grains infected with F. sporotrichioides
and F. poae (producers of T-2 toxin) caused thousands of deaths
in Russia during the great famines (1932-34 and 1952-1955) and
the second World War.
As people were forced
to gather and eat old grains
left in the field over the winter, wich
resulted in many cases of deadly alimentary toxic
aleukia (ATA) (Nelson et al. 1994).
Use of F. graminearum infected wheat, barley,
oats, rye and rice as
food or feed typically results in vomiting, headache, diarrhea,
abdominal pain, chills, giddiness, convulsions, loss of appetite and nausea. The
observed symptoms are thought to be the result of a synergistic effect
of the secondary metabolites trichothecenes (T-2 toxin, DON, NIV),
fusarenon-X, diacetoxyscirpenol and neosolaniol (Marasas et al.
1984).
The toxins also affect livestock (Table 1). Pigs fed
with F. poae
and F. sporotrichioides infected grain, with zearalenone
concentrations above 5
ppm, display “Estrogenic syndrome” with feminization of boars,
reduced litter size and weak piglets (Department of crop sciences
University of Illinois 1997). While low concentrations of deoxynivalenol
(DON) produced by F. graminearum can lead
to “Feed refusal” and “Emetic syndromes” in swine (Forsyth et al.
1977). F. moniliforme typically contaminate grain with fumonisin
B1 and B2, and feeding of horses with such material can lead to Equine
Leukoencephalomalacia (liquefactive necrosis
of the white brain matter) and Pulmonary
syndrome in swine (Marasas et al. 1988).
The polyketide aurofusarin produced by F.
graminearum, F. pseudograminearum, F. culmorum, F. acuminatum, F.
avenaceum, F. crookwellens, F. poae, F. sambucinum, F. sporotrichioides
and F. tricinctum has been shown to
affect the vitamin E concentration and fatty acid composition of egg
yolks from Japanese quails (Dvorska 2001).
|
Affects
|
Toxin |
Produced by |
Disease/syndrome |
|
Humans
|
T-2 toxin
unidentified
mycotoxin
Synergistic
effect |
F.
Sporotrichioides, F. poae
F. poae
F.
graminearum |
Alimentary
toxic aleukia (ATA) (d)
Kashin-Beck
disease (e)
(c) |
|
Cattle |
Furanoterpenoide
T-2 toxin |
F. solani
F.
Sporotrichioides, F. poae |
Mouldy sweet
potato toxicosis (d)
Hemorrhagic
syndrome (d) |
|
Swine |
Zearalenone
DON
Fumonisin B1,
B2
T-2 toxin |
F. poae, F.
sporotrichioides
F.
graminearum
F.
moniliforme
F.
Sporotrichioides, F. poae |
Estrogenic
syndrome (a)
Feed refusal
and Emetic syndromes (b)
Pulmonary
syndrome (c)
Hemorrhagic
syndrome (d) |
|
Poultry |
Aurofusarin
|
F.
graminearum,
F. culmorum
|
Altered fatty acid composition in
egg yolks (g) |
|
Horses
|
Fumonisin B1,
B2 |
F.
moniliforme |
Equine
Leukoencephalomalacia (c) |
|
Water buffalo |
na |
F. equiseti |
Degnala
disease (d) |
Table 1
Diseases in humans and livestock caused by secondary metabolites
produced by Fusarium sp.. (a) (Department of crop sciences
University of Illinois at Urbana-Champaign August 1997), (b) (Forsyth
et al. 1977), (c) (Marasas et al. 1988), (d) (Nelson et
al. 1994), (e) (Chasseur et al. 2001) and (g) (Dvorska et al
2003).
The sequencing of several
Fusarium genomes in recent years has revealed that their
biosynthetic potential, based on the number of PKS, NRPS and terpene
cyclases, must be far greater than previously
believed based on metabolism studies. A possible
explanation for this could be that many of the involved genes are only
expressed under very specific conditions (environmental and
developmental) which are not met by the normal incubation and media
conditions used for most metabolomics studies. Another possibility is
that the compounds are only produced in very small amounts
making them undetectable, due to masking by other metabolites.
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