Trichothecene

Trichothecenes constitute a large group of chemically related mycotoxins. They are produced by fungi of the genera Fusarium, Myrothecium, Trichoderma, Podostroma, Trichothecium, Cephalosporium, Verticimonosporium [ceb; nl; sv] 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. A poisonous mushroom native to Japan and China, Trichoderma cornu-damae (syn. Podostroma cornu-damae), contains six trichothecenes, including satratoxin H, roridin E, and verrucarin A.

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.

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.

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.

The toxicity of trichothecenes is primarily due to their action as protein synthesis inhibitors; this inhibition occurs at ribosomes during all three stages of protein synthesis: initiation, elongation, and termination. During initiation, trichothecenes can either inhibit the association of the two ribosomal subunits or inhibit the function of the mature ribosome by preventing the association of the first tRNA with the start codon. Inhibition at elongation most likely occurs due to trichothecenes preventing the function of peptidyl transferase, the enzyme which catalyzes the formation of new peptide bonds on the 60s ribosomal subunit. Inhibition during termination can also be the result of peptidyl transferase inhibition or the ability of trichothecenes to prevent the hydrolysis required at this final step.