is catalyzed by Fum13p [114], fumonisin C-10 hydroxylation is most likely catalyzed by Fum2p [2], and esterification of the tricarballylic moieties to the hydroxyls
at C-14 and C-15 of fumonisins is catalyzed by Fum14p [115]. Although Fum14p
catalyzes the C-14/C-15 esterification, analysis of gene deletion mutants indicated
that Fum7p, Fum10p, and Fum11p also contribute to the formation of the tricarballylic esters [116]. The final step in the fumonisin biosynthesis is the Fum3pcatalyzed hydroxylation of the fumonisin backbone at the C-5. Fum3p is predicted
to encode a dioxygenase, and its role in fumonisin biosynthesis was confirmed using
enzyme assay in which the purified protein catalyzed the C-5 hydroxylation [117].
Phylogenetic discord of the FUM gene-based and primary metabolism gene
genealogies was demonstrated, and it coincides with the differences in the FUM
cluster genomic context, whereas it was not compatible with fumonisin chemotype
differences [59]. Proctor et al. (2013) proposed that combination of a variety of
dynamic processes, such as cluster duplication and loss, balancing selection, shifts in
functional contrast, translation, and horizontal transfers, has shaped the evolution
and distribution of some secondary metabolite biosynthetic gene cluster, as well as
contributed to the metabolic diversity in fungi [59, 87, 118–121].
5.1.3 Zearalenone
Zearalenone (ZEA) is a phenolic resorcylic acid lactone mycotoxin with low acute
toxicity that does not cause fatal toxicosis. It is associated mainly with maize but also
occur in wheat, barley, and sorghum. Moreover, it can cause reproductive problems
in farm animals, particularly in pigs. Zearalenone was first purified from a culture
of F. graminearum and originally was designated as fermentation estrogenic substance F-2. Then, it was structurally characterized and named zearalenone [122].
ZEA is produced by several Fusarium species that usually also produce type B
trichothecenes, and therefore it is found together with DON and NIV. Fungi belonging to the F. graminearum species complex are the most significant ZEA producers;
however, there are other species that have been reported to produce ZEA, such as F.
culmorum [123] and F. cerealis [124]. Fungi from the F. oxysporum, F. solani, and F.
fujikuroi species complexes are not able to produce ZEA [1]. F. equiseti-incarnatum
species complex is an exception here, as these fungi are able to produce ZEA but
produce type A trichothecenes instead of type B [45, 125].
ZEA may undergo various modifications in the organisms of plants, fungi, and
animals by phase I and phase II metabolism. Modified forms of ZEA found in animal
feed include its reduced phase I metabolites (e.g., α-zearalenol, β-zearalenol,
α-zearalanol, β-zearalanol) and its phase II conjugate forms with glucose, sulfate,
and/or glucuronic acid [60]. Early chemical studies have proposed that ZEA is
derived from the acetate through the polyketide synthesis pathway [126]. More recent
research contributed to the development of the zearalenone biosynthetic gene cluster
with two polyketide synthases, PKS4 and PKS13, which have been characterized later
[123, 127]. Despite the fact that biological functions of these genes have still been
relatively poorly understood and some strains do not produce ZEA while still carry
at least one of the genes, some evidence has been reported that the PKS genes
10 Fusarium Secondary Metabolism Biosynthetic Pathways: So Close but So. . .
223
at C-14 and C-15 of fumonisins is catalyzed by Fum14p [115]. Although Fum14p
catalyzes the C-14/C-15 esterification, analysis of gene deletion mutants indicated
that Fum7p, Fum10p, and Fum11p also contribute to the formation of the tricarballylic esters [116]. The final step in the fumonisin biosynthesis is the Fum3pcatalyzed hydroxylation of the fumonisin backbone at the C-5. Fum3p is predicted
to encode a dioxygenase, and its role in fumonisin biosynthesis was confirmed using
enzyme assay in which the purified protein catalyzed the C-5 hydroxylation [117].
Phylogenetic discord of the FUM gene-based and primary metabolism gene
genealogies was demonstrated, and it coincides with the differences in the FUM
cluster genomic context, whereas it was not compatible with fumonisin chemotype
differences [59]. Proctor et al. (2013) proposed that combination of a variety of
dynamic processes, such as cluster duplication and loss, balancing selection, shifts in
functional contrast, translation, and horizontal transfers, has shaped the evolution
and distribution of some secondary metabolite biosynthetic gene cluster, as well as
contributed to the metabolic diversity in fungi [59, 87, 118–121].
5.1.3 Zearalenone
Zearalenone (ZEA) is a phenolic resorcylic acid lactone mycotoxin with low acute
toxicity that does not cause fatal toxicosis. It is associated mainly with maize but also
occur in wheat, barley, and sorghum. Moreover, it can cause reproductive problems
in farm animals, particularly in pigs. Zearalenone was first purified from a culture
of F. graminearum and originally was designated as fermentation estrogenic substance F-2. Then, it was structurally characterized and named zearalenone [122].
ZEA is produced by several Fusarium species that usually also produce type B
trichothecenes, and therefore it is found together with DON and NIV. Fungi belonging to the F. graminearum species complex are the most significant ZEA producers;
however, there are other species that have been reported to produce ZEA, such as F.
culmorum [123] and F. cerealis [124]. Fungi from the F. oxysporum, F. solani, and F.
fujikuroi species complexes are not able to produce ZEA [1]. F. equiseti-incarnatum
species complex is an exception here, as these fungi are able to produce ZEA but
produce type A trichothecenes instead of type B [45, 125].
ZEA may undergo various modifications in the organisms of plants, fungi, and
animals by phase I and phase II metabolism. Modified forms of ZEA found in animal
feed include its reduced phase I metabolites (e.g., α-zearalenol, β-zearalenol,
α-zearalanol, β-zearalanol) and its phase II conjugate forms with glucose, sulfate,
and/or glucuronic acid [60]. Early chemical studies have proposed that ZEA is
derived from the acetate through the polyketide synthesis pathway [126]. More recent
research contributed to the development of the zearalenone biosynthetic gene cluster
with two polyketide synthases, PKS4 and PKS13, which have been characterized later
[123, 127]. Despite the fact that biological functions of these genes have still been
relatively poorly understood and some strains do not produce ZEA while still carry
at least one of the genes, some evidence has been reported that the PKS genes
10 Fusarium Secondary Metabolism Biosynthetic Pathways: So Close but So. . .
223