Biosynthesis and toxicological effects of patulin

Toxins

Volumn 2, Issue 4, 2010, Pages 613-631

  Puel, Olivier ^a   Galtier, Pierre ^a   Oswald, Isabelle P ^a  

^a CEMAGREF   (France)

Author keywords

Biosynthesis; Patulin; Polyketide; Toxicity

Indexed keywords

PATULIN;

ACUTE TOXICITY; ASPERGILLUS; BIOSYNTHESIS; BYSSOCHLAMYS; CARCINOGENICITY; EMBRYOTOXICITY; ENZYME ACTIVITY; FOOD CONTAMINATION; FUNGAL GENE; FUNGAL METABOLISM; GENE CLUSTER; GENOTOXICITY; IMMUNOTOXICITY; NEUROTOXICITY; NONHUMAN; PAECILOMYCES; PENICILLIUM; REVIEW; TERATOGENICITY;

ABNORMALITIES, DRUG-INDUCED; ANIMALS; FETUS; HUMANS; IMMUNE SYSTEM; MULTIGENE FAMILY; PATULIN;

ASPERGILLUS; BYSSOCHLAMYS; MALUS X DOMESTICA; PENICILLIUM;

EID: 78650213047     PISSN: None     EISSN: 20726651     Source Type: Journal    
DOI: 10.3390/toxins2040613     Document Type: Review

References (107)

1. Birkinshaw, J.H; Michael, S.E.; Bracken, A.; Raistrick, H. Patulin in the common cold collaborative research on a derivative of Penicillium patulum Bainier. II. Biochemistry and Chemistry. Lancet 1943, 245, 625.
2. Chalmers, I.; Clarke, M. Commentary: The 1944 patulin trial: The first properly controlled multicentre trial conducted under the aegis of the British Medical Research Council. Int. J. Epidemiol. 2004, 33, 253-260.
3. European Union. Commission Regulation (EC) No. 1425/2003 of 11 August 2003 amending Regulation (EC) N°466/2001 as regards patulin. Official J. European Union L 203/13.
4. Moake, M.M.; Padilla-Zakour, O.I.; Worobo, R.W. Comprehensive review of patulin control methods in foods. Compr. Rev. Food Sci. Food Saf. 2005, 1, 8-21.
5. Varga, J.; Due, M.; Frisvad, J.C.; Samson, R.A. Taxonomic revision of Aspergillus section Clavati based on molecular, morphological and physiological data. Stud. Mycol. 2007, 59, 89-106.
6. Frisvad, J.C.; Smedsgaard, J.; Larsen, T.O.; Samson, R.A. Mycotoxins, drugs and other extrolites produced by species in Penicillium subgenus Penicillium. Stud. Mycol. 2004, 49, 201-242.
7. Houbraken, J.; Samson, R.A.; Frisvad, J.C. Byssochlamys: Significance of heat resistance and mycotoxin production. Adv. Exp. Med. Biol. 2006, 571, 211-224.
8. Puel, O.; Tadrist, S.; Delaforge, M.; Oswald, I.P.; Lebrihi, A. The inability of Byssochlamys fulva to produce patulin is related to absence of 6-methylsalicylic acid synthase and isoepoxydon dehydrogenase genes. Int. J. Food Microbiol. 2007, 115, 131-139.
9. Samson, R.A.; Houbraken, J.; Varga, J; Frisvad J.C. Polyphasic taxonomy of the heat resistant ascomycete genus Byssochlamys and its Paecilomyces anamorphs. Persoonia 2009, 22, 14-27.
10. McKinley, E.R.; Carlton, W.W. Patulin. In Mycotoxins and Phytoalexins; Sharma, R.P., Salunkhe, D.K., Eds.; CRC Press: Boca Raton, FL, USA, 1991; pp. 191-236.
11. Birch A.J.; Massy-Westrop R.A.; Moye C.J. Studies in relation to biosynthesis. VII. 2-Hydroxy-6-methylbenzoic acid in Penicillium griseofulvum Dierckx. Aust. J. Chem. 1955, 8, 539-544.
12. Lynen, F.; Tada, M. Die biochemischen grundlagen der polyacetat-regel. Angew. Chem. 1961, 73, 513-519.
13. Sekiguchi, J.; Gaucher G.M. Conidiogenesis and secondary metabolism in Penicillium urticae. Appl. Environ. Microbiol. 1977, 33, 147-158.
14. Beck, J.; Ripka, S.; Siegner, A.; Schiltz, E.; Schweizer, E. The multifunctional 6-methylsalicylic acid synthase gene of Penicillium patulum. Its gene structure relative to that of other polyketide synthases. Eur. J. Biochem. 1990, 192, 487-498.
15. Wang, I.K.; Reeves, C.; Gaucher, G.M. Isolation and sequencing of a genomic DNA clone containing the 3' terminus of the 6-methylsalicylic acid polyketide synthetase gene of Penicillium urticae. Can. J. Microbiol. 1991, 37, 86-95.
16. Spencer, J.B.; Jordan, P.M. Purification and properties of 6-methylsalicylic acid synthase from Penicillium patulum. Biochem. J. 1992, 288, 839-846.
17. Bu'Lock, J.D.; Ryan, A.J. The biogenesis of patulin. Proc. Chem. Soc. 1958, 222-223.
18. Tanenbaum, S.W.; Bassett, E.W. The biosynthesis of patulin. III. Evidence for a molecular rearrangement of the aromatic ring. J. Biol. Chem. 1959, 234, 1861-1866.
19. Forrester, P.I.; Gaucher, G.M. Conversion of 6-methylsalicylic acid into patulin by Penicillium urticae. Biochemistry 1972, 11, 1102-1107.
20. Scott, A.I.; Zamir, L.; Phillips, G.T.; Yalpani, M. The biosynthesis of patulin. Bioorg. Chem. 1973, 2, 124-139.
21. Scott, A.I.; Yalpani M. A mass-spectrometric study of biosynthesis: Conversion of deuteron-m-cresol into patulin. Chem. Commun. 1967, 18, 945-946.
22. Sekiguchi, J.; Gaucher, G.M. Isoepoxydon, a new metabolite of the patulin pathway in Penicillium urticae. Biochem. J. 1979, 182, 445-453.
23. Sekiguchi, J.; Gaucher, G.M. Identification of phyllostine as an intermediate of the patulin pathway in Penicillium urticae. Biochemistry 1978, 17, 1785-1791.
24. Sekiguchi, J.; Gaucher, G.M.; Yamada Y. Biosynthesis of patulin in Penicillum urticae: Identification of isopatulin as a new intermediate. Tetrahedron Lett. 1979, 1, 41-42.
25. Sekiguchi, J.; Shimamoto, T.; Yamada, Y.; Gaucher, G.M. Patulin biosynthesis: enzymatic and nonenzymatic transformations of the mycotoxin (E)-ascladiol. Appl. Environ. Microbiol. 1983, 45, 1939-1942.
26. Priest, J.W; Light, R.J. Patulin biosynthesis: epoxidation of toluquinol and gentisyl alcohol by particulate preparations from Penicillium patulum. Biochemistry 1989, 28, 9192-9200.
27. Murphy, G.; Lynen, F. Patulin biosynthesis: The metabolism of m-hydroxybenzyl alcohol and m-hydroxybenzaldehyde by particulate preparations from Penicillium patulum. Eur. J. Biochem. 1975, 58, 467-475.
28. Light R.J. 6-methylsalicylic acid decarboxylase from Penicillium patulum. Biochim. Biophys. Acta 1969, 191, 430-438.
29. Fedeshko, R.W. Polyketide enzymes and genes in Penicillium urticae. PhD thesis, University of Calgary, Calgary, Alberta, Canada, 1992.
30. Keller, N.P.; Hohn, T.M. Metabolic pathway gene clusters in filamentous fungi. Fungal Genet. Biol. 1997, 21, 17-29.
31. Keller, N.P.; Turner, G.; Bennett, J.W. Fungal secondary metabolism - from biochemistry to genomics. Nat. Rev. Microbiol. 2005, 3, 937-947.
32. Yu, J.; Chang, P.K.; Ehrlich, K.C.; Cary, J.W.; Bhatnagar, D.; Cleveland, T.E.; Payne, G.A.; Linz, J.E.; Woloshuk C.P.; Bennett, J.W. Clustered pathway genes in aflatoxin biosynthesis. Appl. Environ. Microbiol. 2004, 70, 1253-1262.
33. Seo, J.A.; Proctor, R.H.; Plattner, R.D. Characterization of four clustered and coregulated genes associated with fumonisin biosynthesis in Fusarium verticillioides. Fungal Genet. Biol. 2001, 34,155-165.
34. Kimura, M.; Tokai, T.; Takahashi-Ando, N.; Ohsato, S.; Fujimura, M. Molecular and genetic studies of Fusarium trichothecene biosynthesis: Pathways, genes, and evolution. Biosci. Biotechnol. Biochem. 2007, 71, 2105-2123.
35. Kim, Y.T.; Lee, Y.R.; Jin, J.; Han, K.H.; Kim, H.; Kim, J.C.; Lee, T.; Yun, S.H.; Lee, Y.W. Two different polyketide synthase genes are required for synthesis of zearalenone in Gibberella zeae. Mol. Microbiol. 2005, 58, 1102-1113.
36. Dombrink-Kurtzman, M.A. The isoepoxydon dehydrogenase gene of the patulin metabolic pathway differs for Penicillium griseofulvum and Penicillium expansum. Antonie Van Leeuwenhoek 2006, 89, 1-8.
37. Dombrink-Kurtzman, M.A. The sequence of the isoepoxydon dehydrogenase gene of the patulin biosynthetic pathway in Penicillium species. Antonie Van Leeuwenhoek 2007, 91,179-189.
38. White, S.; O'Callaghan, J.; Dobson, A.D. Cloning and molecular characterization of Penicillium expansum genes upregulated under conditions permissive for patulin biosynthesis. FEMS Microbiol. Lett. 2006, 255, 17-26.
39. Dombrink-Kurtzman, M.A.; Engberg, A.E. Byssochlamys nivea with patulin-producing capability has an isoepoxydon dehydrogenase gene (idh) with sequence homology to Penicillium expansum and P. griseofulvum. Mycol. Res. 2006, 110, 1111-1118.
40. Dombrink-Kurtzman, M.A. A gene having sequence homology to isoamyl alcohol oxidase is transcribed during patulin production in Penicillium griseofulvum. Curr. microbiol.2008, 56, 224-228.
41. Artigot, M.P.; Loiseau, N.; Laffitte, J.; Mas-Reguieg, L.; Tadrist, S.; Oswald, I.P.; Puel, O. Molecular cloning and functional characterization of two CYP619 cytochrome P450s involved in biosynthesis of patulin in Aspergillus clavatus. Microbiology 2009, 155, 1738-1747.
42. Varga, J.; Tóth, B.; Kocsubé, S.; Farkas, B.; Szakács, G.; Téren, J.; Kozakiewicz, Z. Evolutionary relationships among Aspergillus terreus isolates and their relatives. Antonie Van Leeuwenhoek 2005, 88, 141-150.
43. Fujii, I.; Ono, Y.; Tada, H.; Gomi, K.; Ebizuka, Y.; Sankawa, U. Cloning of the polyketide synthase gene atX from Aspergillus terreus and its identification as the 6-methylsalicylic acid synthase gene by heterologous expression. Mol. Gen. Genet. 1996, 253, 1-10.
44. Read G.; Westlake, D.W.; Vining, L.C. Quinone epoxides V The biosynthesis of terreic acid. Can. J. Biochem.1969, 47, 1071-1079.
45. Liu A.; Zhang H. Transition metal-catalyzed nonoxidative decarboxylation reactions. Biochemistry 2006, 45, 10407-10411.
46. Chanda A.; Roze, L.V.; Kang, S., Artymovich, K.A., Hicks, G.R., Raikhel, N.V.; Calvo, A.M.; Linz, J.E. A key role for vesicles in fungal secondary metabolism. Proc. Natl. Acad. Sci. USA 2009, 106, 19533-19538.
47. Grootwassink, J.W.; Gaucher, G.M. De novo biosynthesis of secondary metabolism enzymes in homogeneous cultures of Penicillium urticae. J. Bacteriol. 1980, 141, 443-455.
48. Rollins, M.J.; Gaucher, G.M. Ammonium repression of antibiotic and intracellular proteinase production in Penicillium urticae. Appl. Microbiol. Biotechnol. 1994, 41, 447-455.
49. Feng, G.H.; Leonard, T.J. Culture conditions control expression of the genes for aflatoxin and sterigmatocystin biosynthesis in Aspergillus parasiticus and A. nidulans. Appl. Environ. Microbiol. 1998, 64, 2275-2277.
50. Abbas, A., Valez, H.; Dobson, A.D. Analysis of the effect of nutritional factors on OTA and OTB biosynthesis and polyketide synthase gene expression in Aspergillus ochraceus. Int. J. Food Microbiol. 2009, 135, 22-27.
51. Summerer, S.M. A study of fungal polyketide gene expression and isolation. PhD thesis, University of Calgary, Calgary, Alberta, Canada, 1996.
52. Ellis, C.M. Regulation of polyketide gene expression: The isolation and function of nitrogen regulatory factor, NRFA from Penicillium urticae. PhD thesis, University of Calgary, Calgary, Alberta, Canada, 1996.
53. Scott, R.E.; Jones, A.; Lam, K.S.; Gaucher, G.M. Manganese and antibiotic biosynthesis. I. A specific manganese requirement for patulin production in Penicillium urticae. Can. J. Microbiol. 1986, 32, 259-267.
54. Scott, R.E.; Jones, A.; Gaucher, G.M. Manganese and antibiotic biosynthesis. III. The site of manganese control of patulin production in Penicillium urticae. Can. J. Microbiol. 1986, 32, 273-279.
55. Gaucher, G.M.; Lam, K.S.; Grootwassink, J.W.D.; Neway, J.; Deo Y.M. The initiation and longevity of patulin biosynthesis. Dev. Industr. Microbiol. 1981, 22, 219-232.
56. McKinley, E.R.; Carlton, W.W. Patulin mycotoxicosis in Swiss ICR mice. Food Cosmet. Toxicol. 1980, 18, 181-187.
57. McKinley, E.R.; Carlton, W.W. Patulin mycotoxicosis in the Syrian hamster. Food Cosmet. Toxicol. 1980, 18, 173-179.
58. McKinley, E.R.; Carlton, W.W.; Boon, G.D. Patulin mycotoxicosis in the rat: Toxicology, pathology and clinical pathology. Food Chem. Toxicol. 1982, 20, 289-300.
59. WHO. Joint FAO/WHO Expert Committee on Food additives (JECFA), Position paper on patulin, 30th session, The Hague, The Netherlands, 9-13 March, 1998.
60. Hayes, A.W.; Phillips, T.D.; Williams, W.L.; Ciegler, A. Acute toxicity of patulin in mice and rats. Toxicology 1979, 13, 91-100.
61. Ciegler, A.; Beckwith, A.C.; Jackson, L.K. Teratogenicity of patulin and patulin adducts formed with cysteine. Appl. Environ. Microbiol. 1976, 31, 664-667.
62. Speijers, G.J.A.; Kolkman, R.; Franken, M.A.M.; Van Leeuwen, F.X.R.; Danse, L.H.J.C. Subacute toxiciteit van patulin in de rat. Rapport nr. 617903 001. Rijksinstituut voor Volksgezondheid en Milieuhygiëne, 1985.
63. Speijers, G.J.A.; Franken, M.A.M.; Van Leeuwen, F.X.R.; Van Egmond, H.P.; Boot, R.; Loeber, J.G. Subchronic oral toxicity study of patulin in the rat. Report no. 618314 001. Rijksinstituut voor Volksgezondheid en Milieuhygiëne, 1986.
64. Devaraj, H.; Suseela, R.E.; Devaraj, N. Patulin toxicosis in chicks. Curr. Sci. 1986, 55, 998-999.
65. Devaraj, H.; Devaraj, N. Rat intestinal lipid changes in patulin toxicity. Indian J. of Exp. Biol. 1987, 25, 637-638.
66. Garza, H.C.; Swanson, B.G.; Branen, A.L. Toxicology study of patulin in monkeys. J. Food Sci. 1977, 42, 1229-1231.
67. Selmanoglu, G.; Kockaya, E.A. Investigation of the effects of patulin on thyroid and testis, and hormone levels in growing male rats. Food Chem. Toxicol. 2004, 42, 721-727.
68. Selmanoglu, G. Evaluation of the reproductive toxicity of patulin in growing male rats. Food Chem. Toxicol. 2006, 44, 2019-2024.
69. Wurgler, F.E.; Friederich, U.; Schlatter, J. Lack of mutagenicity of ochratoxin A and B, citrinin, patulin and cnestine in Salmonella typhimurium TAI02. Mutat. Res. 1991, 261, 209-216.
70. IARC. Some Naturally Occurring and Synthetic Food Components, Furocoumarins and Ultraviolet Radiation. In Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans; IARC: Lyon, France, 1986; pp. 83-98.
71. Sakai, M.; Abe, K.; Okumura, H.; Kawamura, O.; Sugiura, Y.; Horie, Y.; Ueno, Y. Genotoxicity of fungi evaluated by SOS microplate assay. Nat. Toxins 1992, 1, 27-34.
72. Hradec, J.; Vesely, D. The initiator tRNA acceptance assay as a short-term test for carcinogens. Carcinogenesis 1989. 10, 213-215.
73. Thust, R.; Kneist, S.; Mendel, J. Patulin, a further clastogenic mycotoxin, is negative in the SCE assay in Chinese hamster V79-E cells in vitro. Mutat. Res. 1982, 103, 91-97.
74. Pfeiffer, E.; Gross, K.; Metzler, M. Aneuploidogenic and clastogenic potential of the mycotoxins citrinin and patulin. Carcinogenesis 1998, 19, 1313-1318.
75. Alves, I.; Oliveira, N.G.; Laires, A.; Rodrigues, A.S.; Rueff, J. Induction of micronuclei and chromosomal aberrations by the mycotoxin patulin in mammalian cells: role of ascorbic acid as a modulator of patulin clastogenicity. Mutagenesis 2000, 15, 229-234.
76. Umeda, M.; Tsutsui, T.; Saito, M. Mutagenicity and inducibility of DNA single-strand breaks and chromosome aberrations by various mycotoxins. Gann 1977, 68, 619-625.
77. Schumacher, D.M.; Metzler, M.; Lehmann, L. Mutagenicity of the mycotoxin patulin in cultured Chinese hamster V79 cells, and its modulation by intracellular glutathione. Arch. Toxicol. 2005, 79, 110-121.
78. Schumacher, D.M.; Wagner, J.; Metzler, M.; Lehmann, L. Influence of decreased intracellular glutathione level on the mutagenicity of patulin in cultured mouse lymphoma cells. Mycotoxin Res. 2005, 21, 150-152.
79. Liu, B.H.; Yu, F.Y.; Wu, T.S.; Li, S.Y.; Su, M.C.; Wang, M.C.; Shih, S.M. Evaluation of genotoxic risk and oxidative DNA damage in mammalian cells exposed to mycotoxins, patulin and citrinin. Toxicol. Appl. Pharmacol. 2003, 191, 255-263.
80. Liu, B.H.; Wu, T.S.; Yu, F.Y.; Su, C.C. Induction of oxidative stress response by the mycotoxin patulin in mammalian cells. Toxicol. Sci. 2007, 95, 340-347.
81. Riley, R.T.; Showker, J.L. The mechanism of patulin's cytotoxicity and the antioxidant activity of indole tetramic acids. Toxicol. Appl. Pharmacol. 1991, 109, 108-126.
82. Osswald, H.; Frank, H.K.; Komitowski, D.; Winter, H. Long-term testing of patulin administered orally to Sprague-Dawley rats and Swiss mice. Food Cosmet. Toxicol. 1978, 16, 243-247.
83. Becci, P.J.; Hess, F.G.; Johnson, W.D.; Gallo, M.A.; Babish, J.G.; Dailey, R.E.; Parent, R.A. Long-term carcinogenicity and toxicity studies of patulin in the rat. J. Appl. Toxicol. 1981, 1, 256-261.
84. Dailey, R.E., Brouwer, E.; Blaschka, A.M.; Reynaldo, E.F.; Green, S.; Monlux, W.S.; Ruggles, D.I. Intermediate-duration toxicity study of patulin in rats. J. Toxicol. Environ. Health. 1977, 2, 713-725.
85. Reddy, C.S.; Chan, P.K.; Hayes, A.W. Teratogenic and dominant lethal studies of patulin in mice. Toxicology 1978, 11, 219-223.
86. Roll, R.; Matthiaschk, G.; Korte, A. Embryotoxicity and mutagenicity of mycotoxins. J. Environ. Pathol. Toxicol. Oncol. 1990, 10, 1-7.
87. Smith, E.E.; Duffus, E.A.; Small, M.H. Effects of patulin on postimplantation rat embryos. Arch. Environ. Contam. Toxicol. 1993, 25, 267-270.
88. Oswald, I.P.; Comera, C. Immunotoxicity of mycotoxins. Rev. Med. Vet. 1998, 149, 585-590.
89. Sorenson, W.G.; Gerberick, G.F.; Lewis, D.M.; Castranova, V. Toxicity of mycotoxins for the rat pulmonary macrophage in vitro. Env. Health Persp. 1986, 66, 45-53.
90. Bourdiol, D.; Escoula, L.; Salvayre, R. Effect of patulin on microbicidal activity of mouse peritoneal macrophages. Food Chem. Toxicol. 1990, 28, 29-33.
91. Wichmann, G.; Herbarth, O.; Lehmann I. The mycotoxins citrinin, gliotoxin, and patulin affect interferon-gamma rather than interleukin-4 production in human blood cells. Environ. Toxicol. 2002, 17, 211-218.
92. Luft, P.; Oostingh, G.J.; Gruijthuijsen, Y.; Horejs-Hoeck, J.; Lehmann, I.; Duschl, A. Patulin Influences the Expression of Th1/Th2 Cytokines by Activated Peripheral Blood Mononuclear Cells and T Cells Through Depletion of Intracellular Glutathione. Environ. Toxicol. 2008, 23, 84-95.
93. Marin, M.L.; Murtha, J.; Dong, W.; Pestka, J.J. Effects of mycotoxins on cytokine production and proliferation in EL-4 thymoma cells. J. Toxicol. Environ. Health. 1996, 48, 379-396.
94. Escoula, L.; Thomsen, M.; Bourdiol, D.; Pipy, B.; Peuriere, S.; Roubinet, S. Patulin immunotoxicology: Effect on phagocyte activation and the cellular and humoral immune system of mice and rabbits. Int. J. Immunopharmacol. 1988, 10, 983-989.
95. Paucod, J.C.; Krivobok, S.; Vidal, D. Immunotoxicity testing of mycotoxins T-2 and patulin on Balb/c mice. Acta Microbiol. Hung. 1990, 37, 331-339.
96. Escoula, L.; Bourdiol, D.; Linas, M.D.; Recco, P.; Seguela, J.P. Enhancing resistance and modulation of humoral immune response to experimental Candida albicans infection by patulin. Mycopathologia 1988, 103, 153-156.
97. Llewellyn, G.C.; McCay, J.A.; Brown, R.D.; Musgrove, D.L.; Butterworth, L.F.; Munson, A.E.; White, K.L., Jr. Immunological evaluation of the mycotoxin patulin in female B6C3F1 mice. Food Chem. Toxicol. 1998, 36, 1107-1111.
98. Mahfoud, R.; Maresca, M., Garmy, N.; Fantini, J. The mycotoxin patulin alters the barrier function of the intestinal epithelium: Mechanism of action of the toxin and protective effects of glutathione. Toxicol. Appl. Pharmacol. 2002, 181, 209-218.
99. Maresca, M.; Yahi, N.; Younès-Sakr, L.; Boyron, M.; Caporiccio, B.; Fantini, J. Both direct and indirect effects account for the pro-inflammatory activity of enteropathogenic mycotoxins on the human intestinal epithelium: Stimulation of interleukin-8 secretion, potentiation of interleukin-1beta effect and increase in the transepithelial passage of commensal bacteria. Toxicol. Appl. Pharmacol. 2008, 228, 84-92.
100. Bouhet, S.; Oswald, I.P. The effects of mycotoxins, fungal food contaminants, on the intestinal epithelial cell-derived innate immune response. Vet. Immunol. Immunopathol. 2005, 108, 199-209.
101. Bouhet, S.; Hourcade, E.; Loiseau, N.; Fikry, A.; Martinez, S.; Roselli, M.; Galtier, P.; Mengheri, E.; Oswald I.P. The mycotoxin fumonisin B1 alters the proliferation and the barrier function of porcine intestinal epithelial cells. Toxicol. Sci. 2004, 77, 165-171.
102. Pinton, P.; Nougayrède, J.P.; Del Rio, J.C.; Moreno, C.; Marin, D.E.; Ferrier, L.; Bracarense, A.P.; Kolf-Clauw, M.; Oswald, I.P. The food contaminant deoxynivalenol, decreases intestinal barrier permeability and reduces claudin expression. Toxicol. Appl. Pharmacol. 2009, 237, 41-48.
103. Bayram, O.; Krappmann, S.; Ni, M.; Bok, J.W.; Helmstaedt, K.; Valerius, O.; Braus-Stromeyer, S.; Kwon, N.J.; Keller, N.P.; Yu, J.H.; Braus, G.H. VelB/VeA/LaeA complex coordinates light signal with fungal development and secondary metabolism. Science 2008, 320, 1504-1506.
104. Duran, R.M.; Cary, J.W.; Calvo, A.M. Production of cyclopiazonic acid, aflatrem, and aflatoxin by Aspergillus flavus is regulated by veA, a gene necessary for sclerotial formation. Appl. Microbiol. Biotechnol. 2007, 73, 1158-1168.
105. Myung, K.; Li, S.; Butchko, R.A.; Busman, M.; Proctor, R.H.; Abbas H.K.; Calvo, A.M. FvVE1 regulates biosynthesis of the mycotoxins fumonisins and fusarins in Fusarium verticillioides. J. Agric. Food Chem. 2009, 57, 5089-5094.
106. Bok, J.W.; Keller, N.P. LaeA, a regulator of secondary metabolism in Aspergillus spp. Eukaryot. Cell 2004, 3, 527-535.
107. Priest, J.W.; Light, R.J. Applications of high-performance liquid chromatography to quantitation of metabolites and enzymes of the patulin pathway from Penicillium patulum. J. Chromatogr. 1990, 513, 237-246.