Abstract

Fungi are a rich source of natural products with biological activities. In this study, we evaluated viral effects on secondary metabolism of the rice blast fungus Magnaporthe oryzae using an isolate of APU10-199A co-infected with three types of mycoviruses: a totivirus, a chrysovirus, and a partitivirus. Comparison of the secondary metabolite profile of APU10-199A with that of the strain lacking the totivirus and chrysovirus showed that a mycotoxin tenuazonic (TeA) acid was produced in a manner dependent on the mycoviruses. Virus reinfection experiments verified that TeA production was dependent on the totivirus. Quantitative reverse transcription PCR and RNA-sequencing analysis indicated the regulatory mechanism underlying viral induction of TeA: the totivirus activates the TeA synthetase gene TAS1 by upregulating the transcription of the gene encoding a Zn(II)2-Cys6-type transcription factor, TAS2. To our knowledge, this is the first report that confirmed mycovirus-associated regulation of secondary metabolism at a transcriptional level by viral reinfection. Because only treatment with dimethyl sulfoxide has been reported to trigger TeA production in this fungus without gene manipulation, our finding highlights the potential of mycoviruses as an epigenomic regulator of fungal secondary metabolism.

Highlights

  • Fungi produce structurally diverse secondary metabolites (SMs), and are a rich source of compounds for drug discovery

  • M. oryzae strains were grown on potato dextrose agar (PDA; BD, Franklin Lakes, NJ, United States), and agar plugs were inoculated into liquid media

  • Because fungal secondary metabolism is influenced by nutrient regimes and physical parameters (Bode et al, 2002), we cultured M. oryzae in three different media: SS, potato dextrose broth (PDB), and IPN with agitation at two different rates (40 and 150 rpm)

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Summary

Introduction

Fungi produce structurally diverse secondary metabolites (SMs), and are a rich source of compounds for drug discovery. Since discovery of the first antibiotic penicillin, thousands of bioactive compounds, such as cyclosporine and lovastatin, have been found in fungi and reported (Bérdy, 2005). Some fungi can produce mycotoxins, which are a great threat to human health. Aflatoxins, carcinogenic mycotoxins produced by certain Aspergillus species, cause poisoning of grains (Bennett and Klich, 2003). A human fungal pathogen, Aspergillus fumigatus, produces a mycotoxin gliotoxin, which is implicated in the virulence of the fungus (Sugui et al, 2007). Studies of fungal genomes have revealed that fungi have the potential to produce more SMs than expected, as they have a large number of genes for secondary metabolism

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