Mini-review Fungal ribotoxins: Natural protein-based weapons against insects Q5 Miriam Olombrada a , Álvaro Martínez-del-Pozo a , Pilar Medina b , Flor Budia b , José G. Gavilanes a , Lucía García-Ortega a, * a Departamento de Bioquímica y Biología Molecular I, Facultad de Química, Universidad Complutense, Avda. Complutense, 28040 Madrid, Spain b Unidad de Protección de Cultivos, E.T.S.I. Agrónomos, Universidad Politécnica de Madrid, 28040 Madrid, Spain article info Article history: Received 7 February 2014 Accepted 25 February 2014 Available online xxxx Keywords: Ribotoxins a-Sarcin Hirsutellin A Entomopathogen Insecticide abstract Ribotoxins are fungal extracellular ribonucleases highly toxic due to their ability to enter host cells and their effective ribonucleolytic activity against the ribosome. The natural role of these proteins in the producing fungi is still unsolved. Nevertheless, recent studies showing the insecticidal properties of two ribotoxins from different origin support their involvement in defense mechanisms. Thus, it seems that not just the entomopathogen Hirsutella thompsonii expresses the ribotoxin hirsutellin A as a virulence factor but also Aspergillus, the main ribotoxin producer, does so. In this review we focus on this little known aspect of this family of proteins, their toxicity against insects, from the point of view of its biological relevance and its potential biotechnological applications. Ó 2014 Published by Elsevier Ltd. Nature provides numerous examples of self defense against predators in all living organisms. In particular, plants, fungi and bacteria produce a high variety of toxins against insects, many of which are proteins. From a biotechnological point of view, some of them are being developed for pest control, since conventional agrochem- ical pesticides show adverse effects on the environment and human health as well as a rapid emergence of pest resistance. Moreover, the high cost of discovering, devel- oping and registering new synthetic pesticides have also contributed to increased interest in biopesticides (Glare et al., 2012). Insect pathogenic fungi are of special interest since they play an important natural role in controlling insect pests. The approximately 1000 known species of entomopatho- genic fungi target most, if not all, insect species, from sucking insects to many coleopteran and orthopteran pests, although individually have narrow host ranges. In fact, products based on the species Beauveria, Metarhizium, Lecanicillium and Isaria are being commercialized (Faria and Wraight, 2007; Kim et al., 2014 Q1 ). However, efficacy limitations like dose response and specificity still need to be overcome. Therefore, a better understanding of fungal pathogenesis in insects at a molecular level is a demanding field in order to improve their application in a natural environment. 1. Hirsutella thompsonii H. thompsonii is a well known entomopathogen fungus registered in 1981 as Mycar for the control of the citrus rust mite (McCoy, 1981). This formulation was soon abandoned due to its poor efficacy in field trials. Nevertheless, this mold has been recently studied against several mites. Mycohit is a formulation registered and commercialized in India for coconut eriophyid mites with success in extensive field trials studies (Sreerama Kumar and Singh, 2008). In fact, Hirsutella shows a high specificity to subclass Acari and it is clearly more virulent than the extensively studied * Corresponding author. E-mail address: lucia@bbm1.ucm.es (L. García-Ortega). Contents lists available at ScienceDirect Toxicon journal homepage: www.elsevier.com/locate/toxicon 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 http://dx.doi.org/10.1016/j.toxicon.2014.02.022 0041-0101/Ó 2014 Published by Elsevier Ltd. Toxicon xxx (2014) 1–6 TOXCON4797_proof ■ 17 March 2014 ■ 1/6 Please cite this article in press as: Olombrada, M., et al., Fungal ribotoxins: Natural protein-based weapons against insects, Toxicon (2014), http://dx.doi.org/10.1016/j.toxicon.2014.02.022