Trichothecenes types

F. equiseti equisetin, fusaro-chromanone, trichothecenes type A B, zearalenone, chrysogine rRNA gene, ITS region PCR 389... 

Trichothecene levels in different matrices vary from pg/kg up to mg/kg depending on a toxin, matrix, climatic condition, as well as other factors. Since toxins can never be completely removed from the food supply, and since they are potential health risks for humans and animals, the European Union has implemented regulations for some of them. The co-occurrence of different trichothecenes (type-A and type-B) in one same foodstuff, could provoke additive or even synergistic effects on human or animal health however, the knowledge regarding this aspects is still scarce. In order to be able to monitor several toxins. 

Recognised may be two additional trichothecene types. The type E trichothecenes include mycotoxins with an opened macrocyclic ring and the type F trichothecenes do not have the 12,13 epoxide ring as it is replaced by a vinyl linkage with the oxygen atom in the epoxide ring removed. 

The resistance of cereals is classified into different groups type I is resistance to primary infection, type II resistance to the spread of infection, type III is the resistance to infection of grains, type IV is tolerance against Fusarium head bhght (FHB) and trichothecenes, type V is the resistance to the accumulation of trichothecenes Class 1 is chemical modification (such as conjugation). Class 2 is inhibition of biosynthesis. 

Of four basic trichothecene groups (A, B, C and D), types A and B represent the most important mycotoxins. Type A includes the T-2 toxin that can suppress the immune system and can cause damage to bone marrow. The T-2 toxin is about 14 times more toxic than the most widespread Fusarium-based type B mycotoxin, deoxynivalenol (DON), previously called vomitoxin. DON is a... 

Ex vivo studies have revealed that trichothecenes can both inhibit and stimulate leukocyte function.12 For example, trichothecenes are toxic to alveolar macrophages,13 but drive differentiation of human myeloid leukemic cells.14 Dose-dependent decreases or increases in B- and T-cell mitogen responses are observable in lymphocytes from animals exposed to T-2 toxin, DON, or various macrocyclic trichothecenes these toxins similarly impair or enhance mitogen-induced lymphocyte proliferation in vitro.12 Rank order of inhibitor potency in rodent and human lymphocyte proliferation assays is Type D > Type A group > Type B group and is dependent on degree of acylation as well as of uptake and metabolism. 

Contamination occurs primarily in wheat, barley, rye, and maize. Type A trichothecenes include mainly T-2 toxin, HT-2, and diacetoxyscirpenol (DAS) mycotoxins of the group B include mainly 4-deoxynivalenol (DON), commonly known as vomitoxin, and nivalenol (NIV). Toxic effects include nausea, vomiting, visual disorder, vertigo, throat irritation, and feed refusal in farm animals. The most toxic is T-2, followed by DAS and NIV, with DON being the least toxic in acute toxicity studies but the most widespread in grains worldwide and therefore the most studied. Issues related to chemical and physical data, occurrence, toxicity, absorption, distribution, and metabolism of trichothecenes are reviewed in WHO (89) and IARC (34). Physicochemical data for some selected Fusarium toxins is given by Sydenham et al. (90). The molecular structures of the main trichothecenes are shown in Fig. 9. 

A number of emerging methods such as fluorescence polarization immunoassays, dipsticks, or even newer methods such as biosensors have been used for rapid screening of mycotoxin (ochratoxin A and Fusarium toxins—funionisms (FBs), moniliformin (MON), zearalenone (ZON), and type-A and -B trichothecenes in foods, fodders, blood, urea, and tissues of pigs after slaughter) (Curtui et al. 2001 Krska et al., 2007). 

U. Berger, M. Oehme and F. Kuhn, Quantitative determination and structure elucidation of type A-and B-trichothecenes by HPLC/ion trap multiple mass spectrometry, 7. Agric. Fd. Chem., 47, 4240-4245 (1999). 

Figure 28 Structures of Fusarium trichothecenes (including trichothecene intermediates isolated as natural products). The side chains (e.g., hydroxyl, acetyl, keto) are added to the trichothecene skeleton at C-3 (FT), C-4 (R2), C-15 (R3), C-7 (R4), and C-8 (R5), which are shaded in colors. While type A trichothecene has a single bond at C-8, type B trichothecene has a keto at C-8. Three rings that constitute the trichothecene skeleton [EPT R1 = (1), R2 = (1), R3 = (1), R4 = (1), R5 = (1)] are labeled A, B, and C in bold. It should be noted that EPT is not a Fusarium trichothecene.

Trichothecene 3-O-acetyltransferase encoded by a noncluster gene, TrilOl, readily converts isotrichodermol (130) into isotrichodermin (ITD, 131) (Figure 30).262 263 This acetylation step is important for the selfprotection of trichothecene-producing Fusarium species. The C-3 acetyl is also essential for subsequent biosynthetic steps to proceed. Indeed, the 7W/0/--targeted gene disruption mutant of F. sporotrichioides could not metabolize 3-hydroxytrichothecenes, but efficiently converted exogenously added ITD (131) and other C-3 acetylated intermediates into T-2 toxin.264 After ITD (131), the biosynthetic pathways are different between type A and type B trichothecenes. 

H) Type B trichothecenes In the biosynthesis of type B trichothecenes, three biosynthetic routes to the next oxygenation step operate after ITD (131) (see Figure 32). This pathway diversification is attributed to the function of a key hydroxylase encoded by FgTril,273 which is similar to but distinct from its homologue FsTril. FgTRIl enzyme is a multifunctional CYP that oxygenates both C-7 and C-8 of ITD (131) and CAL... 

Figure 31 Biosynthesis of type A trichothecenes. ITD (131) is metabolized to T-2 toxin along the biosynthetic grids. Either C-8 hydroxylation or C-4 hydroxylation of CAL (133) may occur.

For the biosynthesis of a model type A trichothecene T-2 toxin, all the necessary Tri genes were already identified.226 However, there still remain two Tri genes as-yet-unidentified for the biosynthesis of 4-ANIV, a model type B trichothecene. These include genes encoding DHC C-8 oxidoreductase, whose activity was also detected from F. verticittioides (teleomorph genus Gibberella), which does not produce trichothecenes,274 and trichothecene C-15 deacetylase,292 whose distribution and substrate specificity are not well examined. 

Several species of Fusarium infect com, wheat, barley, and rice. Under favorable conditions they elaborate a number of different types of tetracyclic sesquiterpenoid mycotoxins that are composed of the epoxytrichothecene skeleton and an olefinic bond with different side chain substitutions (fig. 9). Based on the presence of a macrocyclic ester or ester-ether bridge between C-4 and C-15, trichothecenes are generally classified as macrocyclic (type C) or nonmacrocyclic (types A and B) (table 5). Other fungal genera producing trichothecenes are Myrothecium, Trichoderma, Trichothecium, Acremonium, Verticimonosporium and Stachybotrys. The term trichothecenes is derived from trichothecin, the first compound isolated in this group [115, 147-153]. 

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