Fumagillin, a Mycotoxin of Aspergillus fumigatus: Biosynthesis, Biological Activities, Detection, and Applications
by
Xabier Guruceaga 1, Uxue Perez-Cuesta 1, Ana Abad-Diaz de Cerio 1
, Oskar Gonzalez 2, Rosa M. Alonso 2, Fernando Luis Hernando 1, Andoni Ramirez-Garcia 1,* and Aitor Rementeria 1,*
Xabier Guruceaga 1, Uxue Perez-Cuesta 1, Ana Abad-Diaz de Cerio 1, Oskar Gonzalez 2, Rosa M. Alonso 2, Fernando Luis Hernando 1, Andoni Ramirez-Garcia 1,* and Aitor Rementeria 1,*
1
Fungal and Bacterial Biomics Research Group, Department of Immunology, Microbiology and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, 48940 Leioa, Spain
2
FARMARTEM Group, Department of Analytical Chemistry, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, 48940 Leioa, Spain
*
Authors to whom correspondence should be addressed.
Toxins 2020, 12(1), 7; https://doi.org/10.3390/toxins12010007
Received: 27 November 2019 / Revised: 17 December 2019 / Accepted: 18 December 2019 / Published: 20 December 2019
(This article belongs to the Special Issue Mycotoxin Biosynthesis and Genetic Transformation Systems in Fungi)
Fumagillin is a mycotoxin produced, above all, by the saprophytic filamentous fungus Aspergillus fumigatus. This mold is an opportunistic pathogen that can cause invasive aspergillosis, a disease that has high mortality rates linked to it. Its ability to adapt to environmental stresses through the production of secondary metabolites, including several mycotoxins (gliotoxin, fumagillin, pseurotin A, etc.) also seem to play an important role in causing these infections. Since the discovery of the A. fumigatus fumagillin in 1949, many studies have focused on this toxin and in this review we gather all the information currently available. First of all, the structural characteristics of this mycotoxin and the different methods developed for its determination are given in detail. Then, the biosynthetic gene cluster and the metabolic pathway involved in its production and regulation are explained. The activity of fumagillin on its target, the methionine aminopeptidase type 2 (MetAP2) enzyme, and the effects of blocking this enzyme in the host are also described. Finally, the applications that this toxin and its derivatives have in different fields, such as the treatment of cancer and its microsporicidal activity in the treatment of honeybee hive infections with Nosema spp., are reviewed. Therefore, this work offers a complete review of all the information currently related to the fumagillin mycotoxin secreted by A. fumigatus, important because of its role in the fungal infection process but also because it has many other applications, notably in beekeeping, the treatment of infectious diseases, and in oncology.
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Keywords:
fumagillin; Aspergillus fumigatus; chemical detection; metabolic pathway and regulation; MetAP2 enzyme; cancer treatment; microsporicidal activity; honeybee hive infections
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MDPI and ACS Style
Guruceaga, X.; Perez-Cuesta, U.; Abad-Diaz de Cerio, A.; Gonzalez, O.; Alonso, R.M.; Hernando, F.L.; Ramirez-Garcia, A.; Rementeria, A. Fumagillin, a Mycotoxin of Aspergillus fumigatus: Biosynthesis, Biological Activities, Detection, and Applications. Toxins 2020, 12, 7.
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