The identification of a key gene highlights macrocyclic ring’s role in trichothecene toxicity

Authors: McCormick, Susan; CARDOZA, ROSA - University Of Leon; MARTÍNEZ-REYES, NATALIA - University Of Leon; Vermillion, Karl; Busman, Mark; RODRÍGUEZ-GONZÁLEZ, ALVARO - University Of Leon; CASQUERO, PEDRO - University Of Leon; Proctor, Robert; GUTIÉRREZ, SANTIAGO - University Of Leon

Submitted to: Applied Microbiology and Biotechnology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/28/2024
Publication Date: 9/28/2024
Citation: McCormick, S.P., Cardoza, R.E., Martínez-Reyes, N., Vermillion, K., Busman, M., Rodríguez-González, A., Casquero, P.A., Proctor, R.H., Gutiérrez, S. 2024. The identification of a key gene highlights macrocyclic ring’s role in trichothecene toxicity. Applied Microbiology and Biotechnology. https://doi.org/10.1007/s00253-024-13297-x.
DOI: https://doi.org/10.1007/s00253-024-13297-x

Interpretive Summary: Trichothecenes are among the fungal toxins of most concern to food and feed safety because of their potent toxicity and their frequent occurrence in crops used to produce human food and animal feed. All trichothecenes have the same basic chemical structure, but some also have a large ring structure (macrocyclic ring) that can markedly increase toxicity. Although the genetic and biochemical processes that lead to the formation of the basic trichothecene structure are well understood, there is almost no information on the processes that lead to formation of the macrocyclic ring. Therefore, researchers at ARS in Peoria, Illinois, and the University of Leon, Leon, Spain, used a combination of comparative genome sequence, genetic and chemical analyses to identify a fungal gene that is required for formation of the macrocyclic ring. This research provides critical knowledge on the genetic basis in fungi for production of trichothecenes with the highest levels of toxicity. In addition, the results provide a genetic marker that can be used to distinguish between fungi that produce trichothecenes with a macrocyclic ring from fungi that do not.

Technical Abstract: Trichothecenes are toxins produced by certain species from several fungal genera, including Aspergillus, Fusarium, Isaria, Paramyrothecium, Stachybotrys and Trichoderma. The toxins are of interest because they contribute to the toxigenicity, plant pathogenicity, and/or biological control activities of some fungi. All trichothecenes have the same core 12,13-epoxytrichothec-9-ene (EPT) structure but can differ from one another by the presence or absence of a macrocyclic ring formed from isoprenoid and polyketide substituents esterified to carbon atoms 4 and 15 of EPT, respectively. Genes required for formation and some modifications of EPT have been elucidated, but almost nothing is known about genes specific to formation of the macrocyclic ring. Therefore, we used genomic, transcriptomic, metabolomic, and gene deletion analyses to identify genes that are required specifically for formation of the macrocyclic ring. These analyses identified one gene, TRI24, that is predicted to encode an acyltransferase and that is required for macrocyclic ring formation during biosynthesis of macrocyclic trichothecenes by the fungus Paramyrothecium roridum. In addition, a TRI24 deletion mutant of P. roridum caused less severe disease symptoms on common bean and had less antifungal activity than its wild-type progenitor strain. We propose that the reduced aggressiveness and antifungal activity of the mutant resulted from its inability to produce trichothecenes with a macrocyclic ring. To our knowledge, this is the first report of a gene required specifically for formation of the macrocyclic ring of trichothecenes and that loss of the macrocyclic ring of trichothecenes can alter biological activities of a fungus.