Alongside this major metabolite, type B trichothecenes are among the most toxic
mycotoxin compounds and best-studied virulence factors. The mechanism of action
of this mycotoxin is based on the inhibition of protein synthesis in eukaryotes.
Trichothecenes interact with peptidyl transferase enzyme binding the 60S ribosomal
subunit, thus causing the inhibition of translation. Alternative mechanism of action
involves the activation of numerous mitogen-activated protein kinases (MAPKs)
[60]. Humans and animals that have consumed trichothecene mycotoxins present
various symptoms, such as vomiting, dizziness, diarrhea, and spontaneous abortion
[81]. Moreover, the potential of trichothecenes to act as virulence factors in plantfungal interactions and elicit plant defense responses has been investigated [82].
While trichothecene production is not required for Fusarium to develop on the host
and penetrate its tissues, they still are essential compounds for the exposure of the
pathogen after initial colonization [60, 83].
The trichothecene biosynthetic (TRI) gene cluster is responsible for trichothecene
biosynthesis and was first characterized in F. graminearum and F. sporotrichioides
[84–86]. Trichothecene biosynthetic enzymes and direct regulatory proteins
are encoded by 15 genes which are located at three different loci on different
chromosomes: a 12-gene core TRI cluster [80, 87]; the two-gene locus, TRI1
which encodes a cytochrome P450 monooxygenase and TRI16 which encodes an
acyl transferase; and a single acyl transferase gene TRI101 locus that is responsible
for esterification of acetate to the hydroxyl function at carbon atom 3 (C-3) of
trichothecenes [88]. In F. sporotrichioides, the TRI1 enzyme catalyzes the hydroxylation of trichothecenes at C-8, and the TRI16 enzyme catalyzes esterification of
a five-carbon carboxylic acid, isovalerate, to the C-8 oxygen [89, 90]. Analysis of the
TRI loci in 16 species of Fusarium exposed that TRI1 and TRI101 are in the core TRI
cluster in four species of Fusarium that are members of the F. incarnatum-equiseti
species complex [91, 92]. It was shown that TRI16 and TRI10 are major transcriptional regulators of TRI expression [93].
The trichothecenes have a skeleton resulting from the farnesyl pyrophosphate
(FPP) [94, 95]. The first step in the biosynthesis pathway is the conversion
of FPP to trichodiene. This reaction is governed by TRI5-encoded trichodiene
synthase [96]. Subsequently nine reactions follow, catalyzed by the enzymes
encoded by TRI4, TRI101, TRI11, and TRI3, correspondingly, and leading to the
formation of calonectrin [80]. All these steps are common for type A trichothecenes (T-2 toxin) and type B trichothecenes (NIV and DON) producing Fusaria
[76, 80].
A comparative study showed that similar genes are functioning in
F. graminearum and F. sporotrichioides [85]. For instance, TRI7 and TRI13 are
functional only in F. sporotrichioides and in F. cerealis as well as in the strains of
F. graminearum and F. culmorum producing NIV [86]. In F. graminearum DON
producers, FgTri7 and FgTri13 are not functioning [86]; therefore, the biosynthesis
continues directly from calonectrin with the products of FgTri1 and FgTri8 and leads
to the formation of either 3AcDON or 15AcDON followed by DON [97]. In
contrast, in NIV producers, the pathway proceeds with the product of FgTri1 to
generate 4AcNIV and the last step with FgTri8 product giving NIV [76]. Alexander
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Ł. Stępień et al.
mycotoxin compounds and best-studied virulence factors. The mechanism of action
of this mycotoxin is based on the inhibition of protein synthesis in eukaryotes.
Trichothecenes interact with peptidyl transferase enzyme binding the 60S ribosomal
subunit, thus causing the inhibition of translation. Alternative mechanism of action
involves the activation of numerous mitogen-activated protein kinases (MAPKs)
[60]. Humans and animals that have consumed trichothecene mycotoxins present
various symptoms, such as vomiting, dizziness, diarrhea, and spontaneous abortion
[81]. Moreover, the potential of trichothecenes to act as virulence factors in plantfungal interactions and elicit plant defense responses has been investigated [82].
While trichothecene production is not required for Fusarium to develop on the host
and penetrate its tissues, they still are essential compounds for the exposure of the
pathogen after initial colonization [60, 83].
The trichothecene biosynthetic (TRI) gene cluster is responsible for trichothecene
biosynthesis and was first characterized in F. graminearum and F. sporotrichioides
[84–86]. Trichothecene biosynthetic enzymes and direct regulatory proteins
are encoded by 15 genes which are located at three different loci on different
chromosomes: a 12-gene core TRI cluster [80, 87]; the two-gene locus, TRI1
which encodes a cytochrome P450 monooxygenase and TRI16 which encodes an
acyl transferase; and a single acyl transferase gene TRI101 locus that is responsible
for esterification of acetate to the hydroxyl function at carbon atom 3 (C-3) of
trichothecenes [88]. In F. sporotrichioides, the TRI1 enzyme catalyzes the hydroxylation of trichothecenes at C-8, and the TRI16 enzyme catalyzes esterification of
a five-carbon carboxylic acid, isovalerate, to the C-8 oxygen [89, 90]. Analysis of the
TRI loci in 16 species of Fusarium exposed that TRI1 and TRI101 are in the core TRI
cluster in four species of Fusarium that are members of the F. incarnatum-equiseti
species complex [91, 92]. It was shown that TRI16 and TRI10 are major transcriptional regulators of TRI expression [93].
The trichothecenes have a skeleton resulting from the farnesyl pyrophosphate
(FPP) [94, 95]. The first step in the biosynthesis pathway is the conversion
of FPP to trichodiene. This reaction is governed by TRI5-encoded trichodiene
synthase [96]. Subsequently nine reactions follow, catalyzed by the enzymes
encoded by TRI4, TRI101, TRI11, and TRI3, correspondingly, and leading to the
formation of calonectrin [80]. All these steps are common for type A trichothecenes (T-2 toxin) and type B trichothecenes (NIV and DON) producing Fusaria
[76, 80].
A comparative study showed that similar genes are functioning in
F. graminearum and F. sporotrichioides [85]. For instance, TRI7 and TRI13 are
functional only in F. sporotrichioides and in F. cerealis as well as in the strains of
F. graminearum and F. culmorum producing NIV [86]. In F. graminearum DON
producers, FgTri7 and FgTri13 are not functioning [86]; therefore, the biosynthesis
continues directly from calonectrin with the products of FgTri1 and FgTri8 and leads
to the formation of either 3AcDON or 15AcDON followed by DON [97]. In
contrast, in NIV producers, the pathway proceeds with the product of FgTri1 to
generate 4AcNIV and the last step with FgTri8 product giving NIV [76]. Alexander
220
Ł. Stępień et al.