a molecular mass of about 351 kD [159]. Similar to enniatin biosynthesis,
beauvericin is also produced by a thiol template mechanism [160, 161]. However,
the two depsipeptide synthetases differ in their substrate selectiveness. Beauvericin
synthetase preferably accepts N-methyl-L-phenylalanine and some other aliphatic
hydrophobic amino acids. The efficiency of incorporation into the cyclodepsipeptide
framework decreases with the length of the side chain: N-methyl-L-phenylalanine
was easily replaced by ortho-, meta-, and para-fluoro-substituted phenylalanine
derivatives, as well as by N-methyl-L-leucine, N-methyl-L-norleucine, and
N-methyl-L-isoleucine residues [149]. Consequently, significant sequence homologies to some of the Fusarium enzymes were found [150], establishing a common
genetic background to depsipeptide biosynthesis. Previously, some Fusarium
species like Fusarium poae have been reported to produce ENNs and BEA simultaneously [162, 163], which is justified by the fact that both mycotoxins share
a common metabolic pathway and the co-occurrence of ENNs and BEA in field
samples infected by Fusarium spp. has been observed [164, 165]. Previous works
demonstrate high probability that even a single PCR-based esyn1-specific marker
can detect potential producers of both toxins among Fusarium isolates originating
from contaminated plant material [130, 163].
5.1.5 Fusaric Acid
Fusaric acid (FA) is a picolinic acid derivative which was isolated for the first time
from Fusarium heterosporum strains. Further research have proven that other
Fusarium species, e.g., F. verticillioides, F. fujikuroi, and F. oxysporum, are also
able to produce this mycotoxin [166, 167]. FA shows moderate impact on mammalian health, but its high toxicity to plants is documented. It is responsible for
“fusarium wilt” development through the lipid peroxidation, increase of reactive
oxygen species, and, finally, host cells’ death [168]. FA also causes bakanae disease
in rice seedlings and has a strong antimicrobial activity, inhibiting quorum sensing in
Gram-negative bacteria [169, 170].
Biosynthetic pathway of fusaric acid remains largely unexplored; however, the
gene cluster responsible for encoding of proteins involved in this process has been
identified in F. verticillioides. Initially, only 5 genes were described in fusaric acid
biosynthetic (FUB) gene cluster, but just a few years later, additional 7 contiguous
genes were located 14.6 kb upstream of the previous five genes identified [171, 172].
These genes are conserved in genomes of all FA-producing Fusarium strains, and no
significant differences in cluster organization between the species have been found
[167]. Functions of all 12 FUB genes were predicted using BLAST analysis (Table 2)
[172, 173].
Fusaric acid synthase encoded by FUB1 is responsible for the synthesis of sixcarbon polyketide chain using three acetyl-CoA molecules. Fusion of polyketide
chain, oxaloacetate, and amino group is catalyzed by amino acid kinase (FUB3).
Hydrolase encoded by FUB4 transform the product of this reaction to fusarate [171].
FUB1 gene (designed also as PKS21 according to the nomenclature proposed by
Hansen et al. [55]) plays a significant role in FA biosynthesis. Orthologs of this gene
were found in F. fujikuroi, F. verticillioides, F. oxysporum, F. circinatum, and F.
226
Ł. Stępień et al.
beauvericin is also produced by a thiol template mechanism [160, 161]. However,
the two depsipeptide synthetases differ in their substrate selectiveness. Beauvericin
synthetase preferably accepts N-methyl-L-phenylalanine and some other aliphatic
hydrophobic amino acids. The efficiency of incorporation into the cyclodepsipeptide
framework decreases with the length of the side chain: N-methyl-L-phenylalanine
was easily replaced by ortho-, meta-, and para-fluoro-substituted phenylalanine
derivatives, as well as by N-methyl-L-leucine, N-methyl-L-norleucine, and
N-methyl-L-isoleucine residues [149]. Consequently, significant sequence homologies to some of the Fusarium enzymes were found [150], establishing a common
genetic background to depsipeptide biosynthesis. Previously, some Fusarium
species like Fusarium poae have been reported to produce ENNs and BEA simultaneously [162, 163], which is justified by the fact that both mycotoxins share
a common metabolic pathway and the co-occurrence of ENNs and BEA in field
samples infected by Fusarium spp. has been observed [164, 165]. Previous works
demonstrate high probability that even a single PCR-based esyn1-specific marker
can detect potential producers of both toxins among Fusarium isolates originating
from contaminated plant material [130, 163].
5.1.5 Fusaric Acid
Fusaric acid (FA) is a picolinic acid derivative which was isolated for the first time
from Fusarium heterosporum strains. Further research have proven that other
Fusarium species, e.g., F. verticillioides, F. fujikuroi, and F. oxysporum, are also
able to produce this mycotoxin [166, 167]. FA shows moderate impact on mammalian health, but its high toxicity to plants is documented. It is responsible for
“fusarium wilt” development through the lipid peroxidation, increase of reactive
oxygen species, and, finally, host cells’ death [168]. FA also causes bakanae disease
in rice seedlings and has a strong antimicrobial activity, inhibiting quorum sensing in
Gram-negative bacteria [169, 170].
Biosynthetic pathway of fusaric acid remains largely unexplored; however, the
gene cluster responsible for encoding of proteins involved in this process has been
identified in F. verticillioides. Initially, only 5 genes were described in fusaric acid
biosynthetic (FUB) gene cluster, but just a few years later, additional 7 contiguous
genes were located 14.6 kb upstream of the previous five genes identified [171, 172].
These genes are conserved in genomes of all FA-producing Fusarium strains, and no
significant differences in cluster organization between the species have been found
[167]. Functions of all 12 FUB genes were predicted using BLAST analysis (Table 2)
[172, 173].
Fusaric acid synthase encoded by FUB1 is responsible for the synthesis of sixcarbon polyketide chain using three acetyl-CoA molecules. Fusion of polyketide
chain, oxaloacetate, and amino group is catalyzed by amino acid kinase (FUB3).
Hydrolase encoded by FUB4 transform the product of this reaction to fusarate [171].
FUB1 gene (designed also as PKS21 according to the nomenclature proposed by
Hansen et al. [55]) plays a significant role in FA biosynthesis. Orthologs of this gene
were found in F. fujikuroi, F. verticillioides, F. oxysporum, F. circinatum, and F.
226
Ł. Stępień et al.