Abstract
Ageritin is a specific ribonuclease, extracted from the edible mushroom Cyclocybe aegerita (synonym Agrocybe aegerita), which cleaves a single phosphodiester bond located within the universally conserved alpha-sarcin loop (SRL) of 23–28S rRNAs. This cleavage leads to the inhibition of protein biosynthesis, followed by cellular death through apoptosis. The structural and enzymatic properties show that Ageritin is the prototype of a novel specific ribonucleases family named ‘ribotoxin-like proteins’, recently found in fruiting bodies of other edible basidiomycetes mushrooms (e.g., Ostreatin from Pleurotus ostreatus, Edulitins from Boletus edulis, and Gambositin from Calocybe gambosa). Although the putative role of this toxin, present in high amount in fruiting body (>2.5 mg per 100 g) of C. aegerita, is unknown, its antifungal and insecticidal actions strongly support a role in defense mechanisms. Thus, in this review, we focus on structural, biological, antipathogenic, and enzymatic characteristics of this ribotoxin-like protein. We also highlight its biological relevance and potential biotechnological applications in agriculture as a bio-pesticide and in biomedicine as a therapeutic and diagnostic agent.
Highlights
Since always, nature inspires medicine for the diversity of biologically active compounds with therapeutic properties and the great attention that researchers paid on mushrooms is one of the most appropriate examples, which deserves to be further investigated.Many fungal species are traditionally used in Chinese medicine or as functional foods in Japan and other Asian countries, representing a great source of nutraceuticals, functional foods, and secondary metabolites
They are produced by fungi belonging to Ascomycota phylum, mostly from the genus Aspergillus, such as the prototype α-sarcin from Aspergillus giganteus [4] and restrictocin and mitogillin from Aspergillus restrictus [5], while hirsutellin A and anisoplin are isolated by Hirsutella thompsonii and Metarhizium anisopliae, respectively [6,7]
A novel family of protein synthesis inhibitors has been discovered in fungi belonging to Basidiomycota phylum. These enzymes, the prototype of which is Ageritin from Cyclocybe aegerita, are specific ribonucleases, named as ribotoxin-like proteins (RL-Ps), that, as ascomycetes ribotoxins, basically act on large ribosomal RNA (rRNA), releasing the specific α-fragment, the two families differ in structure and mechanism of action [14,15]
Summary
Nature inspires medicine for the diversity of biologically active compounds with therapeutic properties and the great attention that researchers paid on mushrooms is one of the most appropriate examples, which deserves to be further investigated. Many fungal species are traditionally used in Chinese medicine or as functional foods in Japan and other Asian countries, representing a great source of nutraceuticals, functional foods, and secondary metabolites In this context, fungi are useful to discovering new drugs; and many bioactive compounds such as small molecules, polysaccharides, proteins, and polysaccharide–protein complexes have been isolated from them [1,2]. Fungal ribotoxins are a family of highly specific extracellular rRNA endonucleases (EC 3.1.27.10) well studied since 1960 They are produced by fungi belonging to Ascomycota phylum, mostly from the genus Aspergillus, such as the prototype α-sarcin from Aspergillus giganteus [4] and restrictocin and mitogillin from Aspergillus restrictus [5], while hirsutellin A and anisoplin are isolated by Hirsutella thompsonii and Metarhizium anisopliae, respectively [6,7]. These enzymes, the prototype of which is Ageritin from Cyclocybe aegerita (synonym Agrocybe aegerita), are specific ribonucleases, named as ribotoxin-like proteins (RL-Ps), that, as ascomycetes ribotoxins, basically act on large rRNA, releasing the specific α-fragment, the two families differ in structure and mechanism of action (see Sections 5 and 6) [14,15]
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