Recent Advances on Macrocyclic Trichothecenes, Their Bioactivities and Biosynthetic Pathway

Abstract

Macrocyclic trichothecenes are an important group of trichothecenes bearing a large ring. Despite the fact that many of trichothecenes are of concern in agriculture, food contamination, health care and building protection, the macrocyclic ones are becoming the research hotspot because of their diversity in structure and biologic activity. Several researchers have declared that macrocyclic trichothecenes have great potential to be developed as antitumor agents, due to the plenty of their compounds and bioactivities. In this review we summarize the newly discovered macrocyclic trichothecenes and their bioactivities over the last decade, as well as identifications of genes tri17 and tri18 involved in the trichothecene biosynthesis and putative biosynthetic pathway. According to the search results in database and phylogenetic trees generated in the review, the species of the genera Podostroma and Monosporascus would probably be great sources for producing macrocyclic trichothecenes. Moreover, we propose that the macrocyclic trichothecene roridin E could be formed via acylation or esterification of the long side chain linked with C-4 to the hydroxyl group at C-15, and vice versa. More assays and evidences are needed to support this hypothesis, which would promote the verification of the proposed pathway.

Characterisation of two unique sesquiterpenoids from Trichoderma hypoxylon

“…Trichothecenes could be divided into two main categories: the simple trichothecenes and the macrocyclic trichothecenes (Type D trichothecenes), while macrocyclic trichothecenes had more potential as antitumor agents compared with the simple trichothecenes (de Carvalho et al 2016;Proctor et al 2018;Smitka et al 1984). Harzianum B was an important precursor of macrocyclic trichothecenes, for which biosynthesis was not integrally elucidated, especially the connection method of macrocycle (Proctor et al 2020;Zhu et al 2020). In this work, two new sesquiterpenes 1-2, together with three known compounds, were isolated and identified.…”

Trichothecenes in Food and Feed, Relevance to Human and Animal Health and Methods of Detection: A Systematic Review

“…TCT is hazardously intoxicating due to their additional potential to be topically absorbed, and their metabolites affect the gastrointestinal tract, skin, kidney, liver, and immune and hematopoietic progenitor cellular systems. Sensitivity to this type of toxin varying from dairy cattle to pigs, with the most sensitive endpoints being neural, immunological, hematological, and reproductive effects [ 17 ]. The mechanism of action mainly consists of the inhibition of protein synthesis and oxidative damage to cells followed by the disruption of nucleic acid synthesis and ensuing apoptosis.…”

“…It is mainly metabolized and eliminated after ingestion, yielding more than 20 metabolites with the hydroxy trichothecenes-2 toxin being the major metabolite [ 16 ]. This family of compounds is divided into four groups according to their structure, named types A, B, C, and D [ 16 , 17 , 18 , 19 , 20 , 21 ]. Trichothecenes are groups of chemically related toxins formed by some filamentous fungal species such as Fusarium , Myrothecium , and Stachybotrys .…”

Fungal Guttation, a Source of Bioactive Compounds, and Its Ecological Role—A Review

“…These trichothecenes were observed to be secreted into the environment via guttation by some Stachybotrys chartarum strains [ 5 ]. However, not all of the macrocyclic trichothecenes are harmful to the human organism; they possess additional activities, e.g., antifungal and anticancer [ 90 , 91 ]. On the other hand, mycotoxins can be found among the peptaibols family.…”