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Aflatoxins: Detection, toxicity, and biosynthesis

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Abstract

Aflatoxins are toxic and carcinogenic secondary metabolites produced mainly byAspergillus flavus andAspergillus parasiticus. The aflatoxins present in food and feed are hazardous to both human and animal health. A number of studies have been conducted on the detection, toxicity, biosynthesis, and regulation of aflatoxins due to the discovery of serious aflatoxicosis in farm animals, and the presence of aflatoxins in many food products. There are many reviews that focus on the biosynthesis of aflatoxin, yet there are few examinations of the overall aspects of aflatoxins, including detection, toxicity, and the regulation on biosynthesis. Thus, the goal of this article is to give an overview of the overall aspects of aflatoxins. This review consists of four parts; i) detection methods for aflatoxins, ii) the toxicity mechanism of aflatoxin B1, iii) gene cluster for aflatoxin biosynthesis, and iv) the regulation of aflatoxin biosynthesis.

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References

  1. Kuhn, D. M. and M. A. Ghannoum (2003) Indoor mold, toxigenic fungi, andStachybotrys chartarum: infectious disease perspective.Clin. Microbiol. Rev. 16: 144–172.

    Article  CAS  Google Scholar 

  2. Bhatnagar, D., K. C. Ehrlich, and T. E. Cleveland (2003) Molecular genetic analysis and regulation of aflatoxin biosynthesis.Appl. Microbiol. Biotechnol. 61: 83–93.

    CAS  Google Scholar 

  3. Yabe, K., M. Nakamura, and T. Hamasaki (1999) Enzymatic formation of G-group aflatoxins and biosynthetic relationship between G- and B-group aflatoxins.Appl. Environ. Microbiol. 65: 3867–3872.

    CAS  Google Scholar 

  4. Azziz-Baumgartner, E., K. Lindblade, K. Gieseker, H. S. Rogers, S. Kieszak, H. Njapau, R. Schleicher, L. F. McCoy, A. Misore, I. DeCock, C. Rubin, and L. Slutsker (2005) Case-control study of an acute aflatoxicosis outbreak, Kenya, 2004.Environ. Health Perspect. 113: 1779–1783.

    Article  CAS  Google Scholar 

  5. Coulombe, R. A., Jr. (1993) Biological action of mycotoxins.J. Dairy Sci. 76: 880–891.

    Article  CAS  Google Scholar 

  6. Taggart, P., T. M. Devlin, and J. J. Ch'ih (1986) Multiple aflatoxin B1 binding proteins exist in rat liver cytosol.Proc. Soc. Exp. Biol. Med. 182: 68–72.

    CAS  Google Scholar 

  7. Sabbioni, G., P. L. Skipper, G. Buchi, and S. R. Tanenbaum (1987) Isolation and characterization of the major serum albumin adduct formed by aflatoxin B1in vivo in rats.Carcinogenesis 8: 819–824.

    Article  CAS  Google Scholar 

  8. Sabbinoni, G. (1990) Chemical and physical properties of the major serum-albumin adduct of afflatoxin B1 and their implications for the quantitation in biological samples.Chem. Biol. Interact. 75: 1–15.

    Article  Google Scholar 

  9. Wild, C. P., Y.-Z. Jiang, G. Sabbioni, B. Chapot, and R. Montesano (1990) Evaluation of methods for quantitation of aflatoxin-albumin adducts and their application to human exposure assessment.Cancer Res. 50: 245–251.

    CAS  Google Scholar 

  10. Kärenlampi, S. O. (1987) Mechanism of cytotoxicity of aflatoxin B1: role of cytochrome P1-45.Biochem. Biophys. Res. Commun. 145: 845–860.

    Article  Google Scholar 

  11. Han, E.-M., H. R. Park, S. J. Hu, K.-S. Kwon, H. M. Lee, M.-S. Ha, K.-M. Kim, E.-J. Ko, S.-D. Ha, H. S. Chun, D.-H. Chung, and D.-H. Bae (2006) Monitoring of aflatoxin B1 in livestock feeds using ELISA and HPLC.J. Microbiol. Biotechnol. 16: 643–646.

    CAS  Google Scholar 

  12. Korde, A., S. Banerjee, M. R. A. Pillai, and M. Venkatesh (2001) Preparation and evaluation of125I-aflatoxin B1.J. Radional. Nucl. Chem. 250: 231–237.

    Article  CAS  Google Scholar 

  13. Rhee, J. I., T.-H. Kang, K.-I. Lee, O.-J. Sohn, S.-Y. Kim, and S.-W. Chung (2006) Application of principal component analysis and self-organizing map to the analysis of 2D fluorescence spectra and the monitoring of fermentation processes.Biotechnol. Bioprocess Eng. 11: 432–441.

    Article  CAS  Google Scholar 

  14. Rojas-Durán, T. R., C. A. Fente, B. I. Vázquez, C. M. Franco, A. Sanz-Medel, and A. Cepeda (2007) Study of a room temperature phosphorescence phenomenon to allow the detection of aflatoxigenic strains in culture media.Int. J. Food Microbiol. 115: 149–158.

    Article  CAS  Google Scholar 

  15. Li, G. R., J. J. Wu, W. J. Jin, and J. W. Xie (2003) Antioxygen-quenching room temperature phosphorescence stabilized by deoxycholate aggregate.Talanta 60: 552–562.

    Google Scholar 

  16. Costa-Fernández, J. M. and A. Sanz-Medel (2000) Room temperature phosphorescence (bio)chemical sensors.Quim. Anal. 19: 189–204.

    Google Scholar 

  17. Hwang, S. Y., C. H. Yoo, J. Y. Jeon, S. C. Choi, and E. K. Lee (2005) Quantitative assay of hepatitis B surface antigen by using surface plasmon resonance biosensor.Biotechnol. Bioprocess Eng. 10: 309–314.

    Article  CAS  Google Scholar 

  18. Tripathi, G., H. Li, J. Park, Y. Park, and H. Cheong (2006) Molecular screening and characterization of antiviral potatoes.Biotechnol. Bioprocess Eng. 11: 89–95.

    Article  CAS  Google Scholar 

  19. Kolosova, A. Y., W.-B. Shim, Z.-Y. Yang, S. A. Eremin, and D.-H. Chung (2006) Direct competive ELISA based on a monoclonad antibody for detection of aflatoxin B1. Stabilization of ELISA kit components and application to grain samples.Anal. Bioanal. Chem. 384: 286–294.

    Article  CAS  Google Scholar 

  20. Lee, N. A., S. Wang, R. D. Allan, and I. R. Kennedy (2004) A rapid aflatoxin B1 ELISA: development and validation with reduced matrix effects for peanuts, corn, pistachio, and soybeans.J. Agric. Food Chem. 52: 2746–2755.

    Article  CAS  Google Scholar 

  21. Korde, A., U. Pandey, S. Banerjee, H. D. Sarma, S. Hajare, M. Venkatesh, A. K. Sharma, and M. R. A. Pillai (2003) Development of a radioimmunoassay procedure for aflatoxin B1 measurement.J. Agric. Food Chem. 51: 843–846.

    Article  CAS  Google Scholar 

  22. Garden, S. R. and N. J. C. Strachan (2001) Novel colorimetric immunoassay for the detection of aflatoxin B1.Anal. Chim. Acta 444: 187–191.

    Article  CAS  Google Scholar 

  23. Daly, S. J., G. J. Keating, P. P. Dillon, B. M. Manning, R. O'Kennedy, H. A. Lee, and M. R. A. Morgan (2000) Development of surface plasmon resonance-based immunoassay for aflatoxin B1.J. Agric. Food Chem. 48: 5097–5104.

    Article  CAS  Google Scholar 

  24. Ho, J.-A. A. and R. D. Wauchope (2002) A strip liposome immunoassay for aflatoxin B1.Anal. Chem. 74: 1493–1496.

    Article  CAS  Google Scholar 

  25. Pal, A. and T. K. Dhar (2004) An analytical device for on-site immunoassay. Demonstration of its applicability in semiquantitative detection of aflatoxin B1 in a batch of samples with ultrahigh sensitivity.Anal. Chem. 76: 98–104.

    Article  CAS  Google Scholar 

  26. Nasir, M. S. and M. E. Jolley (2002) Development of a fluorescence polarization assay for the determination of aflatoxins in grains.J. Agric. Food Chem. 50: 3116–3121.

    Article  CAS  Google Scholar 

  27. Arduini, F., I. Errico, A. Amine, L. Micheli, G. Palleschi, and D. Moscone (2007) Enzymatic spectrophotometric method for aflatoxin B detection based on acetylcholinesterase inhibition.Anal. Chem. 79: 3409–3415.

    Article  CAS  Google Scholar 

  28. Forrester, L. M., G. E. Neal, D. J. Judah, M. J. Glancey, and C. R. Wolf (1990) Evidence for involvement of multiple forms of cytochrome P-450 in aflatoxin B1 metabolism in human liver.Proc. Natl. Acad. Sci. USA 87: 8306–8310.

    Article  CAS  Google Scholar 

  29. Shimada, T., S. Nakamura, S. Imaoka, and Y. Funae (1987) Genotoxic and mutagenic activation of aflatoxin B1 by constitutive forms of cytochrome P-450 in rat liver microsomes.Toxicol. Appl. Pharmacol. 91: 13–21.

    Article  CAS  Google Scholar 

  30. Langouët, S., B. Coles, F. Morel, L. Becquemont, P. Beaune, F. P. Guengerich, B. Ketterer, and A. Guillouzo (1995) Inhibition of CYP1A2 and CYP3A4 by oltipraz results in reduction of aflatoxin B1 metabolism in human hepatocytes in primary culture.Cancer Res. 55: 5574–5579.

    Google Scholar 

  31. Langouët, S., K. Mahéo, F. Berthou, F. Morel, D. Lagadic-Gossman, D. Glaise, B. Coles, B. Ketterer, and A. Guillouzo (1997) Effects of administration of the chemoprotective agent oltipraz on CYP1A and CYP2B in rat liver and rat hepatocytes in culture.Carcinogenesis 18: 1343–1349.

    Article  Google Scholar 

  32. Neal, G. E., U. Nielsch, D. J. Judah, and P. B. Hulbert (1987) Conjugation of model substrates or microsomally-activated aflatoxin B1 with reduced glutathione, catalysed by cytosolic glutathione-S-transferases in livers of rats, mice and guinea pigs.Biochem. Pharmacol. 36: 4269–4276.

    Article  CAS  Google Scholar 

  33. Olaniran, A. O., N. H. Mfumo, D. Pillay, and B. Pillay (2006) Synergistic utilization of dichloroethylene as sole carbon source by bacterial consortia isolated from contaminated sites in Africa.Biotechnol. Bioprocess Eng. 11: 205–210.

    Article  CAS  Google Scholar 

  34. Bennett, J. W. and M. Klich (2003) Mycotoxins.Clin. Microbiol. Rev. 16: 497–516.

    Article  CAS  Google Scholar 

  35. Essigmann, J. M., R. G. Croy, R. A. Bennett, and G. N. Wogan (1982) Metabolic activation of aflatoxin B1: patterns of DNA adduct formation, removal, and excretion in relation to carcinogenesis.Drug Metab. Rev. 13: 581–602.

    Article  CAS  Google Scholar 

  36. Chu, Y.-H. and R. Saffhill (1983) Errors in DNA synthesis induced by aflatoxin B1 modification of poly(dC-dG).Carcinogenesis 4: 643–646.

    Article  CAS  Google Scholar 

  37. Guindon, K. A., L. L. Bedard, and T. E. Massey (2007) Elevation of 8-hydroxydeoxyguanosine in DNA from isolated mouse lung cells followingin vivo treatment with aflatoxin B1.Toxicol. Sci. 98: 57–62.

    Article  CAS  Google Scholar 

  38. Bhatnagar, D., K. C. Ehrlich, and T. E. Cleveland (1992) Oxidation-reduction reactions in biosynthesis of secondary metabolites pp. 255–285. In: D. Bhatnagar, E. B. Lillehoj, and D. K. Arora (eds.),Mycotoxins in Ecological Systems. Marcel Dekker, New York, NY, USA.

    Google Scholar 

  39. Brown, D. W., J. H. Yu, H. S. Kelkar, M. Fernandes, T. C. Nesbitt, N. P. Keller, T. H. Adams, and T. J. Leonard (1996) Twenty-five coregulated transcripts define a sterigmatocystin gene cluster inAspergillus nidulans.Proc. Natl. Acad. Sci. USA 93: 1418–1422.

    Article  CAS  Google Scholar 

  40. Carbone, I., J. H. Ramirez-Prado, J. L. Jakobek, and B. W. Horn (2007) Gene duplication, modularity and adaptation in the evolution of the aflatoxin gene cluster.BMC Evol. Biol. 7: 111.

    Article  CAS  Google Scholar 

  41. Yabe, K. and H. Nakajima (2004) Enzyme reactions and genes in aflatoxin biosynthesis.Appl. Microbiol. Biotechnol. 64: 745–755.

    Article  CAS  Google Scholar 

  42. Lee, S.-J., Y.-S. Jeong, D.-U. Kim, J.-W. Seo, and B.-K. Hur (2006) Eicosapentaenoic acid (EPA) biosynthetic gene cluster ofShewanella oneidensis MR-1: cloning, heterologous expression, and effects of temperature and glucose on the production of EPA inEscherichia coli.Biotechnol. Bioprocess Eng. 11: 510–515.

    Article  CAS  Google Scholar 

  43. Trail, F., P. K. Chang, J. Cary, and J. E. Linz (1994) Structural and functional analysis of the nor-1 gene involved in the biosynthesis of aflatoxins byAspergillus parasiticus.Appl. Environ. Microbiol. 60: 4078–4085.

    CAS  Google Scholar 

  44. Sakuno, E., Y. Wen, H. Hatabayashi, H. Arai, C. Aoki, K. Yabe, and H. Nakajima (2005).Aspergillus parasiticus cyclase catalyzes two dehydration steps in aflatoxin biosynthesis.Appl. Environ. Microbiol. 71: 2999–3006.

    Article  CAS  Google Scholar 

  45. Sakuno, E., K. Yabe, and H. Nakajima (2003) Involvement of two cytosolic enzymes and a novel intermediate, 5′-oxoaverantin, in the pathway from 5′-hydroxyaverantin to averufin in aflatoxin biosynthesis.Appl. Environ. Microbiol. 69: 6418–6426.

    Article  CAS  Google Scholar 

  46. McGuire, S. M., J. C. Silva, E. G. Casillas, and C. A. Townsend (1990) Purification and characterization of versicolorin B synthase formAspergillus parasiticus. Catalysis of the stereodifferentiating cyclization in aflatoxin biosynthesis essential to DNA interaction.Biochemistry 35: 11470–11486.

    Article  Google Scholar 

  47. Wen, Y., H. Hatabayashi, H. Arai, H. K. Kitamoto, and K. Yabe (2005) Function of thecypX andmoxY genes in aflatoxin biosynthesis inAspergillus parasiticus.Appl. Environ. Microbiol. 71: 3192–3198.

    Article  CAS  Google Scholar 

  48. Yu, J., C. P. Woloshuk, D. Bhatnagar, and T. E. Cleveland (2000) Cloning and characterization ofavfA andomtB genes involved in aflatoxin biosynthesis in threeAspergillus species.Gene 248: 157–167.

    Article  CAS  Google Scholar 

  49. Yabe, K., Y. Ando, and T. Hamasaki (1991) Desaturase activity in the branching step between aflatoxins B1 and G1 and aflatoxins B2 and G2.Agric. Biol. Chem. 55: 1907–1911.

    CAS  Google Scholar 

  50. Keller, N. P., N. J. Kantz, and T. H. Adams (1994)Aspergillus nidulans verA is required for production of the mycotoxin sterigmatocystin.Appl. Environ. Microbiol. 60: 1444–1450.

    CAS  Google Scholar 

  51. Prieto, R. and C. P. Woloshuk (1997)ordl, an oxidoreductase gene responsible for conversion ofO-methylsterigmatocystin to aflatoxin inAspergillus flavus.Appl. Environ. Microbiol. 63: 1661–1666.

    CAS  Google Scholar 

  52. Yu, J., P.-K. Chang, K. C. Ehrlich, J. W. Cary, D. Bhatnagar, T. E. Cleveland, G. A. Payne, J. E. Linz, C. P. Woloshuk, and J. W. Bennett (2004) Clustered pathway genes in aflatoxin biosynthesis.Appl. Environ. Microbiol. 70: 1253–1262.

    Article  CAS  Google Scholar 

  53. Ehrlich, K. C., P.-K. Chang, J. Yu, and P. J. Cotty (2004) Aflatoxin biosynthesis cluster genecypA is required for G aflatoxin formation.Appl. Environ. Microbiol. 70: 6518–6524.

    Article  CAS  Google Scholar 

  54. Woloshuk, C. P., K. R. Foutz, J. F. Brewer, D. Bhatnagar, T. E. Cleveland, and G. A. Payne (1994) Molecular characterization ofaflR, a regulatory locus for aflatoxin biosynthesis.Appl. Environ. Microbiol. 60: 2408–2414.

    CAS  Google Scholar 

  55. Yu, J.-H., R. A. E. Butchko, M. Fernandes, N. P. Keller, T. J. Leonard, and T. H. Adams (1996) Conservation of structure and function of the aflatoxin regulatory geneaflR fromAspergillus nidulans andA. flavus.Curr. Genet. 29: 549–555.

    Article  CAS  Google Scholar 

  56. Ehrlich, K. C., B. G. Montalbano, D. Bhatnagar, and T. E. Cleveland (1998) Alteration of different domains inaflR affects aflatoxin pathway metabolism inAspergillus parasiticus transformants.Fungal Genet. Biol. 23: 279–287.

    Article  CAS  Google Scholar 

  57. Price, M. S., J. Yu, W. C. Nierman, H. S. Kim, B. Pritchard, C. A. Jacobus, D. Bhatnagar, T. E. Cleveland, and G. A. Payne (2006) The aflatoxin pathway regulator AflR induces gene transcription inside and outside of the aflatoxin biosynthetic cluster.FEMS Microbiol. Lett. 255: 275–279.

    Article  CAS  Google Scholar 

  58. Meyers, D. M., G. Obrian, W. L. Du, D. Bhatnagar, and G. A. Payne (1998) Characterization ofaflJ, a gene required for conversion of pathway intermediates to aflatoxin.Appl. Environ. Microbiol. 64: 3713–3717.

    CAS  Google Scholar 

  59. Yu, J.-H. and N. Keller (2005) Regulation of secondary metabolism in filamentous fungi.Annu. Rev. Phytopathol. 43: 437–458.

    Article  CAS  Google Scholar 

  60. Bok, J. W. and N. P. Keller (2004) LaeA, a regulator of secondary metabolism inAspergillus spp.Eukaryot. Cell 3: 527–535.

    Article  CAS  Google Scholar 

  61. Zhang, Y.-Q., H. Wilkinson, N. P. Keller, and D. Tsitsigiannis (2004) Secondary metabolite gene clusters. pp. 355–386. In: Z. An (ed.)Handbook of Industrial Microbiology. Marcel Dekker, New York, NY, USA.

    Google Scholar 

  62. Perrin, R. M., N. D. Fedorova, J. W. Bok, R. A. Cramer, Jr., J. R. Wortman, H. S. Kim, W. C. Nierman, and N. P. Keller (2007) Transcriptional regulation of chemical diversity inAspergillus fumigatus by LaeA.PloS Pathog. 3: e50.

    Article  CAS  Google Scholar 

  63. Tilburn, J., S. Sarkar, D. A. Widdick, E. A. Espeso, M. Orejas, J. Mungroo, M. A. Penalva and H. N. Arst, Jr. (1995) TheAspergillus PacC zinc finger transcription factor mediates regulation of both acid- and alkaline-expressed genes by ambient pH.EMBO J. 14: 779–790.

    CAS  Google Scholar 

  64. Andrianopoulos, A. and W. E. Timberlake (1994) TheAspergillus nidulans abaA gene encodes a transcriptional activator that acts as a genetic switch to control development.Mol. Cell. Biol. 14: 2503–2515.

    CAS  Google Scholar 

  65. Muro-Pastor, M. I., R. Gonzalez, J. Strauss, F. Narendja, and C. Scazzocchio (1999) The GATA factor AreA is essential for chromatin remodeling in a eukaryotic bidirectional promoter.EMBO J. 18: 1584–1597.

    Article  CAS  Google Scholar 

  66. Bhatnagar, D., J. W. Cary, K. Ehrlich, J. Yu and T. E. Cleveland (2006) Understanding the genetics of regulation of aflatoxin production andAspergillus flavus development.Mycopathologia 162: 155–166.

    Article  CAS  Google Scholar 

  67. Thapar, G. S. (1988) Metabolite behaviour of aflatoxin producing strain and nontoxigenic strain ofAspergillus flavus to different sources of nitrogen and glucose concentration.Mycopathologia 102: 9–12.

    Article  CAS  Google Scholar 

  68. Woloshuk, C. P., J. R. Cavaletto, and T. E. Cleveland (1997) Inducers of aflatoxin biosynthesis from colonized maize kernels are generated by an amylase activity fromAspergillus flavus.Phytopathology 87: 164–169.

    Article  CAS  Google Scholar 

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Do, J.H., Choi, DK. Aflatoxins: Detection, toxicity, and biosynthesis. Biotechnol. Bioprocess Eng. 12, 585–593 (2007). https://doi.org/10.1007/BF02931073

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