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Detoxification of Mycotoxins through Biotransformation

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Mycotoxins are toxic fungal secondary metabolites that pose a major threat to the safety of food and feed. Mycotoxins are usually converted into less toxic or non-toxic metabolites through biotransformation that are often made by living organisms as well as the isolated enzymes. The conversions mainly include hydroxylation, oxidation, hydrogenation, de-epoxidation, methylation, glycosylation and glucuronidation, esterification, hydrolysis, sulfation, demethylation and deamination. Biotransformations of some notorious mycotoxins such as alfatoxins, alternariol, citrinin, fomannoxin, ochratoxins, patulin, trichothecenes and zearalenone analogues are reviewed in detail. The recent development and applications of mycotoxins detoxification through biotransformation are also discussed.
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toxins
Review
Detoxification of Mycotoxins
through Biotransformation
Peng Li 1, Ruixue Su 1, Ruya Yin 1, Daowan Lai 1, Mingan Wang 2, Yang Liu 3
and Ligang Zhou 1, *
1Department of Plant Pathology, College of Plant Protection, China Agricultural University,
Beijing 100193, China; peng_li0429@163.com (P.L.); ruixuesu07@163.com (R.S.); ruyayin1206@163.com (R.Y.);
dwlai@cau.edu.cn (D.L.)
2
Department of Applied Chemistry, College of Sciences, China Agricultural University, Beijing 100193, China;
wangma@cau.ed.cn
3
Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China;
liuyang01@caas.cn
*Correspondence: lgzhou@cau.edu.cn; Tel.: +86-10-6273-1199
Received: 30 December 2019; Accepted: 12 February 2020; Published: 14 February 2020

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Abstract:
Mycotoxins are toxic fungal secondary metabolites that pose a major threat to the safety
of food and feed. Mycotoxins are usually converted into less toxic or non-toxic metabolites
through biotransformation that are often made by living organisms as well as the isolated
enzymes. The conversions mainly include hydroxylation, oxidation, hydrogenation, de-epoxidation,
methylation, glycosylation and glucuronidation, esterification, hydrolysis, sulfation, demethylation
and deamination. Biotransformations of some notorious mycotoxins such as alfatoxins, alternariol,
citrinin, fomannoxin, ochratoxins, patulin, trichothecenes and zearalenone analogues are reviewed
in detail. The recent development and applications of mycotoxins detoxification through
biotransformation are also discussed.
Keywords:
fungi; mycotoxins; phytotoxins; detoxification; biotransformation; living organisms;
enzymes; food safety and feed safety
Key Contribution:
This review provides insight into detoxification of mycotoxins through
biotransformation which should be a strategy for the management of mycotoxins in foods and feeds.
1. Introduction
Mycotoxins are toxic secondary metabolites produced by fungi mainly belonging to the genera
of Alternaria,Aspergillus,Fusarium and Penicillium. Mycotoxins may infer serious risks such as
carcinogenic, teratogenic, mutagenic and immunosuppressive eects on animal and human health,
and lead to economic loses. Several detoxification strategies, including physical [
1
,
2
], chemical [
3
]
and biotransformation [
4
8
] approaches, have been reported. Chemical strageties use acids, bases,
oxidizing agents and aldehydes to modify the structure of mycotoxins, which has led to increased
public concerns over the chemical residues in food and feed [
9
,
10
]. Some physical strategies such as
the application of adsorption agents presented no sucient eect against mycotoxins [11]. Although
physical and chemical methods for mycotoxin detoxification met with varying degrees of success,
limited ecacy and losses of important nutrients still hamper their applications in food industries [
11
].
In contrast, biotransformation methods, which have high specificity, produce harmless products, and
even lead to complete detoxification under mild and environmentally friendly conditions, have been
recognized as the promising solution for decontamination of mycotoxins [
6
,
11
]. Living organisms
Toxins 2020,12, 121; doi:10.3390/toxins12020121 www.mdpi.com/journal/toxins
Toxins 2020,12, 121 2 of 37
including bacteria, fungi, plants and animals, as well as the isolated enzymes, have been used for
biotransformation. They are able to metabolize, destroy or deactivate mycotoxins into stable, less toxic
or even nontoxic products [12].
To our knowledge, no detailed review has focused on detoxification of mycotoxins through
biotransformation though a series of reviews on the detoxification of certain mycotoxins have been
published over the last 20 years [
4
,
5
,
7
,
8
,
13
19
]. Furthermore, significant advances in the knowledge
on detoxification of mycotoxins by biotransformation have been achieved recently. This mini-review
mainly presents detoxification of mycotoxins through biotransformation of bacteria, fungi, plants
and animals, as well as the isolated enzymes, with specific attentions to the reaction types, and
detoxifications of some important mycotoxins.
2. Reaction Types of Mycotoxin Biotransformation
The reaction types involved in the mycotoxin biotransformations are summarized according
to the classes of chemical reactions as follows: (i) hydroxylation; (ii) oxido-reduction between
alcohols and ketones; (iii) hydrogenation of the carbon-carbon double bond; (iv) de-epoxidation; (v)
methylation; (vi) glycosylation and glucuronidation; (vii) esterification; (viii) hydrolysis; (ix) sulfation;
(x) demethylation; (xi) deamination; and (xii) miscellaneous reactions. The substrates, products,
bioconversion systems including organisms or enzymes participating in the biotransformations of
mycotoxins are summarized in Tables 113. The corresponding conversion reactions are shown in
Figures S1–S76 (see Supplementary Materials).
2.1. Hydroxylation
Hydroxylation of mycotoxins is a biotransformation process that introduces a hydroxyl group
(-OH) into the molecule (Table 1). Regio- and stereoselective introduction of hydroxyl groups
at the various positions of the molecule are often facilitated by the enzymes called hydroxylases.
Hydroxylation often increases the polarity of mycotoxins, and reduce their toxicity.
Aflatoxin B
1
(AFB
1
,
1
) was converted to either aflatoxin M
1
(AFM
1
,
2
) (Figure S1) by channel
catfish liver [
20
] or aflatoxin Q
1
(AFQ
1
,
3
) by rat liver microsomal cytochrome P450p [
21
]. AFB
1
(
1
) was
also simultaneously hydroxylated to AFM
1
(
2
) and AFQ
1
(
3
) by hepatic microsomal mixed-function
oxidase from the rhesus monkey [
22
]. Similarly, aflatoxin B
2
(AFB
2
,
4
) was simultaneously converted
to aflatoxin M2(AFM2,5) and aflatoxin Q2(AFQ2,6) by animal liver microsomes (Figure S2) [14].
Both alternariol (AOH,
7
) and alternariol 9-O-methyl ether (AME,
8
) are the main mycotoxins
produced by the fungi from the genus Alternaria. The monohydroxylated products of AOH (
7
) and
AME (
8
) were identified as 2-hydroxy AOH (
9
), 4-hydroxy AOH (
10
), 8-hydroxy AOH (
11
) and
10-hydroxy AOH (
12
), 2-hydroxy AME (
13
), 4-hydroxy AME (
14
), 8-hydroxy AME (
15
) and 10-hydroxy
AME (
16
), when AOH (
7
) and AME (
8
) were, respectively, incubated with the microsomes from rat,
human and porcine livers (Figures S3 and S4) [23].
Destruxin B (
17
) is a phytotoxin produced by the phytopathogenic fungus Alternaria brassicae.
Destruxin B (
17
) can be detoxified into hydroxydestruxin B (
18
) by the hydroxylase from cruciferous
plants such as Brassica napus (Figure S5). It was considered as an important detoxification step made
by the host plant [24,25].
Fusaric acid (FA,
19
), also called 5-butylpicolinic acid, is a host non-specific phytotoxin produced
by the fungi from the genus Fusarium [
26
]. FA (
19
) was converted to 8-hydroxyfusaric acid (
20
) with
hydroxylation by the fungus Mucor rouxii (Figure S6) [27].
Ochratoxin A (OTA,
21
) consists of a chlorinated dihydroisocoumarin linked through a
7-carboxyl group to L-phenylalanine by an amide bond. OTA (
21
) was hydroxylated into
7-carboxy-(2
0
-hydroxy-1-phenylalanine-amide)-5-chloro-8-hydroxy-3,4-dihydro-3R- methylisocoumarin
(
22
) and a dihydrodiol derivative (
23
) by a Gram-negative bacterium Phenylobacterium immobile
(Figure S7) [28].
Toxins 2020,12, 121 3 of 37
(4R)-4-Hydroxyochratoxin A (
24
), or 4-hydroxyochratoxin A, was isolated from the urine of rats
after injection with OTA (
21
), which indicated that OTA (
21
) was converted to (4R)-4-hydroxyochratoxin
A (24) (Figure S8) [29].
OTA (
21
) was hydroxylated into (4R)-4-hydroxyochratoxin A (
24
) and (4S)-4-hydroxyochratoxin
A (25) as well as 10-hydroxyochratoxin A (26) by rabbit liver microsomes (Figure S9) [30,31].
When ochratoxin B (OTB,
27
) was incubated with horse radish peroxidase (HPR), the high level
of the hydroquinone metabolite of ochratoxin (OTHQ,
28
) was produced (Figure S10). It indicated that
the hydroquinone redox couple played a significant role in OTB-mediated toxicity [32].
Sterigmatocystin (STC,
29
) was found to be produced by more than 30 fungal species, particularly
by Aspergillus species such as A. flavus,A. parasiticus,A. versicolor and A. nidulans [
33
]. STC (
29
) has an
aflatoxin-like structure including a furofuran ring system. Like AFB
1
(
1
), STC (
29
) is a liver carcinogen
and forms DNA adducts after metabolic activation to an eposide at the furofuran ring. Incubation of
STC (
29
) with the hepatic microsomes of humans and rats, 9-hydroxy-STC (
30
) via hydroxylation of
STC (29) aromatic ring was formed (Figure S11) [34].
T-2 toxin (
31
) was principally produced by dierent Fusarium species, detected in many
crops including oats, wheat and barley. Enzyme CYP3A37 hydrolyzed the conversion of T-2
toxin (
31
) to 19-OH T-2 toxin (or called 3
0
-OH T-2 toxin,
32
) by chicken CYP3A37 reconstituted
with NAPH-cytochrome P450 reductase (CPR) and cytochrome b5 produced by Escherichia coli
(Figure S12) [
35
]. In addition, the heterologously expressed CYP1A5 in HeLa cells also metabolized
T-2 toxin (
31
) into 19-OH T-2 toxin (
32
) by the 19-hydroxylation of isovaleryl group [
36
]. 19-Hydroxy
T-2 toxin (
32
) has been found to be more toxic than T-2 toxin (
31
). Therefore, it will be more toxic to the
body when T-2 toxin (31) is transformed to 19-OH T-2 toxin (32) in humans and animals [37].
Zearalenone (ZEN,
33
) was converted into (5S)-5-hydroxy ZEN (
34
) with hydroxylation of the
aliphatic ring of ZEN (
33
) by the fungus Cunninghamella bainieri (Figure S13) [
38
]. By using reference
compounds and ZEN (
33
) labeled with deuterium at specific positions, evidence was provided for
the preferential hydroxylation of ZEN (
33
) at C-8 and, to a lesser extent, at C-5, C-9 and C-10 with rat
liver microsomes. The stereochemistry of the aliphatic hydroxylation products of ZEN (
33
) needs to be
further studied [
39
]. In addition, ZEN (
33
) was converted into two monohydroxylated metabolites
namely 13-hydroxy-ZEN (
35
) and 15-hydroxy-ZEN (
36
) with aromatic hydroxylation by human hepatic
(liver) microsomes (Figure S14) [40].
Table 1. Hydroxylation of mycotoxins.
Substrate Product Biotransformation System Ref.
Aflatoxin B1(AFB1,1) Aflatoxins M1(2) and Q1(3)Hepatic microsomal mixed-function
oxidase of rhesus monkey [22]
Aflatoxin M1(2) Channel catfish liver [20]
Aflatoxin Q1(3)Rat liver microsomal cytochrome
P450p [21]
Aflatoxin B2(AFB2,4) Aflatoxins M2(5) and Q2(6) Animal liver microsomes [14]
Alternariol (AOH, 7) 2-Hydroxy AOH (9)Microsomes from rat, human and
porcine liver [23]
4-Hydroxy AOH (10)Microsomes from rat, human and
porcine liver [23]
8-Hydroxy AOH (11)Microsomes from rat, human and
porcine liver [23]
10-Hydroxy AOH (12)Microsomes from rat, human and
porcine liver [23]
Alternariol 9-O-methyl
ether (AME, 8)2-Hydroxy AME (13)Microsomes from rat, human and
porcine liver [23]
4-Hydroxy AME (14)Microsomes from rat, human and
porcine liver [23]
8-Hydroxy AME (15)Microsomes from rat, human and
porcine liver [23]
Toxins 2020,12, 121 4 of 37
Table 1. Cont.
Substrate Product Biotransformation System Ref.
10-Hydroxy AME (16)Microsomes from rat, human and
porcine liver [23]
Destruxin B (17) Hydroxydestruxin B (18) Crucifers such as Brassica napus [24]
Fusaric acid (19) 8-Hydroxyfusaric acid (20)Mucor rouxii (fungus) [27]
Ochratoxin A(OTA, 21)
7-Carboxy-(20-hydroxy-1-
phenylalanine-amide)-
5-chloro-8-hydroxy-3,4-dihydro-3R-
methylisocoumarin (22)
Phenylobacterium immobile (bacterium) [28]
Dihydrodiol derivative of ochratoxin A
(23)Phenylobacterium immobile (bacterium) [28]
(4R)-4-Hydroxyochratoxin A (24) Rat liver microsomes [29]
Cell cultures of wheat and maize [29]
Rabbit liver microsomes [30]
(4S)-4-Hydroxyochratoxin A (25) Cell cultures of wheat and maize [31]
Rabbit liver microsomes [30]
10-Hydroxyochratoxin A (26) Rabbit liver microsomes [30]
Ochratoxin B (OTB, 27)Hydroquinone metabolite of ochratoxin
(OTHQ, 28)Horse radish peroxidase (HPR) [32]
Sterigmatocystin (29) 9-Hydroxy sterigmatocystin (30) Human and rat hepatic microsomes [34]
T-2 toxin (31) 19-OH T-2 toxin =3‘-OH T-2 toxin (32) Chicken CYP3A37 (enzyme) [35]
Zearalenone (ZEN, 33) (5S)-5-Hydroxy ZEN (34)Cunninghamella bainieri (fungus) [38]
13-Hydroxy ZEN (35) Human liver microsomes [40]
15-Hydroxy ZEN (36) Human liver microsomes [40]
Toxins 2020, 12, x FOR PEER REVIEW 4 of 37
hydroxy-3,4-dihydro-3R-
methylisocoumarin (22)
Dihydrodiol derivative of ochratoxin A
(23) Phenylobacterium immobile (bacterium) [28]
(4R)-4-Hydroxyochratoxin
A
(24) Rat liver microsomes [29]
Cell cultures of wheat and maize [29]
Rabbit liver microsomes [30]
(4S)-4-Hydroxyochratoxin
A
(25) Cell cultures of wheat and maize [31]
Rabbit liver microsomes [30]
10-Hydroxyochratoxin
A
(26) Rabbit liver microsomes [30]
Ochratoxin B (OTB,
27)
Hydroquinone metabolite of ochratoxin
(OTHQ, 28) Horse radish peroxidase (HPR) [32]
Sterigmatocystin
(29) 9-Hydroxy sterigmatocystin (30) Human and rat hepatic microsomes [34]
T-2 toxin (31) 19-OH T-2 toxin = 3‘-OH T-2 toxin (32) Chicken CYP3A37 (enzyme) [35]
Zearalenone (ZEN,
33) (5S)-5-Hydroxy ZEN (34) Cunninghamella bainieri (fungus) [38]
13-Hydroxy ZEN (35) Human liver microsomes [40]
15-Hydroxy ZEN (36) Human liver microsomes [40]
Toxins 2020,12, 121 5 of 37
Toxins 2020, 12, x FOR PEER REVIEW 5 of 37
2.2. Oxido-Reduction between Alcohols and Ketones
Oxido-reduction between alcohols and ketones of mycotoxins include: (i) oxidation of the
hydroxyl group and (ii) reduction of the carbonyl group (Table 2).
Aflatoxin B1 (AFB1, 1) was converted into alflatoxicol (37) through reduction of the keto group
to the hydroxyl group by several fungi such as Eurotium herbariorum, Rhizopus sp. and non-aflatoxin-
producing Aspergillus flavus (Figure S15) [41].
A dehydrogenase responsible for the selective oxidation of deoxynivalenol (DON, 38) at C-3
position by converting DON (38) to 3-keto-DON (39) was revealed from the bacterium Devosia sp.
(Figure S16) [42].
Fomannoxin (40) is a benzohydrofuran phytotoxin that was produced by the forest pathogen
Heterobasidion annosum during the infection process [43]. When fomannoxin (40) was added in the cell
cultures of Pinus sylvestris, the phytotoxin was transformed into the non-toxic formannoxin alcohol
(41) (Figure S17) [44].
Zearalonone (ZEN, 33) was transformed to both α-zearalenol (α-ZEL, 42) and β-zearalenol (β-
ZEL, 43) with reduction by the fungi Candida tropicalis (Figure S18) [45], Saccharomyces cerevisae [46],
Torulaspora delbruckii [46] and Zygosaccharomyces rouxii [46]. In contrast, only α-ZEL (42) was
transformed from ZEA by Pichia fermentans and several yeast strains of the genera Candida, Hansenula,
Brettanomyces, Schizosaccharornyces and Saccharomycopsis [46], as well as Rhizopus sp. and Aspergillus
sp. [47].
Table 2. Oxido-reduction between alcohols and ketones of mycotoxins.
Substrate Product Biotransformation System Ref.
Aflatoxin B1
(AFB1, 1) Aflatoxicol (37) Fungi Aspergillus niger, Eurotium herbariorum, Rhizopus sp. [41]
Deoxynivalenol
(DON, 38)
3-Keto-DON
(39) Devosia mutans (bacterium) [42]
Fomannoxin (40) Fomannoxin
alcohol (41) Pinus sylvestris cell cultures [44]
Rhizosphere-associated bacterium Streptomyces sp. AcH 505 [48]
Zearalenone
(ZEN, 33)
α-Zearalenol
(42) Candida tropicalis (fungus) [45]
Fungi: Saccharomyces cerevisae, Torulaspora delbruckii, Zygosaccharomyces
rouxii, Pichia fermentans, and several yeast strains of the genera Candida,
Hansenula, Brettanomyces, Schizosaccharornyces and Saccharomycopsis
[46]
2.2. Oxido-Reduction between Alcohols and Ketones
Oxido-reduction between alcohols and ketones of mycotoxins include: (i) oxidation of the hydroxyl
group and (ii) reduction of the carbonyl group (Table 2).
Aflatoxin B
1
(AFB
1
,
1
) was converted into alflatoxicol (
37
) through reduction of the keto group to the
hydroxyl group by several fungi such as Eurotium herbariorum,Rhizopus sp. and non-aflatoxin-producing
Aspergillus flavus (Figure S15) [41].
A dehydrogenase responsible for the selective oxidation of deoxynivalenol (DON,
38
) at C-3
position by converting DON (
38
) to 3-keto-DON (
39
) was revealed from the bacterium Devosia sp.
(Figure S16) [42].
Fomannoxin (
40
) is a benzohydrofuran phytotoxin that was produced by the forest pathogen
Heterobasidion annosum during the infection process [
43
]. When fomannoxin (
40
) was added in the cell
cultures of Pinus sylvestris, the phytotoxin was transformed into the non-toxic formannoxin alcohol
(41) (Figure S17) [44].
Zearalonone (ZEN,
33
) was transformed to both
α
-zearalenol (
α
-ZEL,
42
) and
β
-zearalenol (
β
-ZEL,
43
) with reduction by the fungi Candida tropicalis (Figure S18) [
45
], Saccharomyces cerevisae [
46
], Torulaspora
delbruckii [
46
] and Zygosaccharomyces rouxii [
46
]. In contrast, only
α
-ZEL (
42
) was transformed from
ZEA by Pichia fermentans and several yeast strains of the genera Candida,Hansenula,Brettanomyces,
Schizosaccharornyces and Saccharomycopsis [46], as well as Rhizopus sp. and Aspergillus sp. [47].
Table 2. Oxido-reduction between alcohols and ketones of mycotoxins.
Substrate Product Biotransformation System Ref.
Aflatoxin B1(AFB1,1) Aflatoxicol (37)Fungi Aspergillus niger,Eurotium herbariorum,
Rhizopus sp. [41]
Deoxynivalenol (DON, 38) 3-Keto-DON (39)Devosia mutans (bacterium) [42]
Fomannoxin (40) Fomannoxin alcohol (41)Pinus sylvestris cell cultures [44]
Rhizosphere-associated bacterium Streptomyces
sp. AcH 505 [48]
Zearalenone(ZEN, 33)α-Zearalenol (42)Candida tropicalis (fungus) [45]
Fungi: Saccharomyces cerevisae,Torulaspora
delbruckii,Zygosaccharomyces rouxii,Pichia
fermentans, and several yeast strains of the genera
Candida,Hansenula,Brettanomyces,
Schizosaccharornyces and Saccharomycopsis
[46]
Fungi Rhizopus sp. and Aspergillus sp. [47]
Toxins 2020,12, 121 6 of 37
Table 2. Cont.
Substrate Product Biotransformation System Ref.
β-Zearalenol (43)Candida tropicalis (fungus) [45]
Fungi: Saccharomyces cerevisae,Torulaspora
delbruckii and Zygosaccharomyces rouxii [46]
Toxins 2020, 12, x FOR PEER REVIEW 6 of 37
Fungi Rhizopus sp. and Aspergillus sp. [47]
β-Zearalenol
(43) Candida tropicalis (fungus) [45]
Fungi: Saccharomyces cerevisae, Torulaspora delbruckii and
Zygosaccharomyces rouxii [46]
2.3. Hydrogenation of the Carbon-Carbon Double Bond
Hydrogenation of the carbon-carbon double bond of mycotoxins means the reduction of a C-C
double bond through biotransformation (Table 3). Aflatoxin B1 (AFB1, 1) was converted to AFB2 (4)
with hydrogenation by the fungus Penicillium raistrickii (Figure S19) [14]. Zearalenone (ZEN, 33) was
transformed to zearalanone (ZAN, 44) with reduction of the carbon-carbon bond in ovine (Figure S20)
[49].
Table 3. Reduction of the carbon-carbon double bond of mycotoxins.
Substrate Product Biotransformation System Ref.
Aflatxin B1 (AFB1, 1) Aflatoxin B2 (AFB2, 4) Penicillium raistrickii (fungus) [14]
Zearalenone (ZEN, 33) Zearalanone (ZAN, 44) Ovine [49]
2.4. De-Epoxidation
De-epoxidation of mycotoxins is commonly found in trichothecene analogues (Table 4) [50,51].
Trichothecene toxicity depends heavily upon the epoxide moiety of the molecule, and opening the
epoxide ring dramatically reduces the toxicity [52].
Deoxynivalenol (DON, 38) was converted to deepoxydeoxynivalenol (DOM, 45) with de-
epoxidation by Eubacterium sp. DSM11798 (Figure S21) [50].
Nivalenol (NIV, 46) belongs to group B trichothecenes. NIV (46) was converted to de-
epoxynivalenol (de-epoxy-NIV, 47) with de-epoxidation by the bacterium Eubacterium sp. BBSH 797
Table 3. Reduction of the carbon-carbon double bond of mycotoxins.
Substrate Product Biotransformation System Ref.
Aflatxin B1(AFB1,1) Aflatoxin B2(AFB2,4)Penicillium raistrickii (fungus) [14]
Zearalenone (ZEN, 33) Zearalanone (ZAN, 44) Ovine [49]
2.3. Hydrogenation of the Carbon-Carbon Double Bond
Hydrogenation of the carbon-carbon double bond of mycotoxins means the reduction of a C-C
double bond through biotransformation (Table 3). Aflatoxin B
1
(AFB
1
,
1
) was converted to AFB
2
(
4
)
with hydrogenation by the fungus Penicillium raistrickii (Figure S19) [
14
]. Zearalenone (ZEN,
33
) was
transformed to zearalanone (ZAN,
44
) with reduction of the carbon-carbon bond in ovine (Figure
S20) [49].
2.4. De-Epoxidation
De-epoxidation of mycotoxins is commonly found in trichothecene analogues (Table 4) [
50
,
51
].
Trichothecene toxicity depends heavily upon the epoxide moiety of the molecule, and opening the
epoxide ring dramatically reduces the toxicity [52].
Deoxynivalenol (DON,
38
) was converted to deepoxydeoxynivalenol (DOM,
45
) with
de-epoxidation by Eubacterium sp. DSM11798 (Figure S21) [50].
Nivalenol (NIV,
46
) belongs to group B trichothecenes. NIV (
46
) was converted to
de-epoxynivalenol (de-epoxy-NIV,
47
) with de-epoxidation by the bacterium Eubacterium sp. BBSH
Toxins 2020,12, 121 7 of 37
797 (Figure S22) [
51
]. Similarly, after the male Wistar rats were orally administered with NIV
(
46
), a metabolite was isolated from rat feces and identified as de-epoxy-NIV (
47
), namely
3,4,7,15-tetrahydroxytrichothec-8,12-dien-8-one (Figure S22) [53].
Table 4. De-epoxidation of mycotoxins.
Substrate Product Biotransformation System Ref.
Deoxynivalenol (DON, 38) Deepoxydeoxynivalenol
(DOM, 45)
Eubacterium sp. DSM 11,798
(bacterium)
[50]
Nivalenol (NIV, 46) De-epoxy NIV (47)Euacterium sp. BBSH 797
(bacterium)
[51]
Wistar rats [53]
Toxins 2020, 12, x FOR PEER REVIEW 7 of 37
(Figure S22) [51]. Similarly, after the male Wistar rats were orally administered with NIV (46), a
metabolite was isolated from rat feces and identified as de-epoxy-NIV (47), namely 3,4,7,15-
tetrahydroxytrichothec-8,12-dien-8-one (Figure S22) [53].
Table 4. De-epoxidation of mycotoxins.
Substrate Product Biotransformation System Ref.
Deoxynivalenol (DON,
38)
Deepoxydeoxynivalenol (DOM,
45)
Eubacterium sp. DSM 11,798
(bacterium)
[50]
Nivalenol (NIV, 46) De-epoxy NIV (47) Euacterium sp. BBSH 797 (bacterium) [51]
Wistar rats [53]
2.5. Other Oxido-Reductions
Other oxido-reductions of mycotoxins include epoxidation, oxidation of alcohols to acids,
reduction of acids to alcohols, and multi-step oxido-reductions (Table 5). Aflatoxin B1 (AFB1, 1) was
catalyzed into AFB1-8,9-epoxide (48) by channel catfish liver microsomes (Figure S23) [20]. AFB1 (1)
was also transformed to AFB1-8,9-dihydrodiol (49) by the fungus Phanerochaete sordia (Figure S24) [54].
Two Alternaria toxins with a perylene quinone structure, altertoxin II (ATX II, 50) and
stemphyltoxin III (STTX III, 51) were reduced to alcohols in human colon Caco-2 cells, resulting in
the formation of altertoxin I (ATX I, 52) and alteichin (ALTCH, 53), respectively (Figure S25). ATX II
(50) was also reduced to ATX I (52) in other human tumor cell lines such as HCT 116, HepG2 and V79
[55].
Botrydial (54) was converted to dihydrobotrydial (55) and secobotrytrienediol (56) with a few
oxido-reductions by the fungus Botrytis cinerea (Figure S26) [56].
Citrinin (CTN/CIT, 57) is a polyketide nephrotoxic mycotoxin commonly present as a natural
hazardous contaminant both in food and feed world wide. It was first isolated from the fungus
Penicillium citrinum [8]. Dihydrocitrinone (DH-CTN, 58) was detected as the main metabolite of CTN
(57) (Figure S27) in the urine of rats [57] and humans [58]. CTN (57) induced a concentration-
dependent increase in micronucleus frequencies at concentrations 30 μM, wheas DH-CTN (58)
showed no genotoxic effect up to 300 μM. Thus, conversion of CTN (57) to DH-CTN (58) in humans
can be regarded as a detoxification step [58].
Fomannoxin (40) is a phytotoxic dihydrobenzofuran produced by the fungi from genus
Heterobasidion (Fomes) [43]. Fomannoxin (40) was added to the cultures of rhizosphere-associated
Streptomyces sp. AcH 505, it was converted into different products by oxido-reduction, most of
products retained phytotoxic activity. These products included fomannoxin alcohol (41), fomannoxin
acid (59), fomannoxin amide (60), 2,3-dihydro-2-(2-hydroxyisopropanyl)-5-benzofurancarboxylic
acid (MFA-1, 61), 2,3-dihydro-3-hydroxyl-2-isopropenyl-5-benzofurancarboxylic acid or 3-hydroxyl-
fomannoxin acid (MFA-2, 62) and 2,3-dihydro-2-(1,2-dihydroxyisopropanyl)-5-
benzofurancarboxylic acid (DFA, 63) (Figure S28) [48].
Fusaric acid (FA, 19) was reduced to fusarinol (64), also called 5-butyl-2-pyridinemethanol, by
the fungus Aspergillus tubingensis (Figure S29) [59]. Fusarinol (64) was significantly less phytotoxic
than fusaric acid (19). In fusarinol (64), the acid has been reduced to an alcohol group. The reduced
phytotoxicity of fusarinol (64) indicates the importance of the carboxylic acid in the toxic function of
2.5. Other Oxido-Reductions
Other oxido-reductions of mycotoxins include epoxidation, oxidation of alcohols to acids, reduction
of acids to alcohols, and multi-step oxido-reductions (Table 5). Aflatoxin B
1
(AFB
1
,
1
) was catalyzed
into AFB
1
-8,9-epoxide (
48
) by channel catfish liver microsomes (Figure S23) [
20
]. AFB
1
(
1
) was also
transformed to AFB1-8,9-dihydrodiol (49) by the fungus Phanerochaete sordia (Figure S24) [54].
Two Alternaria toxins with a perylene quinone structure, altertoxin II (ATX II,
50
) and stemphyltoxin
III (STTX III,
51
) were reduced to alcohols in human colon Caco-2 cells, resulting in the formation
of altertoxin I (ATX I,
52
) and alteichin (ALTCH,
53
), respectively (Figure S25). ATX II (
50
) was also
reduced to ATX I (52) in other human tumor cell lines such as HCT 116, HepG2 and V79 [55].
Botrydial (
54
) was converted to dihydrobotrydial (
55
) and secobotrytrienediol (
56
) with a few
oxido-reductions by the fungus Botrytis cinerea (Figure S26) [56].
Citrinin (CTN/CIT,
57
) is a polyketide nephrotoxic mycotoxin commonly present as a natural
hazardous contaminant both in food and feed world wide. It was first isolated from the fungus
Penicillium citrinum [
8
]. Dihydrocitrinone (DH-CTN,
58
) was detected as the main metabolite of CTN
(
57
) (Figure S27) in the urine of rats [
57
] and humans [
58
]. CTN (
57
) induced a concentration-dependent
increase in micronucleus frequencies at concentrations
30
µ
M, wheas DH-CTN (
58
) showed no
genotoxic eect up to 300
µ
M. Thus, conversion of CTN (
57
) to DH-CTN (
58
) in humans can be
regarded as a detoxification step [58].
Fomannoxin (
40
) is a phytotoxic dihydrobenzofuran produced by the fungi from genus
Heterobasidion (Fomes) [
43
]. Fomannoxin (
40
) was added to the cultures of rhizosphere-associated
Streptomyces sp. AcH 505, it was converted into dierent products by oxido-reduction, most of products
retained phytotoxic activity. These products included fomannoxin alcohol (
41
), fomannoxin acid (
59
),
fomannoxin amide (
60
), 2,3-dihydro-2-(2
0
-hydroxyisopropanyl)-5-benzofurancarboxylic acid (MFA-1,
61
), 2,3-dihydro-3-hydroxyl-2-isopropenyl-5-benzofurancarboxylic acid or 3-hydroxyl-fomannoxin
acid (MFA-2,
62
) and 2,3-dihydro-2-(1
0
,2
0
-dihydroxyisopropanyl)-5-benzofurancarboxylic acid (DFA,
63) (Figure S28) [48].
Fusaric acid (FA,
19
) was reduced to fusarinol (
64
), also called 5-butyl-2-pyridinemethanol, by the
fungus Aspergillus tubingensis (Figure S29) [
59
]. Fusarinol (
64
) was significantly less phytotoxic than
fusaric acid (
19
). In fusarinol (
64
), the acid has been reduced to an alcohol group. The reduced
Toxins 2020,12, 121 8 of 37
phytotoxicity of fusarinol (
64
) indicates the importance of the carboxylic acid in the toxic function of
FA (
19
). The fungus A. tubingensis provides a novel detoxification mechanism against FA (
19
), which
may be utilized to control Fusarium wilt [59].
The marine yeast Kodameae ohmeri was found to transform patulin (PAT,
65
) into E-ascladiol (
66
)
and Z-ascladiol (
67
) through reduction (Figure S30). High transformation rate was at a temperature
of 35
C and pH between 3 and 6 that indicated the potential application of K. ohmeri for PAT (
65
)
detoxification of the contaminated products [
60
]. E-ascladiol (
66
) and Z-ascladiol (
67
) have been
found to exhibit no signs of toxicity towards human cell lines derived from the intestinal tract, kidney,
liver and immune system, which demonstrates that PAT (
65
) detoxification strategies leading to the
accumulation of ascladiols should be approaches to limit the PAT (
65
) risk [
61
]. When PAT (
65
) was
added in the cell cultures or cell-free supernatant of Lactobacillus plantarum, it was transformed to
E-ascladiol (
66
) and Z-ascladiol (
67
), which were further transformed into hydroascladiol (
68
) over a
4-week cell-free incubation at 4 C (Figure S31) [62].
Table 5. Other oxido-reductions of mycotoxins.
Substrate Product Biotransformation System Ref.
Aflatoxin B1(AFB1,1) AFB1-8,9-epoxide (48) Channel catfish liver [20]
AFB1-8,9-dihydrodiol (49)Phanerochaete sordida YK-624
(fungus)
[54]
Altertoxin II (50) Altertoxin I (52)
Mammalian cell lines Caco-2, HCT
116, HepG2, V79
[55]
Stemphyltoxin III (51) Alteichin (53) Mammalian cell line Caco-2 [55]
Botrydial (54) Dihydrobotrydial (55)Botrytis cinerea (fungus) [56]
Secobotrytrienediol (56)Botrytis cinerea (fungus) [56]
Citrinin (57) Dihydrocitrinone (58) Rats and humans [57]
Fomannoxin (40) Fomannoxin acid (59)
Rhizosphere-associated bacterium
Streptomyces sp. AcH 505
[48]
Fomannoxin amide (60)
Rhizosphere-associated bacterium
Streptomyces sp. AcH 505
[48]
MFA-1 (61)
Rhizosphere-associated bacterium
Streptomyces sp. AcH 505
[48]
MFA-2 (62)
Rhizosphere-associated bacterium
Streptomyces sp. AcH 505
[48]
DFA (63)
Rhizosphere-associated bacterium
Streptomyces sp. AcH 505
[48]
Fusaric acid (19) Fusarinol (64)Aspergillus tubingensis (fungus) [59]
Patulin (65)E-Ascladiol (66),
Z-ascladiol (67)
Kodameae ohmeri (fungus) [60]
E-Ascladiol (66),
Z-ascladiol (67),
hydroascladiol (68)
Lactobacillus plantarum (bacterium)
[62]
Toxins 2020, 12, x FOR PEER REVIEW 8 of 37
FA (19). The fungus A. tubingensis provides a novel detoxification mechanism against FA (19), which
may be utilized to control Fusarium wilt [59].
The marine yeast Kodameae ohmeri was found to transform patulin (PAT, 65) into E-ascladiol (66)
and Z-ascladiol (67) through reduction (Figure S30). High transformation rate was at a temperature
of 35 °C and pH between 3 and 6 that indicated the potential application of K. ohmeri for PAT (65)
detoxification of the contaminated products [60]. E-ascladiol (66) and Z-ascladiol (67) have been
found to exhibit no signs of toxicity towards human cell lines derived from the intestinal tract, kidney,
liver and immune system, which demonstrates that PAT (65) detoxification strategies leading to the
accumulation of ascladiols should be approaches to limit the PAT (65) risk [61]. When PAT (65) was
added in the cell cultures or cell-free supernatant of Lactobacillus plantarum, it was transformed to E-
ascladiol (66) and Z-ascladiol (67), which were further transformed into hydroascladiol (68) over a 4-
week cell-free incubation at 4 °C (Figure S31) [62].
Table 5. Other oxido-reductions of mycotoxins.
Substrate Product Biotransformation System Ref.
Aflatoxin B1
(AFB1, 1)
AFB1-8,9-epoxide (48) Channel catfish liver [20]
AFB1-8,9-dihydrodiol (49) Phanerochaete sordida YK-624 (fungus) [54]
Altertoxin II (50) Altertoxin I (52) Mammalian cell lines Caco-2, HCT 116,
HepG2, V79
[55]
Stemphyltoxin III
(51)
Alteichin (53) Mammalian cell line Caco-2 [55]
Botrydial (54) Dihydrobotrydial (55) Botrytis cinerea (fungus) [56]
Secobotrytrienediol (56) Botrytis cinerea (fungus) [56]
Citrinin (57) Dihydrocitrinone (58) Rats and humans [57]
Fomannoxin (40) Fomannoxin acid (59) Rhizosphere-associated bacterium
Streptomyces sp. AcH 505
[48]
Fomannoxin amide (60) Rhizosphere-associated bacterium
Streptomyces sp. AcH 505
[48]
MFA-1 (61) Rhizosphere-associated bacterium
Streptomyces sp. AcH 505
[48]
MFA-2 (62) Rhizosphere-associated bacterium
Streptomyces sp. AcH 505
[48]
DFA (63) Rhizosphere-associated bacterium
Streptomyces sp. AcH 505
[48]
Fusaric acid (19) Fusarinol (64) Aspergillus tubingensis (fungus) [59]
Patulin (65) E-Ascladiol (66), Z-ascladiol (67) Kodameae ohmeri (fungus) [60]
E-Ascladiol (66), Z-ascladiol (67),
hydroascladiol (68)
Lactobacillus plantarum (bacterium) [62]
Toxins 2020,12, 121 9 of 37
Toxins 2020, 12, x FOR PEER REVIEW 9 of 37
O
O
HO
62.MFA-2
OH
64. Fusarinol
N
65. Patulin
O
O
O
OH
OH
2.6. Methylation
Methylation of myctoxins was observed on the hydroxyl groups. The transformation was
catalyzed by O-methyltransferase (Table 6).
2.6. Methylation
Methylation of myctoxins was observed on the hydroxyl groups. The transformation was
catalyzed by O-methyltransferase (Table 6).
Toxins 2020,12, 121 10 of 37
Alternariol (AOH,
7
) was converted into alternariol 9-O-methyl ether (AME,
8
) by methylation
through an alternariol O-methyltranferase. The methyl donor was S-adenosyl-L-methionine (SAM)
(Figure S32) [63].
Table 6. Methylation of mycotoxins.
Substrate Product Biotransformation System Ref.
Alternariol (AOH, 7) Alternariol 9-O-methyl ether (AME, 8) Methyltransferase [64]
Zearalenone (ZEN, 33) Zearalenone 16-methyl ether (69)Cunninghamella bainieri (fungus) [38]
Zearalenone 14,16-bis (methyl ether) (70)Cunninghamella bainieri (fungus) [38]
Toxins 2020, 12, x FOR PEER REVIEW 10 of 37
Alternariol (AOH, 7) was converted into alternariol 9-O-methyl ether (AME, 8) by methylation
through an alternariol O-methyltranferase. The methyl donor was S-adenosyl-L-methionine (SAM)
(Figure S32) [63].
Zearalenone (ZEN, 33) was converted into zearalenone 16-methyl ether (69) and zearalenone
14,16-bis (methyl ether) (70) by the fungus Cunninghamella bainieri (Figure S33). Zearalenone 16-
methyl ether (69) showed similar estrogenic activity compared with the parent compound ZEN (33).
However, zearalenone 14,16-bis (methyl ether) (70) exhibited inactive estrogenic effect [38].
Table 6. Methylation of mycotoxins.
Substrate Product Biotransformation System Ref.
Alternariol (AOH, 7) Alternariol 9-O-methyl ether (AME, 8) Methyltransferase [64]
Zearalenone (ZEN, 33) Zearalenone 16-methyl ether (69) Cunninghamella bainieri (fungus) [38]
Zearalenone 14,16-bis (methyl ether) (70) Cunninghamella bainieri (fungus) [38]
2.7. Glycosylation and Glucuronidation
Glycosylation/glucuronidation of mycotoxins is the process by which a glucose or glucuronic
acid is covalently attached to a hydroxyl group (Table 7). Glycosylation/glucuronidation often
increases the polarity of mycotoxins, and reduce their toxicity. Many glycosyltransferases of
mycotoxins are present in plants. A UDP-glucosyltransferase involved in the detoxification of
deoxynivalenol was revealed from rice (Oryza sativa) [65].
Alternariol (AOH, 7) could be glycosylated into 3-O-β-D-glucopyranosyl AOH (71), 9-O-β-D-
glucopyranosyl AOH (72), 9-O-β-D-glucopyranosyl (16)-β-D-glucopyranosyl AOH (73) by
suspension cultured cells of Nicotiana tabacum (Figure S34) [66]. The suspension cultured cells of N.
tabacum had also the ability to transform alternariol 9-O-methyl ether (AME, 8) into 3-O-β-D-
glucopyranosyl AME (74) and 7-O-β-D-glucopyranosyl AME (75) through glycosylation (Figure S35)
[66]. In addition, both AOH (7) and AME (8) were metabolized to their corresponding sulfate
conjugates in cultures of Alternaria alternata. The sulfates such as AOH 3-sulfate (76), AOH 9-sulfate
(77) and AME 3-sulfate (78) were subsequently conjugated to their sulfoglucosides AOH 3-sulfate-9-
O-glucoside (79), AOH 9-sulfate-3-O-glucoside (80) and AME 3-sulfate-7-O-glucoside (81) in either
tomato tissues or tobacco cultured cells (Figure S36) [67].
Curvularin (82) is a macrocyclic lactone produced by a number of fungi from the genera
Curvularia, Penicillium and Alternaria, and have been reported to possess a variety of biological
activities including phytotoxicity [68]. Curvularin (82) was converted into curvularin 11-O-β-D-
glucopyranoside (83) and curvularin 4-O-methyl-11-O-β-D-glucopyranoside (84) with glycosylation
and methylglycosylation through the the fungus Beauveria bassiana (Figure S37) [69].
Deoxynivalenol (DON, 38) is the main trichothecene toxin produced by the Fusarium species and
a relevant virulence factor in Fusarium head blight (FHB) disease of cereal crops. Trichothecene toxins
inhibited eukaryotic protein synthesis and elicited a wide range of pathophysiological effects in
humans and animals. DON (38) could be glycosylated to DON 3-O-β-D-glucoside (D3G, 85), which
was a masked mycotoxin, by a recombinant UDP-glucosyltranferase from rice (Figure S38) [70]. DON
(38), deepoxy-deoxynivalenol (DOM, 45), iso-deoxynivalenol (iso-DON, 86) and iso-deepoxy-
deoxynivalenol (iso-DOM, 87) were respectively transformed to a series of glucuronides (8897) by
Zearalenone (ZEN,
33
) was converted into zearalenone 16-methyl ether (
69
) and zearalenone
14,16-bis (methyl ether) (
70
) by the fungus Cunninghamella bainieri (Figure S33). Zearalenone 16-methyl
ether (
69
) showed similar estrogenic activity compared with the parent compound ZEN (
33
). However,
zearalenone 14,16-bis (methyl ether) (70) exhibited inactive estrogenic eect [38].
2.7. Glycosylation and Glucuronidation
Glycosylation/glucuronidation of mycotoxins is the process by which a glucose or glucuronic acid
is covalently attached to a hydroxyl group (Table 7). Glycosylation/glucuronidation often increases the
polarity of mycotoxins, and reduce their toxicity. Many glycosyltransferases of mycotoxins are present
in plants. A UDP-glucosyltransferase involved in the detoxification of deoxynivalenol was revealed
from rice (Oryza sativa) [65].
Alternariol (AOH,
7
) could be glycosylated into 3-O-
β
-d-glucopyranosyl AOH (
71
),
9-O-
β
-d-glucopyranosyl AOH (
72
), 9-O-
β
-d-glucopyranosyl (1
6)-
β
-d-glucopyranosyl AOH (
73
)
by suspension cultured cells of Nicotiana tabacum (Figure S34) [
66
]. The suspension cultured
cells of N. tabacum had also the ability to transform alternariol 9-O-methyl ether (AME,
8
) into
3-O-
β
-d-glucopyranosyl AME (
74
) and 7-O-
β
-d-glucopyranosyl AME (
75
) through glycosylation
(Figure S35) [
66
]. In addition, both AOH (
7
) and AME (
8
) were metabolized to their corresponding
sulfate conjugates in cultures of Alternaria alternata. The sulfates such as AOH 3-sulfate (
76
), AOH
9-sulfate (
77
) and AME 3-sulfate (7
8
) were subsequently conjugated to their sulfoglucosides AOH
3-sulfate-9-O-glucoside (
79
), AOH 9-sulfate-3-O-glucoside (
80
) and AME 3-sulfate-7-O-glucoside (
81
)
in either tomato tissues or tobacco cultured cells (Figure S36) [67].
Curvularin (
82
) is a macrocyclic lactone produced by a number of fungi from the genera Curvularia,
Penicillium and Alternaria, and have been reported to possess a variety of biological activities including
phytotoxicity [
68
]. Curvularin (
82
) was converted into curvularin 11-O-
β
-d-glucopyranoside (
83
) and
curvularin 4
0
-O-methyl-11-O-
β
-d-glucopyranoside (
84
) with glycosylation and methylglycosylation
through the the fungus Beauveria bassiana (Figure S37) [69].
Deoxynivalenol (DON,
38
) is the main trichothecene toxin produced by the Fusarium species and a
relevant virulence factor in Fusarium head blight (FHB) disease of cereal crops. Trichothecene toxins
inhibited eukaryotic protein synthesis and elicited a wide range of pathophysiological effects in humans
and animals. DON (
38
) could be glycosylated to DON 3-O-
β
-d-glucoside (D3G,
85
), which was a
masked mycotoxin, by a recombinant UDP-glucosyltranferase from rice (Figure S38) [
70
]. DON (
38
),
Toxins 2020,12, 121 11 of 37
deepoxy-deoxynivalenol (DOM,
45
), iso-deoxynivalenol (iso-DON,
86
) and iso-deepoxy-deoxynivalenol
(iso-DOM,
87
) were respectively transformed to a series of glucuronides (
88
97
) by glucuronidation
through rat liver microsomes (RLM) or human liver microsomes (HLM) (Figures S39–S42) [71,72].
Both 15-monoacetoxyscirpenol (15-MAS,
98
) and 4,15-diacetoxyscirpenol (4,15-DAS,
99
) were
produced by the fungi from the genus Fusarium such as F. sporotrichioides and F. poae [
73
]. In corn plants,
both 15-MAS (
98
) and 4,15-DAS (
99
) were, respectively, transformed to 15-MAS 3-glucoside (
100
) and
4,15-DAS 3-glucoside (
101
), which were called masked mycotoxins. The structures of transformed
products (
99
and
100
) were deduced on the basis of accurate mass measurements of characteristic ions and
fragmentation patterns by using high-resolution liquid chromatography–Orbitrap mass spectrometric
analysis. Although their absolute structures were not clarified, 3-OH glucosylation appeared to be the
most probable (Figure S43) [
74
,
75
]. As the authors used Fusarium sp. infected corn material, it is not
clear whether the corn plant or the fungus itself produced the glucosides just like formation of MAS
glucoside [76] as well as the glucosides of HT-2 and MAS [77] produced by Fusarium species.
4,15-Diacetoxyscirpenol (4,15-DAS,
99
) was transformed to 4,15-DAS 3-glucuronide (
102
) with
glucuronidation in rats (Figure S44) [78].
Hydroxydestruxin B (
103
) was glycosylated into glucosyl hydroxydestruxin B (
104
) in cruciferous
plants such as Brassica napus (Figure S45) [
24
]. Fungal phytotoxin detoxification should be a resistance
mechanism of crucifers against pathogens [25].
T-2 toxin (
31
) was converted into T-2 toxin 3-O-
α
-d-glucoside (
105
) with glycosylation by the fungi
Blastobotrys muscicola and B. robertii (Figure S46) [
79
]. In animal tissures, T-2 toxin (
31
) was transformed
to T-2 toxin-3-O-
β
-d-glucuronide (T-2 GlcA,
106
) by UDP glucuronyl transferase (UDPGT) released
from rat liver microsomes (Figure S47) [80].
Zearalenone (ZEN,
33
) was glycosylated into zearalenone 14-O-glucoside (ZEN 14-O-Glc,
107
) by
Arabidopsis UDP-glucosyltransferases expressed in Saccharomyces cerevisiae (Figure S48) [
81
]. Similarly,
ZEN (
33
) was converted to ZEN 14-O-Glc (
107
) with glycosylation by the fungi Mucor vainieri and
Thamnidium elegans [
82
]. ZEN (
33
) was simultaneously glycosylated into ZEN 14-O-Glc (
107
) and
zearalenone 16-O-glucoside (ZEN 16-O-Glc,
108
) by a barley UDP-glucosyltransferase expressed
in Saccharomyces cerevisiae (Figure S49) [
83
]. The monoglucosides (i.e., ZEN 14-O-Glc and ZEN
16-O-Glc) could be further transformed to ZEN 14,16-di-glucoside (
109
) by the recombinant barley
glucosyltransferase (Figure S50) [84].
Table 7. Glycosylation and glucuronidation of mycotoxins.
Substrate Product Biotransformation System Ref.
Alternariol (AOH, 7) 3-O-β-d-Glucopyranosyl alternariol (71) Suspension cell cultures of
Nicotiana tabacum
[66]
9-O-β-d-Glucopyranosyl alternariol (72) Suspension cell cultures of
Nicotiana tabacum
[66]
9-O-β-d-Glucopyranosyl
(16)-β-d-glucopyranosyl
alternariol (73)
Suspension cell cultures of
Nicotiana tabacum
[66]
Alternariol 9-O-methyl
ether (AME, 8)
3-O-β-d-Glucopyranosyl AME (74) Suspension cell cultures of
Nicotiana tabacum
[66]
7-O-β-d-Glucopyranosyl AME (75) Suspension cell cultures of
Nicotiana tabacum
[66]
AOH 3-sulfate (76) AOH 3-sulfate 9-O-glucoside (79) Tomato tissues and cultured
tobacco cells
[67]
AOH 9-sulfate (77) AOH 9-sulfate 3-O-glucoside (80) Tomato tissues and cultured
tobacco cells
[67]
AME 3-sulfate (78) AME 3-sulfate 7-O-glucoside (81) Tomato tissues and cultured
tobacco cells
[67]
Curvularin (82) Curvularin 11-O-β-d-glucopyranoside
(83)
Beauveria bassiana (fungus) [69]
Toxins 2020,12, 121 12 of 37
Table 7. Cont.
Substrate Product Biotransformation System Ref.
Curvularin
4‘-O-methyl-11-O-β-d-glucopyranoside
(84)
Beauveria bassiana (fungus) [69]
Deoxynivalenol (DON, 38) DON 3-O-β-d-glucoside (85) A combinant
UDP-gluosyltransferase from rice
[70]
DON-3-GlcA (88) Rat liver microsomes (RLM),
human liver microsomes (HLM)
[71]
DON-15-GlcA (89) RLM, HLM [71]
Deepoxy-deoxynivalenol
(DOM, 45)
DOM-3-GlcA (90) RLM, HLM [71]
DOM-15-GlcA (91) RLM, HLM [71]
Iso-DON (86) Iso-DON-3-GlcA (92) RLM, HLM [71]
Iso-DON-8-GlcA (93) RLM [71]
Iso-DON-15-GlcA (94) RLM, HLM [71]
Iso-DOM (87) Iso-DOM-3-GlcA (95) RLM, HLM [71]
Iso-DOM-8-GlcA (96) RLM [71]
Iso-DOM-15-GlcA (97) RLM, HLM [71]
15-Monoacetoxyscirpenol
(15-MAS, 98)
15-MAS 3-glucoside (100) Corn (Zea Mays) plants [75]
4,15-Diacetoxyscirpenol
(4,15-DAS, 99)
4,15-DAS 3-glucoside (101) Corn (Zea Mays) plants [75]
4,15-DAS 3-Glucuronide (102) Rats [78]
Hydroxydestruxin B (103) Glucosyl hydroxydestruxin B (104) Crucifers such as Brassica napus [24]
T-2 toxin (31) T-2 toxin 3-O-α-d-glucoside (105) Fungi Blastobotrys muscicola,B.
robertii
[79]
T-2 toxin 3-O-glucuronide (T-2 GlcA,
106)
Rat hepatic microsomes [80]
Zearalenone (ZEN, 33) ZEN 14-O-glucoside (107)Arabidopis
UDP-glucosyltransferase
[81]
Mucor bainieri (fungus) [82]
Thamnidium elegans (fungus) [82]
Barley UDP-glucosyltransferase [83]
ZEN 16-O-glucoside (108) Barley UDP-glucosyltransferase [83]
ZEN 14,16-di-glucoside (109) Recombinant barley
glucosyltransferase
[84]
Toxins 2020, 12, x FOR PEER REVIEW 12 of 37
Deoxynivalenol
(DON, 38)
DON 3-O-β-D-glucoside (85) A combinant UDP-gluosyltransferase
from rice
[70]
DON-3-GlcA (88) Rat liver microsomes (RLM), human
liver microsomes (HLM)
[71]
DON-15-GlcA (89) RLM, HLM [71]
Deepoxy-
deoxynivalenol
(DOM, 45)
DOM-3-GlcA (90) RLM, HLM [71]
DOM-15-GlcA (91) RLM, HLM [71]
Iso-DON (86) Iso-DON-3-GlcA (92) RLM, HLM [71]
Iso-DON-8-GlcA (93) RLM [71]
Iso-DON-15-GlcA (94) RLM, HLM [71]
Iso-DOM (87) Iso-DOM-3-GlcA (95) RLM, HLM [71]
Iso-DOM-8-GlcA (96) RLM [71]
Iso-DOM-15-GlcA (97) RLM, HLM [71]
15-
Monoacetoxyscirpen
ol (15-MAS, 98)
15-MAS 3-glucoside (100) Corn (Zea Mays) plants [75]
4,15-
Diacetoxyscirpenol
(4,15-DAS, 99)
4,15-DAS 3-glucoside (101) Corn (Zea Mays) plants [75]
4,15-DAS 3-Glucuronide (102) Rats [78]
Hydroxydestruxin B
(103)
Glucosyl hydroxydestruxin B (104) Crucifers such as Brassica napus [24]
T-2 toxin (31) T-2 toxin 3-O-α-D-glucoside (105) Fungi Blastobotrys muscicola, B. robertii [79]
T-2 toxin 3-O-glucuronide (T-2
GlcA, 106)
Rat hepatic microsomes [80]
Zearalenone (ZEN,
33)
ZEN 14-O-glucoside (107) Arabidopis UDP-glucosyltransferase [81]
Mucor bainieri (fungus) [82]
Thamnidium elegans (fungus) [82]
Barley UDP-glucosyltransferase [83]
ZEN 16-O-glucoside (108) Barley UDP-glucosyltransferase [83]
ZEN 14,16-di-glucoside (109) Recombinant barley glucosyltransferase [84]
Toxins 2020,12, 121 13 of 37
Toxins 2020, 12, x FOR PEER REVIEW 13 of 37
2.8. Esterification
Esterification of mycotoxins is a reaction to form ester mainly from alcohols and carboxylic acids
(Table 8). Ochratoxin A (OTA, 21) was converted to OTA methyl ester (110) by the cell cultures of
wheat and maize (Figure S51) [31].
T-2 toxin (31) was converted to 3-acetyl T-2 toxin (111) with acetylation by bovine rumen fluid
in vitro (Figure S52) [85].
Table 8. Esterification of mycotoxins.
Substrate Product Biotransformation System Ref.
Ochratoxin A (21) Ochratoxin A methyl ester (110) Cell cultures of wheat and maize [31]
T-2 toxin (31) 3-Acetyl T-2 toxin (111) Bovine rumen fluid in vitro [85]
2.8. Esterification
Esterification of mycotoxins is a reaction to form ester mainly from alcohols and carboxylic acids
(Table 8). Ochratoxin A (OTA,
21
) was converted to OTA methyl ester (
110
) by the cell cultures of
wheat and maize (Figure S51) [31].
T-2 toxin (
31
) was converted to 3-acetyl T-2 toxin (
111
) with acetylation by bovine rumen fluid
in vitro (Figure S52) [85].
Table 8. Esterification of mycotoxins.
Substrate Product Biotransformation System Ref.
Ochratoxin A (21) Ochratoxin A methyl ester (110)
Cell cultures of wheat and maize
[31]
T-2 toxin (31) 3-Acetyl T-2 toxin (111) Bovine rumen fluid in vitro [85]
Toxins 2020, 12, x FOR PEER REVIEW 13 of 37
2.8. Esterification
Esterification of mycotoxins is a reaction to form ester mainly from alcohols and carboxylic acids
(Table 8). Ochratoxin A (OTA, 21) was converted to OTA methyl ester (110) by the cell cultures of
wheat and maize (Figure S51) [31].
T-2 toxin (31) was converted to 3-acetyl T-2 toxin (111) with acetylation by bovine rumen fluid
in vitro (Figure S52) [85].
Table 8. Esterification of mycotoxins.
Substrate Product Biotransformation System Ref.
Ochratoxin A (21) Ochratoxin A methyl ester (110) Cell cultures of wheat and maize [31]
T-2 toxin (31) 3-Acetyl T-2 toxin (111) Bovine rumen fluid in vitro [85]
Toxins 2020,12, 121 14 of 37
2.9. Hydrolysis
Both ester and amide bonds of mycotoxins were widely investigated for hydrolysis
(Table 9) [79,80,86,87]
. A crude cell-free extract from cultures of Fusairum sp. strain C37410-90
possessed significant esterase activity and hydrolyzed the 3-acetyl deoxynivalenol (3-acetyl DON,
112
)
to DON (
38
) (Figure S53) [
88
]. This de-acetylation was also found in the fungus Sphaerodes mycoparasitica
incubated with 3-acetyl DON (112) [87].
4,15-Diacetoxyscirpenol (4,15-DAS,
99
) is a potent mycotoxin produced by some Fusarium species.
4,15-DAS (
99
) was hydrolyzed to either 4-monoacetoxyscirpenol (4-MAS,
113
) or 15-monoacetoxyscirpenol
(15-MAS,
98
), and the final product was scirpentriol (SCP,
114
) with deacetylation in rats (Figure S54) [
78
].
Fumunisin B
1
(FB
1
,
115
) was transformed to the hydrolyzed FB
1
namely aminopentol 1 (AP1,
116
), with hydrolysis by the fungus Exophiala spinifera 2141.10 (Figure S55) [
89
]. FB
1
(
115
) was also
converted to AP1 (
116
) either with the enzyme from the bacterium Sphingopyxis sp. MTA144 [
90
] or
with carboxylesterase FumD [91].
Fusarenon-X (FX,
117
) was hydrolyzed into nivalenol (NIV,
46
) via deacetylation in mice [
92
] and
goat (Capra hircus) [
93
] excreted mainly in urine (Figure S56). The liver and kidney are the organs
responsible for the conversion of FX (117) to NIV (46).
The crude lipase from Aspergillus niger was screened to degrade ochratoxin A (OTA,
21
) to nontoxic
OT
α
(
118
) and L-
β
-phenylalanine (
119
) (Figure S57) among 23 commercial hydrolases [
94
]. Other
active enzymes having the same conversion included protease A, prolyve PAC and pancreatin [
95
],
as well as carboxypeptidase A [
96
]. In addition, OTA (
21
) was found to be hydrolyzed to OT
α
(
118
)
and L-β-phenylalanine (119) by Aspergillus niger [97] and Bacillus amyloliquefaciens [98].
OTA (
21
) was converted into a lactone-opened ochratoxin A (OP-OTA,
120
), which was named
N-[3-carboxy-5-chloro-2-hydroxy-4-(2-hydroxypropyl) benzoyl]-L-phenylalanine (Figure S58) [
99
].
OP-OTA (
120
) was tested to be more toxic than the parent molecule which indicated that the lactone
ring was not considered to be responsible for the toxic activity of OTA (21) [16].
Ochratoxin C (OTC,
121
), which was also called OTA ethyl ester, was hydrolyzed into OTA (
21
) by
deacetylation in rats after oral and intravenous administration (Figure S59). The very fast conversion
of OTC (121) into OTA (21) is a possible explanation of the similar toxicity of ocratoxins A (21) and C
(121) to animals and humans [100].
T-2 toxin (
31
) was selectively hydrolyzed at C-4 by the bacterium Eubacterium BBSH 797, giving
rise to HT-2 toxin (
122
) as the only metabolite (Figure S60) [
86
]. The previous study on the metabolism
of T-2 toxin (
31
) in livers of rabbits, rats, guinea pigs and mice also showed that T-2 toxin (
31
) was only
hydrolyzed at C-4 to HT-2 toxin (122) by deacetylation [101].
In the rat liver and intestines, T-2 toxin (
31
) was first hydrolyzed into HT-2 toxin (
122
), which
was further converted to 15-acety-tetraol (
123
), which was finally transformed to T-2 tetraol (
124
) with
hydrolyzation (Figure S61) [102].
In addition, T-2 toxin (
31
) was selectively hydrolyzed at C-8 resulting in the removal of isovaleryl
group by the fungus Blastobotrys capitulate to neosolaniol (125) (Figure S62) [79].
Table 9. Hydrolysis of mycotoxins.
Substrate Product Biotransformation System Ref.
3-Acetyl DON (112) DON (38) Cell-free extracts of the fungus
Fusarium sp.
[88]
Sphaerodes mycoparasitica (fungus) [87]
4,15-Diacetoxyscirpenol
(4,15-DAS, 99)
4-Monoacetoxyscirpenol
(4-MAS, 113)
Rats [78]
15-Monoacetoxyscirpenol
(15-MAS, 98)
Rats [78]
Scirpentriol (SCP, 114) Rats [78]
Toxins 2020,12, 121 15 of 37
Table 9. Cont.
Substrate Product Biotransformation System Ref.
Fumonisin B1(115) Hydrolyzed fumonisin B1=
Aminopentol 1 (AP1, 116)
Exophiala spinifera 2141.10 (fungus) [89]
Hydroxylase from the bacterium
Sphingopyxis sp. MTA144
[90]
Carboxylesterase FumD [91]
Fusarenon-X (FX, (117) Nivalenol (NIV, 46) Mice [92]
Goat (Capra hircus) [93]
Ochratoxin A (OTA, 21) Ochratoxin α(118) and
L-β-phenylalanine (119)
Crude lipase from Aspergillus niger [94]
Protease A prolyve PAC and
pancreatin [95]
Carboxypeptidase A [96]
Fungus: Aspergillus niger (fungus) [97]
Bacillus amyloliquefaciens (bacterium)
[98]
Lactone-opened ochratoxin
A (OP-OTA, 120)Rats [99]
Ochratoxin C (OTC) =
Ochratoxin A ethyl ester
(121)
Ochratoxin A (OTA, 21) Rats [100]
T-2 toxin (31) HT-2 toxin (122)Eubacterium BBSH 797 (bacterium) [86]
HT-2 toxin
(122),15-acetyl-tetraol
(123),T-2 tetraol (124)
Liver and intestines of rats [102]
Neosolaniol (125)Blastobotrys capitulate (fungus) [79]
Toxins 2020, 12, x FOR PEER REVIEW 15 of 37
Hydroxylase from the
bacterium Sphingopyxis sp.
MTA144
[90]
Carboxylesterase FumD [91]
Fusarenon-X (FX, (117) Nivalenol (NIV, 46) Mice [92]
Goat (Capra hircus) [93]
Ochratoxin A (OTA, 21) Ochratoxin α (118) and L-β-
phenylalanine (119)
Crude lipase from Aspergillus
niger [94]
Protease A prolyve PAC and
pancreatin [95]
Carboxypeptidase A [96]
Fungus: Aspergillus niger
(fungus)
[97]
Bacillus amyloliquefaciens
(bacterium)
[98]
Lactone-opened ochratoxin A
(OP-OTA, 120) Rats [99]
Ochratoxin C (OTC) =
Ochratoxin A ethyl ester (121)
Ochratoxin A (OTA, 21) Rats [100]
T-2 toxin (31) HT-2 toxin (122) Eubacterium BBSH 797
(bacterium)
[86]
HT-2 toxin (122),
15-acetyl-tetraol (123),
T-2 tetraol (124)
Liver and intestines of rats [102]
Neosolaniol (125) Blastobotrys capitulate (fungus) [79]
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2.10. Sulfation
Sulfation of mycotoxins is the sulfotransferase-catalyzed conjugation of a sulfo group on a
hydroxyl group (Table 10). Both deoxynivalenol (DON, 38) and zearalenone (ZEN, 33) were
converted to their corresponding sulfates DON 3-sulfate (126) and ZEN 14-sulfate (127) (Figure S63)
by the fungus Sphaerodes mycoparasitica [87]. ZEN (33) was also found to be converted to ZEN 14-
sulfate (127) by pigs [103]. Both DON 3-sulfate (126) and ZEN 14-sulfate (127) were less toxic than
DON (38) and ZEN (33), respectively [87].
Table 10. Sulfation of mycotoxins.
Substrate Product Biotransformation System Ref.
Deoxynivalenol (38) Deoxynivlenol 3-sulfate (126) Sphaerodes mycoparasitica (fungus) [87]
Zearalenone (33) Zearalenone 14-sulfate (127) Sphaerodes mycoparasitica (fungus) [87]
Pigs [103]
2.11. Demethylation
Demethylation of mycotoxins is the process resulting in the removal of a methyl group from a
molecule (Table 11). A common way of mycotoxin demethylation is replacement of a methoxyl group
by a hydroxyl group. Alternariol 9-O-methyl ether (AME, 8) was converted to alternariol (AOH, 7)
with demethylation by the homogenate of porcine liver in the presence of NADPH (Figure S64) [104].
Aflatoxin B1 (AFB1, 1) was converted to aflatoxin P1 (AFP1, 128) with demethylation by the
enzyme CYP321A1 from corn earworm Helicoverpa zea (Figure S65). AFP1 (128) was more polar and
less toxic than AFB1 (1) [105].
Table 11. Demethylation of mycotoxins.
Substrate Product Biotransformation System Ref.
AME (8) AOH (7) Homogenate of porcine liver in the presence of NADPH [104]
AFB1 (1) Aflatoxin P1 (AFP1, 128) Enzyme CYP321A1 from Helicoverpa zea [105]
2.10. Sulfation
Sulfation of mycotoxins is the sulfotransferase-catalyzed conjugation of a sulfo group on a
hydroxyl group (Table 10). Both deoxynivalenol (DON,
38
) and zearalenone (ZEN,
33
) were converted
to their corresponding sulfates DON 3-sulfate (
126
) and ZEN 14-sulfate (
127
) (Figure S63) by the fungus
Sphaerodes mycoparasitica [
87
]. ZEN (
33
) was also found to be converted to ZEN 14-sulfate (
127
) by
pigs [
103
]. Both DON 3-sulfate (
126
) and ZEN 14-sulfate (
127
) were less toxic than DON (
38
) and ZEN
(33), respectively [87].
Table 10. Sulfation of mycotoxins.
Substrate Product Biotransformation System Ref.
Deoxynivalenol (38) Deoxynivlenol 3-sulfate (126)Sphaerodes mycoparasitica (fungus) [87]
Zearalenone (33) Zearalenone 14-sulfate (127)Sphaerodes mycoparasitica (fungus) [87]
Pigs [103]
Toxins 2020, 12, x FOR PEER REVIEW 16 of 37
2.10. Sulfation
Sulfation of mycotoxins is the sulfotransferase-catalyzed conjugation of a sulfo group on a
hydroxyl group (Table 10). Both deoxynivalenol (DON, 38) and zearalenone (ZEN, 33) were
converted to their corresponding sulfates DON 3-sulfate (126) and ZEN 14-sulfate (127) (Figure S63)
by the fungus Sphaerodes mycoparasitica [87]. ZEN (33) was also found to be converted to ZEN 14-
sulfate (127) by pigs [103]. Both DON 3-sulfate (126) and ZEN 14-sulfate (127) were less toxic than
DON (38) and ZEN (33), respectively [87].
Table 10. Sulfation of mycotoxins.
Substrate Product Biotransformation System Ref.
Deoxynivalenol (38) Deoxynivlenol 3-sulfate (126) Sphaerodes mycoparasitica (fungus) [87]
Zearalenone (33) Zearalenone 14-sulfate (127) Sphaerodes mycoparasitica (fungus) [87]
Pigs [103]
2.11. Demethylation
Demethylation of mycotoxins is the process resulting in the removal of a methyl group from a
molecule (Table 11). A common way of mycotoxin demethylation is replacement of a methoxyl group
by a hydroxyl group. Alternariol 9-O-methyl ether (AME, 8) was converted to alternariol (AOH, 7)
with demethylation by the homogenate of porcine liver in the presence of NADPH (Figure S64) [104].
Aflatoxin B1 (AFB1, 1) was converted to aflatoxin P1 (AFP1, 128) with demethylation by the
enzyme CYP321A1 from corn earworm Helicoverpa zea (Figure S65). AFP1 (128) was more polar and
less toxic than AFB1 (1) [105].
Table 11. Demethylation of mycotoxins.
Substrate Product Biotransformation System Ref.
AME (8) AOH (7) Homogenate of porcine liver in the presence of NADPH [104]
AFB1 (1) Aflatoxin P1 (AFP1, 128) Enzyme CYP321A1 from Helicoverpa zea [105]
2.11. Demethylation
Demethylation of mycotoxins is the process resulting in the removal of a methyl group from a
molecule (Table 11). A common way of mycotoxin demethylation is replacement of a methoxyl group
by a hydroxyl group. Alternariol 9-O-methyl ether (AME,
8
) was converted to alternariol (AOH,
7
)
with demethylation by the homogenate of porcine liver in the presence of NADPH (Figure S64) [
104
].
Aflatoxin B
1
(AFB
1
,
1
) was converted to aflatoxin P
1
(AFP
1
,
128
) with demethylation by the
enzyme CYP321A1 from corn earworm Helicoverpa zea (Figure S65). AFP
1
(
128
) was more polar and
less toxic than AFB1(1) [105].
Table 11. Demethylation of mycotoxins.
Substrate Product Biotransformation System Ref.
AME (8) AOH (7) Homogenate of porcine liver in the presence
of NADPH
[104]
AFB1(1) Aflatoxin P1(AFP1,128) Enzyme CYP321A1 from Helicoverpa zea [105]
Toxins 2020,12, 121 17 of 37
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2.12. Deamination
Deamination of mycotoxins is the removal of an amino group from a molecule catalyzed by the
deaminase (Table 12). Fumonisin B4 (FB4, 129) was transformed into fumonisins La4 (Fla4, 130) and
Py4 (FPy4, 131) through oxidative deamination by Aspergillus sp. (Figure S66) [106]. Using a duckweed
(Lemna minor) bioassay, both Fla4 (130) and FPy4, (131) were significantly less toxic in comparision to
the fumonisin B mycotoxins. This demonstrated that Aspergillus fungi have the ability to produce
enzymes that could be used for fumonisin detoxification [106].
Hydrolyzed fumonisin B1 (HFB1, 116), which was also named as aminopentol 1 (AP1), was
converted into 2-keto HFB1 (132) or namely 2-keto AP1 through oxidative deamination by the fungus
Exophiala spinifera (Figure S67) [107].
Table 12. Deamination of mycotoxins.
Substrate Product
Biotransformation
System Ref.
Fumonisin B4 (129) Fumonisin La4 (FLa4, 130) Aspergillus sp. (fungus) [106]
Fumonisin Py4 (FPy4, 131) Aspergillus sp. (fungus) [106]
Hydrolyzed fumonisin B1 = Aminopentol 1
(AP1, 116)
2-Keto HFB1 = 2-keto AP1
(132)
Exophiala spinifera
(fungus)
[107]
2.12. Deamination
Deamination of mycotoxins is the removal of an amino group from a molecule catalyzed by the
deaminase (Table 12). Fumonisin B
4
(FB
4
,
129
) was transformed into fumonisins La
4
(Fla
4
,
130
) and
Py
4
(FPy
4
,
131
) through oxidative deamination by Aspergillus sp. (Figure S66) [
106
]. Using a duckweed
(Lemna minor) bioassay, both Fla
4
(
130
) and FPy
4
, (
131
) were significantly less toxic in comparision
to the fumonisin B mycotoxins. This demonstrated that Aspergillus fungi have the ability to produce
enzymes that could be used for fumonisin detoxification [106].
Hydrolyzed fumonisin B
1
(HFB
1
,
116
), which was also named as aminopentol 1 (AP1), was
converted into 2-keto HFB
1
(
132
) or namely 2-keto AP1 through oxidative deamination by the fungus
Exophiala spinifera (Figure S67) [107].
Table 12. Deamination of mycotoxins.
Substrate Product Biotransformation System Ref.
Fumonisin B4(129) Fumonisin La4(FLa4,130)Aspergillus sp. (fungus) [106]
Fumonisin Py4(FPy4,131)Aspergillus sp. (fungus) [106]
Hydrolyzed fumonisin B1=
Aminopentol 1 (AP1, 116)
2-Keto HFB1=2-keto AP1 (132)Exophiala spinifera (fungus) [107]
Toxins 2020, 12, x FOR PEER REVIEW 17 of 37
2.12. Deamination
Deamination of mycotoxins is the removal of an amino group from a molecule catalyzed by the
deaminase (Table 12). Fumonisin B4 (FB4, 129) was transformed into fumonisins La4 (Fla4, 130) and
Py4 (FPy4, 131) through oxidative deamination by Aspergillus sp. (Figure S66) [106]. Using a duckweed
(Lemna minor) bioassay, both Fla4 (130) and FPy4, (131) were significantly less toxic in comparision to
the fumonisin B mycotoxins. This demonstrated that Aspergillus fungi have the ability to produce
enzymes that could be used for fumonisin detoxification [106].
Hydrolyzed fumonisin B1 (HFB1, 116), which was also named as aminopentol 1 (AP1), was
converted into 2-keto HFB1 (132) or namely 2-keto AP1 through oxidative deamination by the fungus
Exophiala spinifera (Figure S67) [107].
Table 12. Deamination of mycotoxins.
Substrate Product
Biotransformation
System Ref.
Fumonisin B4 (129) Fumonisin La4 (FLa4, 130) Aspergillus sp. (fungus) [106]
Fumonisin Py4 (FPy4, 131) Aspergillus sp. (fungus) [106]
Hydrolyzed fumonisin B1 = Aminopentol 1
(AP1, 116)
2-Keto HFB1 = 2-keto AP1
(132)
Exophiala spinifera
(fungus)
[107]
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2.13. Miscellaneous Reactions
Many other types of biotransformation of mycotoxins have also been reported, such as
epimerization, epoxidation, dehydrogenation, dechlorination and their multi-step conversions (Table
13).
Aflatoxin B1 (AFB1, 1) was converted to dihydrohydroxyaflatoxin B1 (133), which was also
named as aflatoxin B2a (AFB2a), via reduction and oxidation by Pleurotus ostreatus GHBBF10 (Figure
S68) [108].
AFB1 (1) was detoxified to aflatoxin D1 (AFD1, 134), aflatoxin D2 (AFD2, 135) and aflatoxin D3
(AFD3, 136) through hydrolysis, decarboxylation, and oxidation-reduction by Pseudomonas putida,
which was isolated from sugarcane (Figure S69). The conversion mechanism from AFB1 (1) to AFD1
(134) was also entirely elucidated [109]. Cytotoxicity study clearly implied that AFD1 (134) was non-
toxic, and both AFD2 (135) and AFD3 (136) were much less toxic by comparing with AFB1 (1) [110].
Alternariol (AOH, 7) was transformed to 3-O-(6-O-malonyl-β-D-glucopyranosyl) AOH (137) and
9-O-(6-O-malonyl-β-D-glucopyranosyl) AOH (138) through glycosylation and esterification by the
cell cultures of Nicotiana tabacum (Figure S70) [66]. Similarly, alternariol 9-O-methyl ether (AME, 8)
was also transformed to 3-O-(4-O-malonyl-β-D-glucopyranosyl) AME (139) and 3-O-(6-O-malonyl-β-
D-glucopyranosyl) AME (140) with glycosylation and esterificationby by the suspension cell cultures
of Nicotiana tabacum (Figure S71) [66]
Botrydial (54) was converted into botryenedial (141) with dehydration by the fungus Botrytis
cinerea (Figure S72). Botryenedial (141) was less phytotoxic than botrydial (54) [56].
Citrinin (CTN, 57) was first identified as an antibiotic. It was also considered as a mycotoxin to
damage DNA. CTN (57) was converted to decarboxycitrinin (142) with decarboxylation by the
bacterium Moraxella sp. MB1 (Figure S73) [111]. Decarboxycitrinin (142) was also the product of heat
treatment of CTN (57), and retained antibiotic activity, but was not toxic to mice [112].
Deoxynivalenol (DON, 38) was converted into 3-epi-deoxynivalenol (143) (Figure S74) with
epimerization by Nocardioides sp. WSN05-2 [113], and Devosia sp. [114]. It was known that DON (38)
epimerization proceeded through the formation of 3-keto-DON (39) intermediate to convert to 3-epi-
deoxynivalenol (143) by a two-step biocatalysis [115].
When deoxynivalenol (DON, 38) was incubated with rat liver microsomes (RLM), the isomer
iso-DON (86) was formed with isomerization [71]. Iso-DON (86), which was less toxic than DON (38),
was also found to be converted from DON (38) under harsh condition non-enzymatically [116]. Other
transformed products included iso-DON-3-GlcA (92), iso-DON-8-GlcA (93) and DON-8,15-
hemiketal-8-GlcA (144) (Figures S75 and S76) [71]. When deepoxy-deoxynivalenol (DOM, 45) was
incubated with RLM, iso-DOM (87), iso-DOM-3-GlcA (95) and iso-DOM-8-GlcA (96) were
transformed with isomerization and glucuronization (Figure S77) [71].
When fomannoxin (40) was added in the cell cultures of Pinus sylvestris, formannoxin (40) was
transformed into the non-toxic fomannoxin acid (59), which was further glycosylated to fomannoxin
acid β-glucoside (145) with time prolonging (Figure S78) [44].
Degradation transformation of fumonisin B1 (115) comprises at least two enzymatic steps, an
initial hydrolysis (deesterification reaction) to form aminopentol 1 (AP1, 116), followed by
deamination of AP1 (116) to form 2-keto AP1 (132). Two recombinant enzymes carboxylesterase and
aminotransferase from the bacterium Sphingopyxis sp. were expressed heterologously.
Carboxylesterase catalyzed fumonisin B1 (115) to AP1 (116) with deesterification (Figure S79).
Aminotransferase catalyzed AP1 (116) to 2-keto AP1 (132) with deamination in the presence of
pyruvate and pyridoxal phosphate [90].
2.13. Miscellaneous Reactions
Many other types of biotransformation of mycotoxins have also been reported, such as
epimerization, epoxidation, dehydrogenation, dechlorination and their multi-step conversions
(Table 13).
Aflatoxin B
1
(AFB
1
,
1
) was converted to dihydrohydroxyaflatoxin B
1
(
133
), which was also named
as aflatoxin B
2a
(AFB
2a
), via reduction and oxidation by Pleurotus ostreatus GHBBF10 (Figure S68) [
108
].
AFB
1
(
1
) was detoxified to aflatoxin D
1
(AFD
1
,
134
), aflatoxin D
2
(AFD
2
,
135
) and aflatoxin D
3
(AFD
3
,
136
) through hydrolysis, decarboxylation, and oxidation-reduction by Pseudomonas putida,
which was isolated from sugarcane (Figure S69). The conversion mechanism from AFB
1
(
1
) to AFD
1
(
134
) was also entirely elucidated [
109
]. Cytotoxicity study clearly implied that AFD
1
(
134
) was
non-toxic, and both AFD
2
(
135
) and AFD
3
(
136
) were much less toxic by comparing with AFB
1
(
1
) [
110
].
Alternariol (AOH,
7
) was transformed to 3-O-(6-O-malonyl-
β
-d-glucopyranosyl) AOH (
137
)
and 9-O-(6-O-malonyl-
β
-d-glucopyranosyl) AOH (
138
) through glycosylation and esterification
by the cell cultures of Nicotiana tabacum (Figure S70) [
66
]. Similarly, alternariol 9-O-methyl
ether (AME,
8
) was also transformed to 3-O-(4-O-malonyl-
β
-d-glucopyranosyl) AME (
139
) and
3-O-(6-O-malonyl-
β
-d-glucopyranosyl) AME (
140
) with glycosylation and esterificationby by the
suspension cell cultures of Nicotiana tabacum (Figure S71) [66]
Botrydial (
54
) was converted into botryenedial (
141
) with dehydration by the fungus Botrytis
cinerea (Figure S72). Botryenedial (141) was less phytotoxic than botrydial (54) [56].
Citrinin (CTN,
57
) was first identified as an antibiotic. It was also considered as a mycotoxin
to damage DNA. CTN (
57
) was converted to decarboxycitrinin (
142
) with decarboxylation by the
bacterium Moraxella sp. MB1 (Figure S73) [111]. Decarboxycitrinin (142) was also the product of heat
treatment of CTN (57), and retained antibiotic activity, but was not toxic to mice [112].
Deoxynivalenol (DON,
38
) was converted into 3-epi-deoxynivalenol (
143
) (Figure S74) with
epimerization by Nocardioides sp. WSN05-2 [
113
], and Devosia sp. [
114
]. It was known that DON
(
38
) epimerization proceeded through the formation of 3-keto-DON (
39
) intermediate to convert to
3-epi-deoxynivalenol (143) by a two-step biocatalysis [115].
When deoxynivalenol (DON,
38
) was incubated with rat liver microsomes (RLM), the
isomer iso-DON (
86
) was formed with isomerization [
71
]. Iso-DON (
86
), which was less
toxic than DON (
38
), was also found to be converted from DON (
38
) under harsh condition
non-enzymatically [
116
]. Other transformed products included iso-DON-3-GlcA (
92
), iso-DON-8-GlcA
(
93
) and DON-8,15-hemiketal-8-GlcA (
144
) (Figures S75 and S76) [
71
]. When deepoxy-deoxynivalenol
(DOM,
45
) was incubated with RLM, iso-DOM (
87
), iso-DOM-3-GlcA (
95
) and iso-DOM-8-GlcA (
96
)
were transformed with isomerization and glucuronization (Figure S77) [71].
When fomannoxin (
40
) was added in the cell cultures of Pinus sylvestris, formannoxin (
40
) was
transformed into the non-toxic fomannoxin acid (
59
), which was further glycosylated to fomannoxin
acid β-glucoside (145) with time prolonging (Figure S78) [44].
Degradation transformation of fumonisin B
1
(
115
) comprises at least two enzymatic steps, an initial
hydrolysis (deesterification reaction) to form aminopentol 1 (AP1,
116
), followed by deamination of
AP1 (
116
) to form 2-keto AP1 (
132
). Two recombinant enzymes carboxylesterase and aminotransferase
from the bacterium Sphingopyxis sp. were expressed heterologously. Carboxylesterase catalyzed
fumonisin B
1
(
115
) to AP1 (
116
) with deesterification (Figure S79). Aminotransferase catalyzed AP1
(
116
) to 2-keto AP1 (
132
) with deamination in the presence of pyruvate and pyridoxal phosphate [
90
].
Toxins 2020,12, 121 19 of 37
Ochratoxin (OTA,
21
) was hydroxylated into (4R)-4-hydroxyochratoxin A (
24
) and (4S)-4-
hydroxyochratoxin A (
25
), which were further glycosylated and esterified, respectively, by
the cell cultures of wheat and maize to (4R)-4-hydroxyochratoxin A methyl ester (
146
),
(4S)-4-hydroxyochratoxin A methyl ester (
147
), (4R)-4-hydroxyochratoxin A 4-O-
β
-d-glucoside (
148
)
and (4S)-4-hydroxyochratoxin A 4-O-
β
-d-glucoside (
149
) (Figure S80) [
31
]. OTA (
21
) was dechlorinated
into ochratoxin B (OTB,
27
) in the renal microsomes of rabbits pretreated with phenobarbital (PB). OTB
(27) was less toxic than OTA (21) (Figure S81) [117].
Patulin (PAT,
65
) was transformed to desoxypatulinic acid (DPA,
150
) with multi-step reactions
(Figure S82) by the fungi Rhodotorula kratochvilovae [
118
] and Rhodosporidium paludigenum [
119
].
Conversion of PAT (
65
) to the less toxic desoxypatulinic acid (
150
) was considered a detoxification
process [120].
Zearalenone (ZEN,
33
) was transformed to
α
-zearalenol (
42
),
β
-zearalenol (
43
),
α
-zearalanol (
151
),
β
-zearalanol (
152
) and zearalanone (
44
) with multi-step oxido-reductions in human body (Figure
S83) [
121
]. In addition, ZEN (
33
) was converted to hydrolyzed ZEN (
155
) through hydrolysis, and then
to decarboxylated hydrolyzed ZEN (
156
) through spontaneous decarboxylation by Bacillus pumilus
(Figure S84) [
122
]. Similar biotransformation of ZEN (
33
) was also observed by using a lactonase
named ZHD101 from Clonostachys rosea [123,124].
Table 13. Miscellaneous biotransformation of mycotoxins.
Substrate Product Type Biotransformation System Ref.
Aflatoxin B
1
(AFB
1
,
1
)
Dihydrohydroxyalfatoxin B1
(AFB2a,133)
Reduction and oxidation Pleurotus ostreatus (fungus) [86]
AFD1(134), AFD2(135), and
AFD3(136)
Hydolysis,
decarboxylation,
oxidation-reduction
Pseudomonas putida
(bacterium)
[110]
Alternariol (AOH, 7) 3-O-(6-O-Malonyl-β-d-
glucopyranosyl) AOH (137)
Glycosylation and
Esterification
Suspension cell cultures of
Nicotiana tabacum
[66]
9-O-(6-O-Malonyl-β-d-
glucopyranosyl) AOH (138)
Glycosylation and
Esterification
Suspension cell cultures of
Nicotiana tabacum
[66]
Alternariol
9-O-methyl ether =
AME (8)
3-O-(4-O-Malonyl-β-d-
glucopyranosyl) AME (139)
Glycosylation and
Esterification
Suspension cell cultures of
Nicotiana tabacum
[66]
3-O-(6-O-Malonyl-β-d-
glucopyranosyl) AME (140)
Glycosylation and
Esterification
Suspension cell cultures of
Nicotiana tabacum
[66]
Botrydial (54) Botryenedial (141) Dehydration Botrytis cinerea (fungus) [56]
Citrinin (57) Decarboxycitrinin (142) Decarboxylation Moraxella sp. MB1
(bacterium)
[111]
Deoxynivalenol
(DON, 38)
3-epi-Deoxynivalenol (143) Epimerization Nocardioides sp. WSN05-2
(bacterium)
[113]
Devosia sp. (bacterium) [114]
DON-8,15-hemiketal-8-GlcA
(144)
Oxidation and
glucuronidation
Rat liver microsomes (RLM)
[71]
Iso-DON (86) Isomerization RLM [71]
Iso-DON-3-GlcA (92) and
iso-DON-8-GlcA (93)
Isomerization and
glucuronization
RLM [71]
Deepoxy-deoxynivalenol
(DOM, 45)
Iso-DOM (87) Isomerization RLM [71]
Iso-DOM-3-GlcA (95) and
iso-DOM-8-GlcA (96)
Isomerization and
glucuronization
RLM [71]
Fomannoxin (40) Fomannoxin acid (59) and
fomannoxin acid β-glucoside
(145)
Oxidation and
glycosylation
Cell cultures of Pinus
sylvestris
[44]
Toxins 2020,12, 121 20 of 37
Table 13. Cont.
Substrate Product Type Biotransformation System Ref.
Fumonisin B1(115) Hydrolyzed fumonisin B1=
Aminopentol 1 (AP1,
116
) and
2-keto AP1 (132)
Hydolysis and
deamination
Recombinant enzymes from
the bacterium Sphingopyxis
sp.
[87]
Ochratoxin A (OTA,
21)
(4R)-4-Hydroxyochratoxin A
methyl ester (146)
Hydroxylation and
esterification
Cell cultures of wheat and
maize
[31]
(4S)-4-Hydroxyochratoxin A
methyl ester (147)
Hydroxylation and
esterification
Cell cultures of wheat and
maize
[31]
(4R)-4-Hydroxyochratoxin A
4-Oβ-