Mycotoxins

Abstract

Mycotoxins are a class of natural fungal metabolites that are specifically toxic to mammals and are frequent contaminants of foods and feeds. In this article we describe mycotoxins from Ascomycota or sac fungi, the largest phylum of fungi, which includes penicillia, aspergilli, fusaria, alternaria, claviceps and other non‐Basidiomycota (‘higher fungi’ or mushroom‐producing) genera. We discuss the toxicity and biosynthesis of the most agriculturally important mycotoxins, namely, polyketide toxins (fumonisins, aflatoxins, ochratoxins, patulin and zearalenone), nonribosomal peptide toxins (ergot alkaloids and tremorgenic toxins) and trichothecenes produced via the terpene biosynthesis pathway. The Ascomycota produce mycotoxins in crops both before harvest and during storage. The genes required for biosynthesis are usually clustered. Transcriptional regulation of biosynthesis involves a pathway‐specific Cys6Zn2 type protein as well as a secondary metabolite‐specific methyltransferase, LaeA. Both of these transcription factors are unique to fungi. Hypotheses about the evolution of mycotoxin biosynthesis in fungi are discussed.

Key Concepts:

  • Mycotoxins are produced by ascomycete (‘lower’) fungi in certain agriculturally important crops.

  • The most common mycotoxins exert a variety of generally nonlethal toxic effects in animals.

  • Biosynthesis of mycotoxins usually involves a co‐regulated, clustered set of genes on one chromosome.

  • Co‐regulation involves transcription factors of the Cys6Zn2 type and a putative methyltransferase, LaeA.

  • Mycotoxins can be of several types: polyketides, nonribosomal peptides or terpene‐derived metabolites.

  • Mycotoxin biosynthesis has evolved in fungi in the absence of agriculture and is not strictly associated with fungal virulence in contaminated crops.

Keywords: mycotoxin; mycotoxicoses; aflatoxin; trichothecene; fumonisin; Aspergillus; Fusarium; Penicillium; biosynthesis; secondary metabolite

Figure 1.

Aflatoxins.

Figure 2.

Fumonisins. Modified from Chu .

Figure 3.

Selected trichothecenes. Modified from Chu .

Figure 4.

Tremorgenic mycotoxins.

Figure 5.

Miscellaneous mycotoxins.

close

References

Bhatnagar D, Rajasekaran K, Cary JW et al. (2008) Molecular approaches to development of resistance to preharvest aflatoxin contamination. In: Leslie JF, Bandyopadhyah R and Visconti A (eds) Mycotoxins: Detection Methods, Management, Public Health, and Agricultural Trade, pp. 257–276. Cambridge, MA: CAB International.

Bok JW, Hoffmeister D, Maggio‐Hall LA et al. (2006) Genomic mining for Aspergillus natural products. Chemical Biology 13: 31–37.

Botha CJ and Naude TW (2002) Plant poisonings and mycotoxicoses of importance in horses in southern Africa. Journal of the South African Veterinary Association‐Tydskrif Van Die Suid‐Afrikaanse Veterinere Vereniging 73: 91–97.

Carbone I, Ramirez‐Prado JH, Jakobek JL et al. (2007) Gene duplication, modularity and adaptation in the evolution of the aflatoxin gene cluster. BMC Evolutionary Biology 7: 111.

Chu FS (1998) Mycotoxins – occurrence and toxic effects. In: Encyclopedia of Food and Nutrition‐Food Contaminants, pp. 858–869. New York: Academic Press.

Cressey PJ (2009) Mycotoxin risk management in New Zealand and Australian food. World Mycotoxin Journal 2: 113–118.

Dorner JW (2009) Biological control of aflatoxin contamination in corn using a nontoxigenic strain of Aspergillus flavus. Journal of Food Protection 72: 801–804.

Du W, Obrian GR and Payne GA (2007) Function and regulation of aflJ in the accumulation of aflatoxin early pathway intermediate in Aspergillus flavus. Food Additives & Contaminants 24: 1043–1050.

Duarte SC, Pena A and Lino CM (2010) A review on ochratoxin A occurrence and effects of processing of cereal and cereal derived food products. Food Microbiology 27: 187–198.

Egner PA, Yu X, Johnson JK et al. (2003) Identification of aflatoxin M1‐N7‐guanine in liver and urine of tree shrews and rats following administration of aflatoxin B1. Chemical Research Toxicology 16: 1174–1180.

Ehrlich KC (2006) Evolution of the aflatoxin gene cluster. Mycotoxin Research 22: 9–15.

Ehrlich KC (2009) Predicted roles of the uncharacterized clustered genes in aflatoxin biosynthesis. Toxins 1: 37–58.

Ehrlich KC and Yu J (2009) Aflatoxin‐like gene clusters and how they evolved. In: Varma AK and Rai MK (eds) Mycotoxins in Food, Feed, and Bioweapons, pp. 65–76. Heidelberg: Springer.

Empting LD (2009) Neurologic and neuropsychiatric syndrome features of mold and mycotoxin exposure. Toxicology and Industrial Health 25: 577–581.

Foroud NA and Eudes F (2009) Trichothecenes in cereal grains. International Journal of Molecular Sciences 10: 147–173.

Gilchrist MA, Sulsky DL and Pringle A (2006) Identifying fitness and optimal life‐history strategies for an asexual filamentous fungus. Evolution 60: 970–979.

Haarmann T, Rolke Y, Giesbert S et al. (2009) Ergot: from witchcraft to biotechnology. Molecular Plant Pathology 10: 563–577.

Hsu IC, Metcalf RA, Sun T et al. (1991) Mutational hotspot in the p53 gene in human hepatocellular carcinomas. Nature 350: 427–428.

Huang XZ, Wang J, Huang C et al. (2008) Emodin enhances cytotoxicity of chemotherapeutic drugs in prostate cancer cells. Cancer Biology & Therapy 7: 468–475.

Karolewiez A and Geisen R (2005) Cloning a part of the ochratoxin A biosynthetic gene cluster of Penicillium nordicum and characterization of the ochratoxin polyketide synthase gene. Systematic and Applied Microbiology 28: 588–595.

Keller NP, Turner G and Bennett JW (2005) Fungal secondary metabolism – from biochemistry to genomics. Nature Reviews. Microbiology 3: 937–947.

Khaldi N, Seifuddin FTGT et al. (2010) SMURF: genomic mapping of fungal secondary metabolite clusters. Fungal Genetic Biology 47: 736–741.

Lorenz N, Haarmann T, Pazoutova S et al. (2009) The ergot alkaloid gene cluster: functional analyses and evolutionary aspects. Phytochemistry 70: 1822–1832.

MacPherson S, Larochelle M and Turcotte B (2006) A fungal family of transcriptional regulators: the zinc cluster proteins. Microbiology and Molecular Biology Reviews 70: 583–604.

Moore GG, Horn BW, Elliott JL et al. (2009) Sexual reproduction influences aflatoxin chemotype diversity in worldwide populations of Aspergillus flavus and A. parasiticus. Phytopathology 99: S88.

Pohland AE and Wood GE (1987) Occurrence of mycotoxins in food. In: Krogh P (ed.) Mycotoxins in Food, pp. 35–64. London: Academic Press.

Rao BL and Husain A (1985) Presence of cyclopiazonic acid in kodo millet (paspalum‐scrobiculatum) causing kodua poisoning in man and its production by associated fungi. Mycopathologia 89: 177–180.

Reddy KRN, Reddy CS, Abbas HK et al. (2008) Mycotoxigenic fungi, mycotoxins, and management of rice grains. Toxin Reviews 27: 287–317.

Reyes‐Dominguez Y, Bok JW, Berger H et al. (2010) Heterochromatic marks are associated with the repression of secondary metabolism clusters in Aspergillus nidulans. Molecular Microbiology 76: 1376–1386.

Richard JL (2007) Some major mycotoxins and their mycotoxicoses – an overview. International Journal of Food Microbiology 119: 3–10.

Rotter BA, Prelusky DB and Pestka JJ (1996) Toxicology of deoxynivalenol (vomitoxin). Journal of Toxicology and Environmental Health 48: 1–34.

Roze LV, Chanda A and Linz JE (2011) Compartmentalization and molecular traffic in secondary metabolism: a new understanding of established cellular processes. Fungal Genetic Biology 48: 35–48.

Sacchi C, Gonzalez HHL, Broggi LE et al. (2009) Fungal contamination and mycotoxin natural occurrence in oats for race horses feeding in Argentina. Animal Feed Science and Technology 152: 330–335.

Scott PM (2009) Ergot alkaloids: extent of human and animal exposure. World Mycotoxin Journal 2: 141–149.

Shephard GS, Berthiller F, Dorner J et al. (2009) Developments in mycotoxin analysis: an update for 2007–2008. World Mycotoxin Journal 2: 3–21.

Stepien L and Chelkowski J (2010) Fusarium head blight of wheat: pathogenic species and their mycotoxins. World Mycotoxin Journal 3: 107–119.

Steyn PS and Stander MA (1999) Mycotoxins as causal factors of diseases in humans. Journal of Toxicology‐Toxin Reviews 18: 229–243.

Stockmann‐Juvala H and Savolainen K (2008) A review of the toxic effects and mechanisms of action of fumonisin B‐1. Human & Experimental Toxicology 27: 799–809.

Stoev SD, Dutton MF, Njobeh PB, Mosonik JS and Steenkamp PA (2010) Mycotoxic nephropathy in Bulgarian pigs and chickens: complex aetiology and similarity to Balkan Endemic Nephropathy. Food Additives and Contaminants Part A‐Chemistry Analysis Control Exposure & Risk Assessment 27: 72–88.

Stratakou I and van der Fels‐Klerx HJ (2010) Mycotoxins in grapes and wine in Europe: occurrence, factors affecting the occurrence and related toxicological effects. World Mycotoxin Journal 3: 283–300.

Straus DC (2009) Molds, mycotoxins, and sick building syndrome. Toxicology and Industrial Health 25: 617–635.

Sugui JA, Pardo J, Chang YC et al. (2007) Gliotoxin is a virulence factor of Aspergillus fumigatus: gliP deletion attenuates virulence in mice immunosuppressed with hydrocortisone Eukaryot. Cell 6: 1562–1569.

Tokai T, Koshino H, Takahashi‐Ando N et al. (2007) Fusarium Tri4 encodes a key multifunctional cytochrome P450 monooxygenase for four consecutive oxygenation steps in trichothecene biosynthesis. Biochemical and Biophysical Research Communications 353: 412–417.

Wu F and Khlangwiset P (2010) Evaluating the technical feasibility of aflatoxin risk reduction strategies in Africa. Food Additives and Contaminants Part A‐Chemistry Analysis Control Exposure & Risk Assessment 27: 658–676.

Wu F, Liu Y and Bhatnagar D (2008) Cost‐effectiveness of aflatoxin control methods: economic incentives. Toxin Reviews 27: 203–225.

Yazar S and Omurtag GZ (2008) Fumonisins, trichothecenes and zearalenone in cereals. International Journal of Molecular Sciences 9: 2062–2090.

Yu J, Chang P‐K, Ehrlich KC et al. (2004) Clustered pathway genes in aflatoxin biosynthesis. Appllied Environmental Microbiology 70: 1253–1262.

Zhou H, Zhan JX, Watanabe K et al. (2008) A polyketide macrolactone synthase from the filamentous fungus Gibberella zeae. Proceedings of the National Academy of Sciences of the USA 105: 6249–6254.

Zhu XC, Vogeler C and Du LC (2008) Functional complementation of fumonisin biosynthesis in FUM1‐disrupted Fusarium verticillioides by the AAL‐toxin polyketide synthase gene ALT1 from Alternaria alternata f. sp lycopersici. Journal of Natural Products 71: 957–960.

Further Reading

Bennett JW and Klich M (2003) Mycotoxins. Clinical Microbiological Review 16: 497–516.

Bhat R, Rai RV and Karim AA (2010) Mycotoxins in food and feed: present status and future concerns. Comprehensive Reviews in Food Science and Food Safety 9: 57–81.

Bohnert M, Wackler B and Hoffmeister D (2010) Spotlights on advances in mycotoxin research. Applied Microbiology and Biotechnology 87: 1–7.

Keller NP, Turner G and Bennett JW (2005) Fungal secondary metabolism – from biochemistry to genomics. Nature Reviews. Microbiology 3: 937–947.

Leslie JF, Bandyopadhyah R and Visconti A (2010) Mycotoxins: Detection Methods, Management, Public Health, and Agricultural Trade. Cambridge, MA: CAB International.

Nevalainen A and Seuri M (2005) Of microbes and men. Indoor Air 15: 58–64.

Palumbo J, O'Keeffe T and Abbas H (2008) Microbial interactions with mycotoxigenic fungi and mycotoxins. Toxin Reviews 27: 261–285.

Rai M and Varma A (2010) Mycotoxins in Food, Feed and Bioweapons. Berlin: Springer.

Shwab EK and Keller NP (2008) Regulation of secondary metabolite production in filamentous ascomycetes. Mycological Research 112: 225–230.

Tirado MC, Clarke R, Jaykus LA et al. (2010) Climate change and food safety: a review. Food Research International 43: 1745–1765.

Wild CP and Gong YY (2010) Mycotoxins and human disease: a largely ignored global health issue. Carcinogenesis 31: 71–82.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Ehrlich, Kenneth C, Chang, Perng‐Kuang, and Bhatnagar, Deepak(Apr 2011) Mycotoxins. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000373.pub2]