Fungal Ribotoxins: A Review of Potential Biotechnological Applications

Abstract

Fungi establish a complex network of biological interactions with other organisms in nature. In many cases, these involve the production of toxins for survival or colonization purposes. Among these toxins, ribotoxins stand out as promising candidates for their use in biotechnological applications. They constitute a group of highly specific extracellular ribonucleases that target a universally conserved sequence of RNA in the ribosome, the sarcin-ricin loop. The detailed molecular study of this family of toxic proteins over the past decades has highlighted their potential in applied research. Remarkable examples would be the recent studies in the field of cancer research with promising results involving ribotoxin-based immunotoxins. On the other hand, some ribotoxin-producer fungi have already been studied in the control of insect pests. The recent role of ribotoxins as insecticides could allow their employment in formulas and even as baculovirus-based biopesticides. Moreover, considering the important role of their target in the ribosome, they can be used as tools to study how ribosome biogenesis is regulated and, eventually, may contribute to a better understanding of some ribosomopathies.

Characterisation of an antimicrobial and phytotoxic ribonuclease secreted by the fungal wheat pathogenZymoseptoria tritici

“…Additionally, the ∆7-22 mutant is less efficient at interacting with cell membranes thus impairing uptake by endocytosis (Garcia-Ortega et al, 2002). It is speculated that other surface-exposed loops are important for full ribotoxin activity, either through interaction with lipid vesicles or the ribosome itself (Olombrada et al, 2017). Given the similarity between Zt6 and α-sarcin in terms of requirement for a short N-terminal region for full potency, these other regions may also function in the ability of Zt6 to both gain access to cells and to exert ribonucleolytic activity.…”

“…They specifically attack the sarcin-ricin loop (SRL) of the larger eukaryotic rRNA, irreversible blocking protein synthesis and ultimately leading to cell death. For the fungal ribotoxins, much progress has been made at elucidating the modifications that confer these proteins potent toxicity in comparison to non-toxic RNases (Olombrada et al, 2017). In plant-pathogen interactions, it has recently been demonstrated that several RNase-like effectors are secreted by the barley powdery mildew fungus Blumeria graminis f. sp.…”

Characterization of an antimicrobial and phytotoxic ribonuclease secreted by the fungal wheat pathogen Zymoseptoria tritici

“…In addition, the Δ7-22 mutant is less efficient at interacting with cell membranes, thus impairing uptake by endocytosis (Garcia-Ortega et al, 2002). It is speculated that other surface-exposed loops are important for full ribotoxin activity, either through interaction with lipid vesicles or the ribosome itself (Olombrada et al, 2017). Given the similarity between Zt6 and a-sarcin in terms of the requirement for a short N-terminal region for full potency, these other regions may also function in the ability of Zt6 to both gain access to cells and to exert ribonucleolytic activity.…”

“…They specifically attack the sarcin-ricin loop (SRL) of the larger eukaryotic ribosomal RNA (rRNA), irreversibly blocking protein synthesis and ultimately leading to cell death. For the fungal ribotoxins, much progress has been made to elucidate the modifications that confer potent toxicity to these proteins in comparison with non-toxic RNases (Olombrada et al, 2017). In plant-pathogen interactions, it has been demonstrated recently that several RNase-like effectors are secreted by the barley powdery mildew fungus Blumeria graminis f. sp.…”

Ribonuclease as Anticancer Therapeutics

“…By engineering process and chemical modification in ligand/receptor an increase in the cytotoxic properties of RNase molecules may be achieved to selectively allow the cytotoxic pathway to work in the malignant cells. The greater insight in the working mechanisms involved in the efficient uptake and subsequent cytotoxicity of α-sarcin and RIPs in the tumor/ malignant cells have suggested a potent role to these microbial RNases in the anticancer therapy [76]. There is a strong belief that further development in RNase studies will be the prerequisite for development of effective drug(s) against malignant cells and workable anticancer therapeutics.…”