Department of Biochemistry and Molecular Biology and Physiology, Faculty of Sciences , University of Valladolid , E-47011 Valladolid , Spain.
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies , University of Campania "Luigi Vanvitelli" , I-81100 Caserta , Italy.
ACS Chem Biol. 2019 Jun 21;14(6):1319-1327. doi: 10.1021/acschembio.9b00291. Epub 2019 Jun 10.
Ribotoxins make up a group of extracellular rRNA endoribonucleases produced by ascomycetes that display cytotoxicity toward animal cells, having been proposed as insecticidal agents. Recently, the ribotoxin Ageritin has been isolated from the basidiomycetes Agrocybe aegerita (poplar mushroom), suggesting that ribotoxins are widely distributed among fungi. To gain insights into the protective properties of Ageritin against pathogens and its putative biotechnological applications, we have tested several biological activities of Ageritin, comparing them with those of the well-known ribotoxin α-sarcin, and we found that Ageritin displayed, in addition to the already reported activities, (i) antibacterial activity against Micrococcus lysodeikticus, (ii) activity against the tobacco mosaic virus RNA, (iii) endonuclease activity against a supercoiled plasmid, (iv) nuclease activity against genomic DNA, (v) cytotoxicity to COLO 320, HeLa, and Raji cells by promoting apoptosis, and (vi) antifungal activity against the green mold Penicillium digitatum. Therefore, Ageritin and α-sarcin can induce resistance not only to insects but also to viruses, bacteria, and fungi. The multiple biological activities of Ageritin could be exploited to improve resistance to different pathogens by engineering transgenic plants. Furthermore, the induction of cell death by different mechanisms turns these ribotoxins into useful tools for cancer therapy.
核糖核酸酶构成了一组由子囊菌产生的细胞外 rRNA 内切核糖核酸酶，对动物细胞具有细胞毒性，被提议作为杀虫剂。最近，从担子菌 Agrocybe aegerita（杨树菇）中分离出核糖核酸酶 Ageritin，表明核糖核酸酶在真菌中广泛分布。为了深入了解 Ageritin 对病原体的保护特性及其潜在的生物技术应用，我们测试了 Ageritin 的几种生物学活性，并将其与著名的核糖核酸酶 α-菌毒素进行了比较，我们发现 Ageritin 除了已经报道的活性外，还具有（i）对微球菌 lysodeikticus 的抗菌活性，（ii）对烟草花叶病毒 RNA 的活性，（iii）对超螺旋质粒的内切核酸酶活性，（iv）对基因组 DNA 的核酸酶活性，（v）通过促进细胞凋亡对 COLO 320、HeLa 和 Raji 细胞的细胞毒性，以及（vi）对绿霉 Penicillium digitatum 的抗真菌活性。因此，Ageritin 和 α-菌毒素不仅可以诱导对昆虫的抗性，还可以诱导对病毒、细菌和真菌的抗性。通过工程转基因植物，可以利用 Ageritin 的多种生物学活性来提高对不同病原体的抗性。此外，不同机制诱导的细胞死亡使这些核糖核酸酶成为癌症治疗的有用工具。
