1. Academic Validation
  2. Fungal Melanin Biosynthesis Pathway as Source for Fungal Toxins

Fungal Melanin Biosynthesis Pathway as Source for Fungal Toxins

  • mBio. 2022 Jun 28;13(3):e0021922. doi: 10.1128/mbio.00219-22.
Jia Gao 1 Max Wenderoth 1 Maria Doppler 2 3 Rainer Schuhmacher 2 Doris Marko 4 Reinhard Fischer 1
Affiliations

Affiliations

  • 1 Karlsruhe Institute of Technologygrid.7892.4 (KIT), Institute for Applied Biosciences, Department of Microbiology, Karlsruhe, Germany.
  • 2 University of Natural Resources and Life Sciencesgrid.5173.0, Vienna, Department of Agrobiotechnology (IFA-Tulln), Institute of Bioanalytics and Agro-Metabolomics, Tulln, Austria.
  • 3 University of Natural Resources and Life Sciencesgrid.5173.0, Vienna, Core Facility Bioactive Molecules: Screening and Analysis, Tulln, Austria.
  • 4 University of Vienna, Department of Food Chemistry and Toxicology, Vienna, Austria.
Abstract

Contamination of food and feed with toxin-producing fungi is a major threat in agriculture and for human health. The filamentous fungus Alternaria alternata is one of the most widespread postharvest contaminants and a weak plant pathogen. It produces a large variety of secondary metabolites with alternariol and its derivatives as characteristic mycotoxin. Other important phyto- and mycotoxins are perylene Quinones (PQs), some of which have Anticancer properties. Here, we discovered that the PQ altertoxin (ATX) biosynthesis shares most enzymes with the 1,8-dihydroxynaphthalene (1,8-DHN) melanin pathway. However, melanin was formed in aerial hyphae and spores, and ATXs were synthesized in substrate hyphae. This spatial separation is achieved through the promiscuity of a polyketide synthase, presumably producing a pentaketide (T4HN), a hexaketide (AT4HN), and a heptaketide (YWA1) as products. T4HN directly enters the altertoxin and DHN melanin pathway, whereas AT4HN and YWA1 can be converted only in aerial hyphae, which probably leads to a higher T4HN concentration, favoring 1,8-DHN melanin formation. Whereas the production of ATXs was strictly dependent on the CmrA transcription factor, melanin could still be produced in the absence of CmrA to some extent. This suggests that different cues regulate melanin and toxin formation. Since DHN melanin is produced by many fungi, PQs or related compounds may be produced in many more fungi than so far assumed. IMPORTANCE Mycotoxins are a major threat for human health. Food safety control relies on the identification of the toxins or the detection of the expression of the respective genes. The latter method, however, relies on the knowledge of the biosynthetic pathway and the key genes. Alternaria alternata is a major food contaminant and produces many different mycotoxins with altertoxins and other perylene Quinones as prominent examples. Here, we discovered that the biosynthetic pathway for altertoxins shares most of the enzymes with the dihydroxynaphthalene (DHN) melanin pathway. Because the DHN melanin pathway is widespread among fungi, the production of mycotoxins of the perylene quinone class could be more widespread than so far anticipated.

Keywords

Alternaria; Alternaria alternata; altertoxin; food safety; melanin; mycotoxin; perylene quinone; secondary metabolite.

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