have accumulated enough intraspecific polymorphisms to be explored as promising
targets for phylogenetic studies [3, 125].
5.1.4 Enniatins and Beauvericins
Enniatins (ENNs) and beauvericin (BEA) belong to a structurally and genetically
related group of nonribosomal cyclic hexadepsipeptides consisting of alternating
D-2-hydroxyisovaleric (d-HIV) acid and N-methyl-L-amino acids. The subunits are
linked by peptide bonds and intramolecular ester (lactone) bonds, forming a cyclic
depsipeptide [128, 129]. In the type A and B enniatins, these building blocks are
typically either aliphatic N-methyl-valine, N-methyl-isoleucine, or a mixture of these
amino acids [130]. In canonical beauvericin molecule, the three amino acid
substituents are all aromatic N-methyl-phenylalanines instead of aliphatic residues
[129, 131]. Also the identified three analogs of beauvericin (A, B, C) contain one,
two, or three groups of 2-hydroxyisocaproic acid (HMP) instead of HIV group,
respectively [132].
To date, 29 naturally occurring enniatin analogs have been identified. The most
frequent variants detected in foods and feeds, especially in cereals, are enniatin A, A 1
(ENN A 1 ), B (ENN B), B 1 (ENN B 1 ), and B 4 (ENN B 4 ), together with smaller
amounts of enniatins C, D, E, and F [128]. Enniatins are of high interest, because
of their wide range of biological activities. Structural differences related to the
N-methyl-L-amino acid are responsible for the different bioactivities of these mycotoxins. A mixture of ENNs can cause cytotoxic effects of various severities at low
concentrations and on different types of cells [133]. Affected cells frequently include
human cancer cells, implicating the potential use of ENNs as anticancer drugs [134].
In particular, ENNs A 1 and B 1 induce apoptotic cell death and disrupt the extracellular signal-regulated protein kinase’s (ERK) activity associated with cell proliferation. This bioactivity has long been assumed to be associated with their ionophoric
properties [135]. Today, the depsipeptides are known to incorporate into cell membranes and form pores with a high affinity for K
+
, Na
+ , Mg
2+ , and Ca
2+ [136]. ENNs
also exhibit different biological properties, such as insecticidal and antibiotic activity
against Mycobacterium sp. and Plasmodium falciparum. Of particular interest is the
proven action of identified ENNs as inhibitors of major drug efflux pumps in
Saccharomyces cerevisiae [137–140].
The chemical properties of depsipeptide compounds allow for their application in
pharmaceutical products with anti-inflammatory and antibiotic properties in targeted
treatment of diseases of the upper respiratory tract [141]. A mixture of enniatins was
shown by Gaumann et al. (1960) to act synergistically as complex phytotoxin in
causing wilt and necrosis to leaves of plants affected by Fusarium [142]. Pertinently,
enniatins are often found in cereal grain at high concentrations, as a result of fungal
infection. This fact has yet unknown implications for human and animal health,
which leads to depsipeptide perception as emerging mycotoxins [143, 144].
Beauvericin (BEA) is a cyclodepsipeptide ionophore transporting monovalent
cations across membranes as a free carrier uncoupling oxidative phosphorylation.
BEA displays a diverse array of biological activities in vitro [145] and is one of the
most potent cholesterol acyltransferase inhibitors of microbial origin. It shows
224
Ł. Stępień et al.
targets for phylogenetic studies [3, 125].
5.1.4 Enniatins and Beauvericins
Enniatins (ENNs) and beauvericin (BEA) belong to a structurally and genetically
related group of nonribosomal cyclic hexadepsipeptides consisting of alternating
D-2-hydroxyisovaleric (d-HIV) acid and N-methyl-L-amino acids. The subunits are
linked by peptide bonds and intramolecular ester (lactone) bonds, forming a cyclic
depsipeptide [128, 129]. In the type A and B enniatins, these building blocks are
typically either aliphatic N-methyl-valine, N-methyl-isoleucine, or a mixture of these
amino acids [130]. In canonical beauvericin molecule, the three amino acid
substituents are all aromatic N-methyl-phenylalanines instead of aliphatic residues
[129, 131]. Also the identified three analogs of beauvericin (A, B, C) contain one,
two, or three groups of 2-hydroxyisocaproic acid (HMP) instead of HIV group,
respectively [132].
To date, 29 naturally occurring enniatin analogs have been identified. The most
frequent variants detected in foods and feeds, especially in cereals, are enniatin A, A 1
(ENN A 1 ), B (ENN B), B 1 (ENN B 1 ), and B 4 (ENN B 4 ), together with smaller
amounts of enniatins C, D, E, and F [128]. Enniatins are of high interest, because
of their wide range of biological activities. Structural differences related to the
N-methyl-L-amino acid are responsible for the different bioactivities of these mycotoxins. A mixture of ENNs can cause cytotoxic effects of various severities at low
concentrations and on different types of cells [133]. Affected cells frequently include
human cancer cells, implicating the potential use of ENNs as anticancer drugs [134].
In particular, ENNs A 1 and B 1 induce apoptotic cell death and disrupt the extracellular signal-regulated protein kinase’s (ERK) activity associated with cell proliferation. This bioactivity has long been assumed to be associated with their ionophoric
properties [135]. Today, the depsipeptides are known to incorporate into cell membranes and form pores with a high affinity for K
+
, Na
+ , Mg
2+ , and Ca
2+ [136]. ENNs
also exhibit different biological properties, such as insecticidal and antibiotic activity
against Mycobacterium sp. and Plasmodium falciparum. Of particular interest is the
proven action of identified ENNs as inhibitors of major drug efflux pumps in
Saccharomyces cerevisiae [137–140].
The chemical properties of depsipeptide compounds allow for their application in
pharmaceutical products with anti-inflammatory and antibiotic properties in targeted
treatment of diseases of the upper respiratory tract [141]. A mixture of enniatins was
shown by Gaumann et al. (1960) to act synergistically as complex phytotoxin in
causing wilt and necrosis to leaves of plants affected by Fusarium [142]. Pertinently,
enniatins are often found in cereal grain at high concentrations, as a result of fungal
infection. This fact has yet unknown implications for human and animal health,
which leads to depsipeptide perception as emerging mycotoxins [143, 144].
Beauvericin (BEA) is a cyclodepsipeptide ionophore transporting monovalent
cations across membranes as a free carrier uncoupling oxidative phosphorylation.
BEA displays a diverse array of biological activities in vitro [145] and is one of the
most potent cholesterol acyltransferase inhibitors of microbial origin. It shows
224
Ł. Stępień et al.