**4.** *Fusarium* **toxins**

Mycotoxins are toxic secondary metabolites produced by fungi and are capable of causing diseases in both animals and humans. Mycotoxins may produce birth defects, abortion, tremors, and cancers [27–30]. Among the major mycotoxin-producing fungi are *Aspergillus*, *Claviceps*, *Fusarium*, and *Penicillium* species [27, 28]. *Fusarium* fungi are the most widespread in cereal-growing areas of the world and produce a diversity of mycotoxin types. The most prevalent *Fusarium* toxins are zearalenone, fumonisin, moniliformin, and trichothecenes (T-2/ HT-2 toxin, deoxynivalenol, diacetoxyscirpenol, nivalenol) [5, 28, 30, 31].

Zearalenone is a group of estrogenic metabolites produced by several species of *Fusarium*, the most known of which is *F. graminearum* [5, 28]. Zearalenone is the generic name for a complex macrocyclic molecule and is derived from the perfect stage of the fungus *F. graminearum* (*Gibberella zeae*) [28]. *Fusarium* infection and zearalenone production are most notable on barley, corn, oat, sorghum, and wheat. *Fusarium* causes crown rot of corn, and scab of barley, oat, and wheat. Zearalenone is produced in infected plants in the field and in stored food and feed stuffs including cereal grains [5, 28].

Zearalenone is frequently implicated in reproductive disorders of farm animals and occasionally in hyperoestrogenic syndromes in humans [28, 32]. It has been reported that zearalenone possess estrogenic activity in cattle, pigs, and sheep. The biotransformation for zearalenone in animals involves the formation of two metabolites α-zearalenol and β-zearalenol, which are subsequently conjugated with glucuronic acid [32]. Moreover, zearalenone has also been shown to be hepatotoxic, hematotoxic, immunotoxic, and genotoxic.

Fumonisins are hydroxylated long-chain alkylamines esterified with propanetricarboxylic acid moieties produced by *Fusarium moniliforme* worldwide [33, 34]. The fumonisins have been reported carcinogenic in laboratory rats. It has also been reported that consumption of corn contaminated with *Fusarium moniliforme* is associated with higher than average incidence of esophageal cancer, and fumonisins may be responsible. Fumonisins are structurally similar to sphingosine and may exert their biological activity through their ability to block key enzymes (sphinganine- and sphingosine-N-acyltransferases) involved in sphingolipid biosynthesis.

Moniliformin is produced by several *Fusarium* species on cereals worldwide [31, 35]. Moniliformin is a small and ionic molecule that forms only a single sensitive fragment ion in the collision cell of a tandem mass spectrometer. There is great variability in the moniliformin synthesized by *Fusarium* spp. [35]. It has been reported that moniliformin in large amounts acts at the level of sugar metabolism and is cytotoxic at high concentrations in mammalian cells [35]. In addition, this toxin causes intoxication, and the lesions include intestinal hemorrhage, muscle weakness, breathing difficulty, cyanosis, coma, and death.

Trichothecenes are a very large group of mycotoxins produced by various species of *Fusarium*, *Cephalosporium*, *Myrothecium*, *Stachybotrys, Trichoderma*, *Trichothecium*, and *Verticimonosporium*. The generic name "trichothecene" has been derived from a *Trichothecium* species from which the first of these related compounds was isolated [28]. Trichothecenes belong to sesquiterpene compounds. They are produced on many different grains, e.g., corn, oats, and wheat by various *Fusarium* species such as *F. graminearum*, *F. poae*, and *F. sporotrichioides* [28, 36, 37].

There are several types of trichothecene mycotoxins, including deoxynivalenol, diacetoxyscirpenol, HT-2 mycotoxins, neosolaniol, nivalenol, satratoxin-H, T-2 mycotoxins, verrucarin A, and vomitoxin. Exposure to trichothecene mycotoxins can cause different symptoms in people such as dry eyes, tiredness, fatigue, vomiting, diarrhea, abdominal pain, mental impairment, rash, and bleeding [28]. In addition, T-2 mycotoxins are also substances for biological warfare that can be absorbed through a person's skin [37].

**4.** *Fusarium* **toxins**

Source: The *Fusarium* Laboratory Manual [3].

Mycotoxins are toxic secondary metabolites produced by fungi and are capable of causing diseases in both animals and humans. Mycotoxins may produce birth defects, abortion, tremors, and cancers [27–30]. Among the major mycotoxin-producing fungi are *Aspergillus*, *Claviceps*, *Fusarium*, and *Penicillium* species [27, 28]. *Fusarium* fungi are the most widespread in cereal-growing areas of the world and produce a diversity of mycotoxin types. The most prevalent *Fusarium* toxins are zearalenone, fumonisin, moniliformin, and trichothecenes (T-2/

Zearalenone is a group of estrogenic metabolites produced by several species of *Fusarium*, the most known of which is *F. graminearum* [5, 28]. Zearalenone is the generic name for a complex macrocyclic molecule and is derived from the perfect stage of the fungus *F. graminearum* (*Gibberella zeae*) [28]. *Fusarium* infection and zearalenone production are most notable on

HT-2 toxin, deoxynivalenol, diacetoxyscirpenol, nivalenol) [5, 28, 30, 31].

*Fusarium* **species Host plants Geographic distribution**

18 Fusarium - Plant Diseases, Pathogen Diversity, Genetic Diversity, Resistance and Molecular Markers

*F. polyphialidicum* Sorghum grain Australia, Italy, South Africa

*F. nygamai* Sorghum Arid regions *F. oxysporum* Many plant species Worldwide *F. phyllophilum Dracaena* and *Sansevieria* species Europe, Japan *F. poae* Cereal Worldwide

*F. proliferatum* Asparagus, corn, mango, sorghum Worldwide *F. pseudoanthophilum* Corn Southern Africa *F. pseudograminearum* Barley, triticale, wheat Drier areas worldwide

*F. pseudonygamai* Pearl millet Africa, US *F. ramigenum Ficus carica* US

*F. succisae Succisa pratensis* Europe

*F. venenatum* Several plant species Europe *F. verticillioides* Corn Worldwide

**Table 1.** Plant pathogen *Fusarium species*, their host, and geographic distribution.

*F. redolens* Many hosts Temperate regions *F. sacchari* Corn, sugarcane Mexico, Philippines *F. semitectum* Banana Subtropical regions *F. solani* Many plant species Worldwide *F. sterilihyphosum* Mango South Africa

*F. subglutinans* Corn Cooler corn-growing areas

*F. thapsinum* Sorghum All sorghum-growing areas

*F. udum* Pigeon pea Southern Asia, sub-Saharan of Africa

*F. torulosum* Several plant species Temperate regions

Trichothecenes are typically found in plants when the autumn is cool and wet that delays harvest of grains such as corn. The toxins are also found in animal feeds that contain contaminated grain with *Fusarium*. Joffe [39] reported that trichothecenes are among the most toxic mycotoxins. He found that the LD50 rate for laboratory mice given trichothecene mycotoxins is between 1 and 7 mg/kg, depending on the specific type of trichothecene and the method of exposure [38, 39]. Toxicity of trichothecene in human is documented since 1913 when people in Russia consumed cereals that overwintered in the field [38, 39].
