Trichothecenes constitute a large group of chemically related mycotoxins. They are produced by fungi of the genera Fusarium, Myrothecium, Trichoderma, Trichothecium, Cephalosporium, Verticimonosporium and Stachybotrys. Chemically, trichothecenes are a class of sesquiterpenes. All trichothecenes share a cyclic terpene core but differ in the type of functional groups (R groups) attached to the carbon backbone. They are produced on many different grains such as wheat, oats, or maize by various Fusarium species including F. graminearum, F. sporotrichioides, F. poae, and F. equiseti. Some moulds that produce trichothecene mycotoxins, such as Stachybotrys chartarum, can grow in damp indoor environments. It has been found that macrocyclic trichothecenes produced by S. chartarum can become airborne and thus contribute to health problems in humans. Trichoderma cornu-damae (syn. Podostroma cornu-damae), a mushroom native to Asia, contains potentially fatal levels of satratoxin H.
Classification
General classification
Trichothecenes are a group of over 150 chemically related toxic mycotoxins. Each trichothecene displays a core structure consisting of a six-membered ring containing a single oxygen atom, flanked by two carbon rings. This core ring structure contains an epoxide bridging carbons 12 and 13, as well as a double bond between carbons 9 and 10. These two functional groups are primarily responsible for trichothecenes' ability to inhibit protein synthesis and incur general cytotoxic effects. Notably, this core structure is amphipathic, containing both polar and nonpolar parts. All trichothecenes are related through this common structure but are differentiated by the substitution pattern of oxygen-containing functional groups on carbons 3, 4, 7, 8, and 15. These functional groups govern the properties of an individual trichothecene and also serve as the basis for the most commonly used classification system for this family of toxins. This classification system breaks up the trichothecene family into four groups: Type A, B, C, and D.
Type A trichothecenes have hydroxyl or O-linked ester substitutions around the core ring structure. Common examples of these are neosolaniol with a hydroxyl substitution at carbon 8, and T-2 toxin with an ester substitution at carbon 8. Type B trichothecenes are classified by the presence of oxo-substitutions around the core ring structure. Common examples of these include nivalenol and trichothecene, which both have a ketone functional group at carbon 8. Type C trichothecenes have an additional epoxide bridging the carbons 7 and 8. A common example of this is crotocin, which also has an O-linked ester functional group at carbon 4. Type D trichothecenes have an additional macrocylic ring between carbon 4 and carbon 15. These rings can have varied additional functional groups. Common examples of these are roridin A and satratoxin H. Although the distinct functional groups of these classification types give each trichothecene unique chemical properties, their classification type does not explicitly indicate their relative toxicity. While the type D group is thought to contain the most toxic trichothecenes, type A and B trichothecenes vary considerably in their toxicity.
Alternative classifications The classification system described above is the most commonly used to group molecules of the trichothecene family. However, a variety of alternative classification systems also exist for these complex molecules. Trichothecenes can also be generally described as simple or macrocyclic. Simple trichothecenes include types A, B, and C, whereas macrocyclic trichothecenes include Type D and are characterized by the presence of a carbon 4 – carbon 15 bridge. Additionally, J. F. Grove proposed a classification of trichothecenes into three groups that was also based upon the functional substitution patterns of the ring skeleton. Group 1 trichothecenes only have functional groups substituted on the third, fully saturated carbon ring. Group 2 trichothecenes contain additional functional groups on the core ring containing the 9, 10 carbon double bond. Finally, group 3 trichothecenes contain a ketone functional group at carbon 8; this is the same criteria for type B trichothecenes. Advances in the field of evolutionary genetics have also led to the proposal of trichothecene classification systems based on the pathway of their biosynthesis. Genes responsible for the biosynthesis of a mycotoxin are typically located in clusters; in Fusariumi these are known as TRI genes. TRI genes are each responsible for producing an enzyme that carries out a specific step in the biosynthesis of trichothecenes. Mutations in these genes can lead to the production of variant trichothecenes and therefore these molecules could be grouped based on shared biosynthesis steps. For example, a shared step in the biosynthesis of trichothecenes is controlled by the gene TRI4. This enzyme product controls the addition of either three or four oxygen atoms to trichodiene to form either isotrichodiol or isotrichotriol respectively. A variety of trichothecenes can then be synthesized from either of these intermediates and they could therefore be classified as either t-type if synthesized from isotrichotriol or d-type if synthesized from isotrichodiol.
Mechanism of action
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