Patulin-producing mold, toxicological, biosynthesis, and molecular detection of patulin

Ratih Paramastuti, Winiati Pudji Rahayu, Siti Nurjanah


Mycotoxin is one of the food safety problems that raise concern because of its negative health impact and significant economic losses. Patulin is the most common mycotoxin found in fruits and its products like apple, orange, grape, pear, etc. There are 167 species reported to produce patulin; Penicillium expansum is the major patulin producer among those fungi species. Patulin is not classifiable as to its carcinogenicity to humans, but some studies showed the toxicities of patulin.  Patulin has a broad spectrum of toxicity such as acute toxicity, sub-acute toxicity, genotoxicity, embryotoxicity and teratogenicity, carcinogenicity, and immunotoxicity. There are several ways to detect mycotoxins, such as HPLC, TLC, ELISA, and PCR. The popular way to detect mycotoxin molecularly is PCR because of its sensitivity and specificity. To detect patulin molecularly require proper selection of target gene. Therefore, the biosynthesis of patulin, its influencing gene, and its underlying factor needs to be understood.


Biosynthesis; Molecular detection; Patulin; Toxicological

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Acar, J., Gökmen, V., and Taydas, E. E. (1998) 'The effects of processing technology on the patulin content of juice during commercial apple juice concentrate production', European Food Research and Technology, 207(4), pp. 328-331

Assunção, R., Alvito, P., Kleiveland, C. R., and Lea, T. E. (2016) 'Characterization of in vitro effects of patulin on intestinal epithelial and immune cells', Toxicology Letters, 250–251, pp. 47-56

Ayed-Boussema, I., Abassi, H., Bouaziz, C., Hlima, W. Ben., Ayed, Y., and Bacha, H. (2013) 'Antioxidative and antigenotoxic effect of vitamin E against patulin cytotoxicity and genotoxicity in HepG2 cells', Environmental Toxicology, 28(6), pp. 299-306

Balendres, M. A. O., Karlovsky, P., and Cumagun, C. J. R. (2019) 'Mycotoxigenic fungi and mycotoxins in agricultural crop commodities in the Philippines: A review', Foods, 8(7), pp. 1–12

Biango-Daniels, M. N., Snyder, A. B., Worobo, R. W., and Hodge, K. T. (2019) 'Fruit infected with Paecilomyces niveus: A source of spoilage inoculum and patulin in apple juice concentrate?', Food Control, 97, pp. 81–86

Bissessur, J., Permaul, K., and Odhav, B. (2001) 'Reduction of patulin during apple juice clarification', Journal of Food Protection, 64(8), pp. 1216-1219

Bondy, G. S., and Pestka, J. J. (2005) 'Immunomodulation by fungal toxins', Journal of Toxicology and Environmental Health, 8(3–5), pp. 141–143

Brakhage, A. A. (2013) 'Regulation of fungal secondary metabolism', Nature Reviews Microbiology, 11(1), pp. 21–32

Burroughs, L. F. (1977) 'Stability of patulin to sulfur dioxide and to yeast fermentation', Journal of Association of Official Analytical Chemists, 60(1), pp. 100-103

Chunmei, J., Junling, S., Qi’an, H., and Yanlin, L. (2013) 'Occurrence of toxin-producing fungi in intact and rotten table and wine grapes and related influencing factors', Food Control, 31(1), pp. 5–13

Ciegler, A., Beckwith, A. C., and Jackson, L. K. (1976) 'Teratogenicity of patulin and patulin adducts formed with cysteine', Applied and Environmental Microbiology, 31(5), pp. 664–667

Cubaiu, L., Azara, E., Ladu, G., Venditti, T., and D’Hallewin, G. (2013) 'Native pears of Sardinia affect Penicillium expansum pathogenesis', Communications in Agricultural and Applied Biological Sciences, 78(3), pp. 573-577

Cunha, S. C., Faria, M. A., Pereira, V. L., Oliveira, T. M., Lima, A. C., and Pinto, E. (2014) 'Patulin assessment and fungi identification in organic and conventional fruits and derived products', Food Control, 44, pp. 185–190

De Clercq, N., Vlaemynck, G., Van Pamel, E., Van Weyenberg, S., Herman, L., Devlieghere, F., De Meulenaer, B., and Van Coillie, E. (2016) 'Isoepoxydon dehydrogenase (idh) gene expression in relation to patulin production by Penicillium expansum under different temperature and atmosphere', International Journal of Food Microbiology, 220, pp. 50–57

de Melo, F. T., de Oliveira, I. M., Greggio, S., Dacosta, J. C., Guecheva, T. N., Saffi, J., Henriques, J. A. P., and Rosa, R. M. (2012) 'DNA damage in organs of mice treated acutely with patulin, a known mycotoxin', Food and Chemical Toxicology, 50(10), pp. 3548-3555

Dombrink-Kurtzman, M. A., and Blackburn, J. A. (2005) 'Evaluation of several culture media for production of patulin by Penicillium species', International Journal of Food Microbiology, 98(3), pp. 241–248

Dombrink-Kurtzman, M. A., and Engberg, A. E. (2006) 'Byssochlamys nivea with patulin-producing capability has an isoepoxydon dehydrogenase gene (idh) with sequence homology to Penicillium expansum and P. griseofulvum', Mycological Research, 110(9), pp. 1111–1118

Dombrink-Kurtzman, M. A., and McGovern, A. E. (2007) 'Species-specific identification of Penicillium linked to patulin contamination', Journal of Food Protection, 70(11), pp. 2646–2650

Dombrink-Kurtzman, M. A., and McGovern, A. E. (2016) 'Species-specific identification of penicillium linked to patulin contamination', Journal of Food Protection, 70(11), pp. 2646–2650

El Hajj Assaf, C., Snini, S. P., Tadrist, S., Bailly, S., Naylies, C., Oswald, I. P., Lorber, S., and Puel, O. (2018) 'Impact of veA on the development, aggressiveness, dissemination and secondary metabolism of Penicillium expansum', Molecular Plant Pathology, 19(8), pp. 1971-1983

El Sheikha, A. F. (2019) 'Molecular detection of mycotoxigenic fungi in foods: the case for using PCR-DGGE', Food Biotechnology, 33(1), pp. 54–108

European Commision. (2006) 'Commission regulation (EC) No 1881/2006 of 19 december 2006 setting maximum levels for certain contaminants in foodstuffs', Official Journal of the European Union, 364, pp. 5-24

Fedeshko, R. W. (1992) Polyketide enzymes and genes in Penicillium urticae. Canada: University of Calgary.

Frisvad, J. C. (2018) 'A critical review of producers of small lactone mycotoxins: patulin, penicillic acid and moniliformin', World Mycotoxin Journal, 11(1), pp. 73–100

Funes, G. J., Gómez, P. L., Resnik, S. L., and Alzamora, S. M. (2013) 'Application of pulsed light to patulin reduction in McIlvaine buffer and apple products', Food Control, 30(2), pp. 405–410

Glaser, N., and Stopper, H. (2012) 'Patulin: Mechanism of genotoxicity', Food and Chemical Toxicology, 50(5), pp. 1796–1801

Gökmen, V., Artik, N., Acar, J., Kahraman, N., and Poyrazoĝlu, E. (2001) 'Effects of various clarification treatments on patulin, phenolic compound and organic acid compositions of apple juice', European Food Research and Technology, 213(3), pp. 194-199

Guerra-Moreno, A., and Hanna, J. (2017) 'Induction of proteotoxic stress by the mycotoxin patulin', Toxicology Letters, 276, pp. 85-91

Hao, H., Zhou, T., Koutchma, T., Wu, F., and Warriner, K. (2016) 'High hydrostatic pressure assisted degradation of patulin in fruit and vegetable juice blends', Food Control, 62, pp. 237-242

Hatab, S., Yue, T., and Mohamad, O. (2012) 'Reduction of patulin in aqueous solution by lactic acid bacteria', Journal of Food Science, 77(4), pp. 238-241

Huffman, J., Gerber, R., and Du, L. (2010) 'Review recent advancements in the biosynthetic mechanisms for polyketide-derived mycotoxins', Biopolymers, 93(9), pp. 764-776

Hussain, S., Asi, M. R., Iqbal, M., Khalid, N., Wajih-Ul-Hassan, S., and Ariño, A. (2020) 'Patulin mycotoxin in mango and orange fruits, juices, pulps, and jams marketed in Pakistan', Toxins, 12(1), pp. 1–10

IARC. (1987) An updating of IARC monographs Volumes 1 to Supplement. France: IARC Publications.

Ioi, J. D., Zhou, T., Tsao, R., and Marcone, M. F. (2017) 'Mitigation of patulin in fresh and processed foods and beverages', Toxins, 9(5), pp. 1–18

Jayashree, G. V., Krupashree, K., Rachitha, P., and Khanum, F. (2017) 'Patulin induced oxidative stress mediated apoptotic damage in mice, and its modulation by green tea leaves', Journal of Clinical and Experimental Hepatology, 7(2), pp. 127-134

Kadakal, C., and Nas, S. (2003) 'Effect of heat treatment and evaporation on patulin and some other properties of apple juice', Science of Food and Agriculture, 83(9), pp. 987–990

Keller, N. P. (2015) 'Translating biosynthetic gene clusters into fungal armor and weaponry', Nature Chemical Biology, 11(9), pp. 671–677

Konietzny, U., and Greiner, R. (2003) 'The application of PCR in the

detection of mycotoxigenic fungi in foods', Brazilian Journal of Microbiology, 34(4), pp. 283–300

Kubacki, S. (1986) 'The analysis and occurrence of patulin in apple juice', Mycotoxins and Phytotoxins, 1, pp. 293-304

Li, B., Chen, Y., Zhang, Z., Qin, G., Chen, T., and Tian, S. (2020) 'Molecular basis and regulation of pathogenicity and patulin biosynthesis in Penicillium expansum', Comprehensive Reviews in Food Science and Food Safety, 19(6), pp. 3416-3438

Li, B., Chen, Y., Zong, Y., Shang, Y., Zhang, Z., Xu, X., Wang, X., Long, M., and Tian, S. (2019) 'Dissection of patulin biosynthesis, spatial control and regulation mechanism in Penicillium expansum', Environmental Microbiology, 21(3), pp. 1124–1139

Li, B., Zong, Y., Du, Z., Chen, Y., Zhang, Z., Qin, G., Zhao, W., and Tian, S. (2015) 'Genomic characterization reveals insights into patulin biosynthesis and pathogenicity in Penicillium species', Molecular Plant-Microbe Interactions, 28(6), pp. 635–647

Luque, M. I., Andrade, M. J., Rodríguez, A., Bermúdez, E., and Córdoba, J. J. (2013) 'Development of a multiplex PCR method for the detection of patulin-, ochratoxin a- and aflatoxin-producing moulds in foods', Food Analytical Methods, 6(4), pp. 1113–1121

Luque, M. I., Rodríguez, A., Andrade, M. J., Gordillo, R., Rodríguez, M., and Córdoba, J. J. (2011) 'Development of a PCR protocol to detect patulin producing moulds in food products', Food Control, 22(12), pp. 1831–1838

Macheleidt, J., Mattern, D. J., Fischer, J., Netzker, T., Weber, J., Schroeckh, V., Valiante, V., and Brakhage, A. A. (2016) 'Regulation and Role of Fungal Secondary Metabolites', Annual Review of Genetics, 50, pp. 371–392

Maidana, L., Gerez, J. R., El Khoury, R., Pinho, F., Puel, O., Oswald, I. P., and Bracarense, A. P. F. R. L. (2016) 'Effects of patulin and ascladiol on porcine intestinal mucosa: An ex vivo approach', Food and Chemical Toxicology, 98, pp. 189–194

Marin, S., Ramos, A. J., and Sanchis, V. (2013) 'Mycotoxins : Occurrence , toxicology , and exposure assessment', Food and Chemical Toxicology, 60, pp. 218–237

Matthiaschk, G., and Korte, A. (1986) 'Studies on the embryotoxicity and mutagenicity of mycotoxins', Mycotoxin Research, 2(2),pp. 89-97

McKinley, E. R., and Carlton, W. W. (1980) 'Patulin mycotoxicosis in the Syrian hamster', Food and Cosmetics Toxicology, 18(2), pp. 173-179

McKinley, E. R., Carlton, W. W., and Boon, G. D. (1982) 'Patulin mycotoxicosis in the rat: Toxicology, pathology and clinical pathology', Food and Chemical Toxicology, 20(3), pp. 289-300

Moake, M. M., Padilla-zakour, O. I., and Worobo, R. W. (2005) 'Comprehensive review of patulin control methods in foods industry', Comprehensive Reviews in Food Science and Food Safety, 1, pp. 8-21

Mostafa, A., Armin, A., Hamid, P., and Reza, A. M. (2012) 'Rapid detection methods for analysis of fungi and mycotoxins in agriculture products', Research Journal of Recent Sciences, 1(7), pp. 90–98

Munaut, F., Van Hove, F., and Moretti, A. (2011) Molecular identification of mycotoxigenic fungi in food and feed. determining mycotoxins and mycotoxigenic fungi in food and feed. United Kingdom: Woodhead Publishing.

Pal, S., Singh, N., and Ansari, K. M. (2017) 'Toxicological effects of patulin mycotoxin on the mammalian system: An overview', Toxicology Research, 6(6), pp. 764–771

Paterson, R. R. M. (2004) 'The isoepoxydon dehydrogenase gene of patulin biosynthesis in cultures and secondary metabolites as candidate PCR inhibitors', Mycological Research, 108(12), pp. 1431–1437

Paterson, R. R. M. (2007) 'The isoepoxydon dehydrogenase gene PCR profile is useful in fungal taxonomy', Revista Iberoamericana de Micologia, 24(4), pp. 289–293

Puel, O., Galtier, P., and Oswald, I. (2010) 'Biosynthesis and Toxicological Effects of Patulin', Toxins, 2(4), pp. 613–631

Rahayu, W. P., Nurjanah, S., Mutaqin, L., Dewi, A. S., and Paramastuti, R. (2019) 'Diversity of mold contaminants in tropical fruits', Prosiding Seminar Nasional Teknologi Pangan dan Gizi, pp. 117–134 [In Indonesian]

Raja, H. A., Miller, A. N., Pearce, C. J., and Oberlies, N. H. (2017) 'Fungal identification using molecular tools: a primer for the natural products research community', Journal of Natural Products, 80(3), pp. 756–770

Ramalingam, S., Bahuguna, A., and Kim, M. (2019) 'The effects of mycotoxin patulin on cells and cellular components', Trends in Food Science and Technology, 83,pp. 99–113

Reddy, C. S., Chan, P. K., and Hayes, A. W. (1978) 'Teratogenic and dominant lethal studies of patulin in mice', Toxicology, 11, pp. 219–223

Richard, G. F., Kerrest, A., and Dujon, B. (2008) 'Comparative genomics and molecular dynamics of DNA repeats in eukaryotes', Microbiology and Molecular Biology Reviews, 72(4), pp. 686–727

Rodríguez, A., Isabel Luque, M., Andrade, M. J., Rodríguez, M., Asensio, M. A., and Córdoba, J. J. (2011) 'Development of real-time PCR methods to quantify patulin-producing molds in food products', Food Microbiology, 28(6), pp. 1190–1199

Rodríguez, A., Rodríguez, M., Andrade, M. J., and Córdoba, J. J. (2012) 'Development of a multiplex real-time PCR to quantify aflatoxin, ochratoxin A and patulin producing molds in foods', International Journal of Food Microbiology, 155(1–2), pp. 10–18

Saleh, I., and Goktepe, I. (2019) 'The characteristics, occurrence, and toxicological effects of patulin', Food and Chemical Toxicology, 129, pp. 301–311

Saxena, N., Ansari, K. M., Kumar, R., Dhawan, A., Dwivedi, P. D., and Das, M. (2009) 'Patulin causes DNA damage leading to cell cycle arrest and apoptosis through modulation of Bax, p53 and p21/WAF1 proteins in skin of mice', Toxicology and Applied Pharmacology, 234(2), pp. 192-201

Selmanoǧlu, G. (2006) 'Evaluation of the reproductive toxicity of patulin in growing male rats', Food and Chemical Toxicology, 44(12), pp.2019-2024

Sharma, R. P. (1993) 'Immunotoxicity of mycotoxins', Journal of Dairy Science, 76(3), pp. 892–897

Snini, S. P., Tannous, J., Heuillard, P., Bailly, S., Lippi, Y., Zehraoui, E., Barreau, C., Oswald, I. P., and Puel, O. (2016) 'Patulin is a cultivar-dependent aggressiveness factor favouring the colonization of apples by Penicillium expansum', Molecular Plant Pathology, 17(6), pp. 920–930

Song, E., Xia, X., Su, C., Dong, W., Xian, Y., Wang, W., and Song, Y. (2014) 'Hepatotoxicity and genotoxicity of patulin in mice, and its modulation by green tea polyphenols administration', Food and Chemical Toxicology, 71, pp. 122-127

Tannous, J., Atoui, A., El Khoury, A., Francis, Z., Oswald, I. P., Puel, O., and Lteif, R. (2016) 'A study on the physicochemical parameters for Penicillium expansum growth and patulin production: effect of temperature, pH, and water activity', Food Science and Nutrition, 4(4), pp. 611–622

Tannous, J., Atoui, A., El Khoury, A., Kantar, S., Chdid, N., Oswald, I. P., Puel, O., and Lteif, R. (2015) 'Development of a real-time PCR assay for Penicillium expansum quantification and patulin estimation in apples', Food Microbiology, 50, pp. 28–37

Tannous, J., El Khoury, R., Snini, S. P., Lippi, Y., El Khoury, A., Atoui, A., Lteif, R., Oswald, I. P., and Puel, O. (2014) 'Sequencing, physical organization and kinetic expression of the patulin biosynthetic gene cluster from Penicillium expansum', International Journal of Food Microbiology, 189, pp. 51–60

Tapia, M. O., Stern, M. D., Soraci, A. L., Meronuck, R., Olson, W., Gold, S., Koski-Hulbert, R. L., and Murphy, M. J. (2005) 'Patulin-producing molds in corn silage and high moisture corn and effects of patulin on fermentation by ruminal microbes in continuous culture', Animal Feed Science and Technology, 119(3–4), pp. 247–258

Tikekar, R. V, Anantheswaran, R. C., and Laborde, L. F. (2014) 'Patulin degradation in a model apple juice system and in apple juice during ultraviolet processing', Journal of Food Procesing and Preservation, 38(3), pp. 924–934

Tola, M., and Kebede, B. (2016) 'Occurrence, importance and control of mycotoxins: A review', Cogent Food & Agriculture, 2(1), pp. 1-12

Ur Rahman, H., Yue, X., Yu, Q., Zhang, W., Zhang, Q., and Li, P. (2020) 'Current PCR-based methods for the detection of mycotoxigenic fungi in complex food and feed matrices', World Mycotoxin Journal, 13(2), pp. 139–150

Wei, C., Yu, L., Qiao, N., Zhao, J., Zhang, H., Zhai, Q., Tian, F., and Chen, W. (2020) 'Progress in the distribution, toxicity, control, and detoxification of patulin: A review', Toxicon, 184,pp. 83–93

Welke, J. E., Hoeltz, M., Dottori, H. A., and Noll, I. B. (2010) 'Fungi and patulin in apples and the role of processing on patulin levels in juices: A study on naturally contaminated apples', Journal of Food Safety, 30(2), pp. 276–287

Alkhayyat, F., and Yu, J. H. (2014) Upstream regulation of mycotoxin biosynthesis. Amsterdam: Elsevier Publishing

Zhang, B., Peng, X., Li, G., Xu, Y., Xia, X., and Wang, Q. (2015) 'Oxidative stress is involved in Patulin induced apoptosis in HEK293 cells', Toxicon, 94, pp. 1–7

Zong, Y., Li, B., and Tian, S. (2015) 'Effects of carbon, Nitrogen and ambient pH on patulin production and related gene expression in Penicillium expansum', International Journal of Food Microbiology, 206, pp. 102–108.



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