Knowledge on the functions, cooperation, and interplays of the signaling and regulatory pathways of filamentous fungi is crucial when their industrial performance is improved or when new-type antifungals are developed. Many research groups aim at a deeper understanding of vegetative growth signaling because this cascade also influences other important physiological processes including asexual and sexual developments, autolysis and apoptotic cell death as well as the production of a wide array of important secondary metabolites. This review also focuses on how this signaling pathway is interconnected with other signaling cascades setting up a robust but delicately regulated signaling network in the Aspergilli. 1. Introduction Almost 50% of the known fungi and around 80% of the human pathogen fungi are phylogenetically related to Ascomycetes [1]. Moreover, many species of the Aspergilli possess medical and/or industrial importance; for example, they have large capacities of extracellular hydrolytic enzyme, food ingredient, or antibiotic productions [2]. Considering the most studied species within this genus, Aspergillus niger can play a role as an opportunistic pathogen in humans [3], though its real importance is in industrial-scale citric acid production [4], which is higher than one million tons per year [5]. A. oryzae is a well-known “generally regarded as safe” (GRAS) organism in food fermentation industry, for example, in traditional sake, tofu, and acetic acid productions. A. fumigatus is a specialized opportunistic human pathogen, which is a saprophytic organism [6–8] with air-spread conidiospores [9, 10]. It is characterized by abundant spore production as, from every conidiophore, thousands of small (2-3？μm diameters) conidia are released and are able to reach the alveoli in lungs [11]. With increase in number of immunosuppressed patients and modern immunosuppressing therapies [12–14], this fungus became very dangerous especially in developing countries [15–19]. Although A. fumigatus is considered as the most dangerous fungus causing higher than 90% of human aspergilloses [8, 20–24], other species are also potential pathogens; for example, A. flavus, A. terreus, A. niger and even A. nidulans can also cause human illnesses [24]. Moreover, A. nidulans is a well-known genetic model organism within the Aspergilli with an enormous background database (http://www.aspgd.org/) on its genetic and biochemical properties. 2. Vegetative Growth Signaling The growth of A. nidulans is regulated via the FadA-dependent signal transduction pathway, where FadA is
References
[1]
J. Guarro, J. Gené, and A. M. Stchigel, “Developments in fungal taxonomy,” Clinical Microbiology Reviews, vol. 12, no. 3, pp. 454–500, 1999.
[2]
C. Knuf and J. Nielsen, “Aspergilli: systems biology and industrial applications,” Biotechnology Journal, vol. 7, pp. 1147–1155, 2012.
[3]
J. R. Perfect, G. M. Cox, J. Y. Lee et al., “The impact of culture isolation of Aspergillus species: a hospital-based survey of aspergillosis,” Clinical Infectious Diseases, vol. 33, no. 11, pp. 1824–1833, 2001.
[4]
J. Magnuson and L. Lasure, “Organic acid production by filamentous fungi,” in Advances in Fungal Biotechnology for Industry, Agriculture, and Medicine, J. Tkacz and L. Lange, Eds., pp. 307–340, Kluwer Academic & Plenum, New York, NY, USA, 2004.
[5]
S. E. Baker, “Aspergillus niger genomics: past, present and into the future,” Medical Mycology, vol. 44, no. 1, pp. 17–21, 2006.
[6]
H. van den Bossche, D. W. R. MacKenzie, and G. Cauwenbergh, Eds., Aspergillus and Aspergillosis, Plenum Press, New York, NY, USA, 1988.
[7]
J. I. Pitt, “The current role of Aspergillus and Penicillium in human and animal health,” Journal of Medical and Veterinary Mycology, Supplement, vol. 32, supplement 1, pp. 17–32, 1994.
[8]
J. Haines, “Aspergillus in compost: straw man or fatal flaw,” BioCycle, vol. 6, pp. 32–35, 1995.
[9]
J. Mullins, R. Harvey, and A. Seaton, “Sources and incidence of airborne Aspergillus fumigatus (Fres),” Clinical Allergy, vol. 6, no. 3, pp. 209–217, 1976.
[10]
J. Mullins, P. S. Hutcheson, and R. G. Slavin, “Aspergillus fumigatus spore concentration in outside air: Cardiff and St Louis compared,” Clinical Allergy, vol. 14, no. 4, pp. 351–354, 1984.
[11]
R. A. Samson and E. S. van Reenen-Hoekstra, Eds., Introduction to Food-Borne Fungi: Centraalbureau Voor Schimmelcultures, Baarn, The Netherlands, 1988.
[12]
J. Cohen, D. W. Dennining, and M. A. Viviani, “Epidemiology of invasive aspergillosis in European cancer centres,” European Journal of Clinical Microbiology and Infectious Diseases, vol. 12, no. 5, pp. 392–393, 1993.
[13]
T. R. Rogers, “Epidemiology and control of nosocomial fungal infections,” Current Opinion in Infectious Diseases, vol. 8, no. 4, pp. 287–290, 1995.
[14]
R. Ruchlemer, A. M. Yinnon, and C. Hershko, “Changes in the natural history of invasive pulmonary aspergillosis in neutropenic leukemic patients,” Israel Journal of Medical Sciences, vol. 32, no. 11, pp. 1089–1092, 1996.
[15]
G. P. Bodey and S. Vartivarian, “Aspergillosis,” European Journal of Clinical Microbiology and Infectious Diseases, vol. 8, no. 5, pp. 413–437, 1989.
[16]
V. T. Andriole, “Infections with Aspergillus species,” Clinical Infectious Diseases, vol. 17, no. 2, pp. S481–S486, 1993.
[17]
D. M. Dixon, M. M. McNeil, M. L. Cohen, B. G. Gellin, and J. R. La Montagne, “Fungal infections: a growing threat,” Public Health Reports, vol. 111, no. 3, pp. 226–235, 1996.
[18]
A. H. Groll, P. M. Shah, C. Mentzel, M. Schneider, G. Just-Nuebling, and K. Huebner, “Trends in the postmortem epidemiology of invasive fungal infections at a University Hospital,” Journal of Infection, vol. 33, no. 1, pp. 23–32, 1996.
[19]
D. W. Denning, “Invasive aspergillosis,” Clinical Infectious Diseases, vol. 26, no. 4, pp. 781–805, 1998.
[20]
V. P. Kurup and A. Kumar, “Immunodiagnosis of aspergillosis,” Clinical Microbiology Reviews, vol. 4, no. 4, pp. 439–456, 1991.
[21]
D. D. Dixon and T. J. Walsh, “Human pathogenesis,” in Aspergillus, Biology and Industrial Application, J. W. Bennett and M. A. Klich, Eds., pp. 249–267, Butterworth-Heinemann, Boston, Mass, USA, 1992.
[22]
A. Schaffner, “Host defense in aspergillosis,” in New Strategies in Fungal Disease, J. E. Bennett, R. J. Hay, and P. K. Peterson, Eds., pp. 98–112, Churchill Livingstone, Edinburgh, UK, 1992.
[23]
F. Derouin, “Diagnosis, treatment and prevention of invasive aspergillosis. A priority target in hospital units,” Pathologie Biologie, vol. 42, no. 7, pp. 629–631, 1994.
[24]
J. Latgé, “Aspergillus fumigatus and aspergillosis,” Clinical Microbiology Reviews, vol. 12, no. 2, pp. 310–350, 1999.
[25]
J. Seo, K. Han, and J. Yu, “Multiple roles of a heterotrimeric G-protein γ-subunit in governing growth and development of Aspergillus nidulans,” Genetics, vol. 171, no. 1, pp. 81–89, 2005.
[26]
J. Yu, “Heterotrimeric G protein signaling and RGSs in Aspergillus nidulans,” Journal of Microbiology, vol. 44, no. 2, pp. 145–154, 2006.
[27]
S. Rosén, J. Yu, and T. H. Adams, “The Aspergillus nidulans sfaD gene encodes a G protein β subunit that is required for normal growth and repression of sporulation,” The EMBO Journal, vol. 18, no. 20, pp. 5592–5600, 1999.
[28]
K. Shimizu and N. P. Keller, “Genetic involvement of a cAMP-dependent protein kinase in a G protein signaling pathway regulating morphological and chemical transitions in Aspergillus nidulans,” Genetics, vol. 157, no. 2, pp. 591–600, 2001.
[29]
H. S. Park and J. H. Yu, “Genetic control of asexual sporulation in filamentous fungi,” Current Opinion in Microbiology, vol. 15, pp. 669–677, 2012.
[30]
J. Yu, J. Wieser, and T. H. Adams, “The Aspergillus FlbA RGS domain protein antagonizes G protein signaling to block proliferation and allow development,” The EMBO Journal, vol. 15, no. 19, pp. 5184–5190, 1996.
[31]
K. S. Shin, H. S. Park, Y. H. Kim, and J. H. Yu, “Comparative proteomic analyses reveal that FlbA down-regulates gliT expression and SOD activity in Aspergillus fumigatus,” Journal of Proteomics, vol. 87, pp. 40–52, 2013.
[32]
J. Seo and J. Yu, “The phosducin-like protein PhnA is required for Gβγ-mediated signaling for vegetative growth, developmental control, and toxin biosynthesis in Aspergillus nidulans,” Eukaryotic Cell, vol. 5, no. 2, pp. 400–410, 2006.
[33]
T. H. Adams, J. K. Wieser, and J. Yu, “Asexual sporulation in Aspergillus nidulans,” Microbiology and Molecular Biology Reviews, vol. 62, no. 1, pp. 35–54, 1998.
[34]
P. Krijgsheld, R. Bleichrodt, G. J. van Veluw et al., “Development in Aspergillus,” Studies in Mycology, vol. 74, pp. 1–29, 2013.
[35]
U. Kües and R. Fischer, “Asexual sporulation in mycelial fungi,” in The Mycota: Growth, Differentiation and Sexuality, U. Kües and R. Fischer, Eds., vol. 1, pp. 263–292, Springer, 2006.
[36]
H. Yang and G. B. Lucas, “Effects of N2-O2 and CO2-O2 tensions on growth of fungi isolated from damaged flue-cured tobacco,” Applied Microbiology, vol. 19, no. 2, pp. 271–277, 1970.
[37]
A. M. Calvo, “The VeA regulatory system and its role in morphological and chemical development in fungi,” Fungal Genetics and Biology, vol. 45, no. 7, pp. 1053–1061, 2008.
[38]
I. Skromne, O. Sanchez, and J. Aguirre, “Starvation stress modulates the expression of the Aspergillus nidulans brlA regulatory gene,” Microbiology, vol. 141, no. 1, pp. 21–28, 1995.
[39]
O. Etxebeste, E. Herrero-García, L. Araújo-Bazán et al., “The bZIP-type transcription factor FIbB regulates distinct morphogenetic stages of colony formation in Aspergillus nidulans,” Molecular Microbiology, vol. 73, no. 5, pp. 775–789, 2009.
[40]
T. Emri, Z. Molnár, M. Szilágyi, and I. Pócsi, “Regulation of autolysis in Aspergillus nidulans,” Applied Biochemistry and Biotechnology, vol. 151, no. 2-3, pp. 211–220, 2008.
[41]
T. H. Adams, M. T. Boylan, and W. E. Timberlake, “brlA is necessary and sufficient to direct conidiophore development in Aspergillus nidulans,” Cell, vol. 54, no. 3, pp. 353–362, 1988.
[42]
A. Andrianopoulos and W. E. Timberlake, “The Aspergillus nidulans abaA gene encodes a transcriptional activator that acts as a genetic switch to control development,” Molecular and Cellular Biology, vol. 14, no. 4, pp. 2503–2515, 1994.
[43]
T. C. Sewall, C. W. Mims, and W. E. Timberlake, “abaA controls phialide differentiation in Aspergillus nidulans,” Plant Cell, vol. 2, no. 8, pp. 731–739, 1990.
[44]
P. M. Mirabito, T. H. Adams, and W. E. Timberlake, “Interactions of three sequentially expressed genes control temporal and spatial specificity in Aspergillus development,” Cell, vol. 57, no. 5, pp. 859–868, 1989.
[45]
M. T. Boylan, P. M. Mirabito, C. E. Willett, C. R. Zimmerman, and W. E. Timberlake, “Isolation and physical characterization of three essential conidiation genes from Aspergillus nidulans,” Molecular and Cellular Biology, vol. 7, no. 9, pp. 3113–3118, 1987.
[46]
O. Etxebeste, A. Garzia, E. A. Espeso, and U. Ugalde, “Aspergillus nidulans asexual development: making the most of cellular modules,” Trends in Microbiology, vol. 18, no. 12, pp. 569–576, 2010.
[47]
P. Xiao, K. Shin, T. Wang, and J. Yu, “Aspergillus fumigatus flbB encodes two basic leucine zipper domain (bZIP) proteins required for proper asexual development and gliotoxin production,” Eukaryotic Cell, vol. 9, no. 11, pp. 1711–1723, 2010.
[48]
O. Etxebeste, M. Ni, A. Garzia et al., “Basic-zipper-type transcription factor FlbB controls asexual development in Aspergillus nidulans,” Eukaryotic Cell, vol. 7, no. 1, pp. 38–48, 2008.
[49]
N. Kwon, A. Garzia, E. A. Espeso, U. Ugalde, and J. Yu, “FlbC is a putative nuclear C2H2 transcription factor regulating development in Aspergillus nidulans,” Molecular Microbiology, vol. 77, no. 5, pp. 1203–1219, 2010.
[50]
J. Arratia-Quijada, O. Sánchez, C. Scazzocchio, and J. Aguirre, “FlbD, a Myb transcription factor of Aspergillus nidulans, is uniquely involved in both asexual and sexual differentiation,” Eukaryotic Cell, vol. 11, pp. 1132–1142, 2012.
[51]
J. Wieser and T. H. Adams, “flbD encodes a Myb-like DNA-binding protein that coordinates initiation of Aspergillus nidulans conidiophore development,” Genes and Development, vol. 9, no. 4, pp. 491–502, 1995.
[52]
N. Kwon, K. Shin, and J. Yu, “Characterization of the developmental regulator FlbE in Aspergillus fumigatus and Aspergillus nidulans,” Fungal Genetics and Biology, vol. 47, no. 12, pp. 981–993, 2010.
[53]
A. Garzia, O. Etxebeste, E. Herrero-Garcia, R. Fischer, E. A. Espeso, and U. Ugalde, “Aspergillus nidulans FlbE is an upstream developmental activator of conidiation functionally associated with the putative transcription factor FlbB,” Molecular Microbiology, vol. 71, no. 1, pp. 172–184, 2009.
[54]
S. Jain and N. Keller, “Insights to fungal biology through LaeA sleuthing,” Fungal Biology Reviews, vol. 27, pp. 51–59, 2013.
[55]
S. S. Kim, Y. H. Kim, and K. S. Shin, “The developmental regulators, FlbB and FlbE, are involved in the virulence of Aspergillus fumigatus,” Journal of Microbiology and Biotechnology, vol. 23, pp. 766–770, 2013.
[56]
J. Wieser, B. N. Lee, J. W. Fondon III, and T. H. Adams, “Genetic requirements for initiating asexual development in Aspergillus nidulans,” Current Genetics, vol. 27, no. 1, pp. 62–69, 1994.
[57]
J. Mah and J. Yu, “Upstream and downstream regulation of asexual development in Aspergillus fumigatus,” Eukaryotic Cell, vol. 5, no. 10, pp. 1585–1595, 2006.
[58]
J. H. Yu, “Regulation and development of Aspergillus nidulans and Aspergillus fumigatus,” Mycobiology, vol. 38, pp. 229–237, 2010.
[59]
M. Ogawa, M. Tokuoka, F. J. Jin, T. Takahashi, and Y. Koyama, “Genetic analysis of conidiation regulatory pathways in koji-mold Aspergillus oryzae,” Fungal Genetics and Biology, vol. 47, no. 1, pp. 10–18, 2010.
[60]
M. E. D. S. Ferreira, T. Heinekamp, A. H？rtl et al., “Functional characterization of the Aspergillus fumigatus calcineurin,” Fungal Genetics and Biology, vol. 44, no. 3, pp. 219–230, 2007.
[61]
F. M. Soriani, I. Malavazi, M. E. Da Silva Ferreira et al., “Functional characterization of the Aspergillus fumigatus CRZ1 homologue, CrzA,” Molecular Microbiology, vol. 67, no. 6, pp. 1274–1291, 2008.
[62]
A. Spielvogel, H. Findon, H. N. Arst Jr. et al., “Two zinc finger transcription factors CrzA and SltA, are involved in cation homoeostasis and detoxification in Aspergillus nidulans,” Biochemical Journal, vol. 414, no. 3, pp. 419–429, 2008.
[63]
R. S. Almeida, O. Loss, A. C. Colabardini, et al., “Genetic bypass of Aspergillus nidulanscrzA function in calcium homeostasis,” Genes-Genomes-Genetics, vol. 3, pp. 1129–1141, 2013.
[64]
P. K. Chang, “Aspergillus parasiticus crzA, which encodes calcineurin response zinc-finger protein, is required for aflatoxin production under calcium stress,” International Journal of Molecular Science, vol. 9, pp. 2027–2043, 2008.
[65]
R. A. Cramer Jr., B. Z. Perfect, N. Pinchai et al., “Calcineurin target CrzA regulates conidial germination, hyphal growth, and pathogenesis of Aspergillus fumigatus,” Eukaryotic Cell, vol. 7, no. 7, pp. 1085–1097, 2008.
[66]
？. Bayram, G. H. Braus, R. Fischer, and J. Rodriguez-Romero, “Spotlight on Aspergillus nidulans photosensory systems,” Fungal Genetics and Biology, vol. 47, no. 11, pp. 900–908, 2010.
[67]
J. Rodriguez-Romero, M. Hedtke, C. Kastner, S. Müller, and R. Fischer, “Fungi, hidden in soil or up in the air: light makes a difference,” Annual Review of Microbiology, vol. 64, pp. 585–610, 2010.
[68]
C. Ruger-Herreros, J. Rodríguez-Romero, R. Fernández-Barranco et al., “Regulation of conidiation by light in Aspergillus nidulans,” Genetics, vol. 188, no. 4, pp. 809–822, 2011.
[69]
H. Jeong, H. Kim, D. Han, K. Jahng, and K. Chae, “Expression of the mnpA gene that encodes the mannoprotein of Aspergillus nidulans is dependent on fadA and flbA as well as veA,” Fungal Genetics and Biology, vol. 38, no. 2, pp. 228–236, 2003.
[70]
B. N. Lee and T. H. Adams, “The Aspergillus nidulans fluG gene is required for production of an extracellular developmental signal and is related to prokaryotic glutamine synthetase I,” Genes and Development, vol. 8, no. 6, pp. 641–651, 1994.
[71]
A. B. Rodríguez-Urra, C. Jiménez, M. I. Nieto, J. Rodríguez, H. Hayashi, and U. Ugalde, “Signaling the induction of sporulation involves the interaction of two secondary metabolites in Aspergillus nidulans,” ACS Chemical Biology, vol. 7, no. 3, pp. 599–606, 2012.
[72]
G. Soid-Raggi, O. Sánchez, and J. Aguirre, “TmpA, a member of a novel family of putative membrane flavoproteins, regulates asexual development in Aspergillus nidulans,” Molecular Microbiology, vol. 59, no. 3, pp. 854–869, 2006.
[73]
L. N. Yager, H. Lee, D. L. Nagle, and J. E. Zimmerman, “Analysis of fluG mutations that affect light-dependent conidiation in Aspergillus nidulans,” Genetics, vol. 149, no. 4, pp. 1777–1786, 1998.
[74]
J. L. Mooney, D. E. Hassett, and L. N. Yager, “Genetic analysis of suppressors of the veA1 mutation in Aspergillus nidulans,” Genetics, vol. 126, no. 4, pp. 869–874, 1990.
[75]
P. K. Chang, L. L. Scharfenstein, B. Mack, and K. C. Ehrlich, “Deletion of the Aspergillus flavus orthologue of A. nidulans fluG reduces conidiation and promotes production of sclerotia but does not abolish aflatoxin biosynthesis,” Applied Environmental Microbiology, vol. 78, pp. 7557–7563, 2012.
[76]
J. Seo, Y. Guan, and J. Yu, “FluG-dependent asexual development in Aspergillus nidulans occurs via derepression,” Genetics, vol. 172, no. 3, pp. 1535–1544, 2006.
[77]
K. Han, J. Seo, and J. Yu, “Regulators of G-protein signalling in Aspergillus nidulans: RgsA downregulates stress response and stimulates asexual sporulation through attentuation of GanB (Gα) signalling,” Molecular Microbiology, vol. 53, no. 2, pp. 529–540, 2004.
[78]
N. J. Kwon, H. S. Park, S. Jung, S. C. Kim, and J. H. Yu, “The putative guanine nucleotide exchange factor RicA mediates upstream signaling for growth and development in Aspergillus,” Eukaryotic Cell, vol. 11, pp. 1399–1412, 2012.
[79]
T. H. Adams, W. A. Hide, L. N. Yager, and B. N. L. Bee Na Lee, “Isolation of a gene required for programmed initiation of development by Aspergillus nidulans,” Molecular and Cellular Biology, vol. 12, no. 9, pp. 3827–3833, 1992.
[80]
B. M. Nitsche, T. R. J？rgensen, M. Akeroyd, V. Meyer, and A. F. J. Ram, “The carbon starvation response of Aspergillus niger during submerged cultivation: insights from the transcriptome and secretome,” BMC Genomics, vol. 13, article 380, 2012.
[81]
M. Szilágyi, M. Miskei, Z. Karányi, B. Lenkey, I. Pócsi, and T. Emri, “Transcriptome changes initiated by carbon starvation in Aspergillus nidulans,” Microbiology, vol. 159, pp. 176–190, 2013.
[82]
B. N. Lee and T. H. Adams, “Overexpression of flbA, an early regulator of Aspergillus asexual sporulation, leads to activation of brlA and premature initiation of development,” Molecular Microbiology, vol. 14, no. 2, pp. 323–334, 1994.
[83]
S. P. Champe, D. L. Nagle, and L. N. Yager, “Sexual sporulation,” Progress in Industrial Microbiology, vol. 29, pp. 429–454, 1994.
[84]
H. Kim, K. Chae, K. Han, and D. Han, “The nsdC gene encoding a putative C2H2-type transcription factor is a key activator of sexual development in Aspergillus nidulans,” Genetics, vol. 182, no. 3, pp. 771–783, 2009.
[85]
K. Han, K. Han, J. Yu, K. Chae, K. Jahng, and D. Han, “The nsdD gene encodes a putative GATA-type transcription factor necessary for sexual development of Aspergillus nidulans,” Molecular Microbiology, vol. 41, no. 2, pp. 299–309, 2001.
[86]
J. W. Cary, P. Y. Harris-Coward, K. C. Ehrlich et al., “NsdC and NsdD affect Aspergillus flavus morphogenesis and aflatoxin production,” Eukaryotic Cell, vol. 11, pp. 1104–1111, 2012.
[87]
K. Han, J. H. Kim, H. Moon et al., “The Aspergillus nidulans esdC (early sexual development) gene is necessary for sexual development and is controlled by veA and a heterotrimeric G protein,” Fungal Genetics and Biology, vol. 45, no. 3, pp. 310–318, 2008.
[88]
B. Levine and D. J. Klionsky, “Development by self-digestion: molecular mechanisms and biological functions of autophagy,” Developmental Cell, vol. 6, no. 4, pp. 463–477, 2004.
[89]
T. Emri, Z. Molnár, and I. Pócsi, “The appearances of autolytic and apoptotic markers are concomitant but differently regulated in carbon-starving Aspergillus nidulans cultures,” FEMS Microbiology Letters, vol. 251, no. 2, pp. 297–303, 2005.
[90]
T. Yorimitsu and D. J. Klionsky, “Autophagy: molecular machinery for self-eating,” Cell Death and Differentiation, vol. 12, no. 2, pp. 1542–1552, 2005.
[91]
D. L. Richie and D. S. Askew, “Autophagy in the filamentous fungus Aspergillus fumigatus,” Methods in enzymology, vol. 451, pp. 241–250, 2008.
[92]
M. McIntyre, D. R. Berry, and B. McNeil, “Response of Penicillium chrysogenum to oxygen starvation in glucose- and nitrogen-limited chemostat cultures,” Enzyme and Microbial Technology, vol. 25, no. 3-5, pp. 447–454, 1999.
[93]
B. M. Nitsche, A. M. Burggraaf-van Welzen, G. Lamers, V. Meyer, and A. F. Ram, “Autophagy promotes survival in aging submerged cultures of the filamentous fungus Aspergillus niger,” Applied Microbiology and Biotechnology, 2013.
[94]
S. White, M. McIntyre, D. R. Berry, and B. McNeil, “The autolysis of industrial filamentous fungi,” Critical Reviews in Biotechnology, vol. 22, no. 1, pp. 1–14, 2002.
[95]
T. Emri, Z. Molnár, T. Pusztahelyi, and I. Pócsi, “Physiological and morphological changes in autolyzing Aspergillus nidulans cultures,” Folia Microbiologica, vol. 49, no. 3, pp. 277–284, 2004.
[96]
T. Emri, Z. Molnár, T. Veres, T. Pusztahelyi, G. Dudás, and I. Pócsi, “Glucose-mediated repression of autolysis and conidiogenesis in Emericella nidulans,” Mycological Research, vol. 110, no. 10, pp. 1172–1178, 2006.
[97]
T. Pusztahelyi, I. Pócsi, J. Kozma, and A. Szentirmai, “Aging of Penicillium chrysogenum cultures under carbon starvation: I: morphological changes and secondary metabolite production,” Biotechnology and Applied Biochemistry, vol. 25, no. 1, pp. 81–86, 1997.
[98]
I. Pócsi, T. Pusztahelyi, L. Sámi, and T. Emri, “Autolysis of Penicillium chrysogenum—a holistic approach,” Indian Journal of Biotechnology, vol. 2, no. 3, pp. 293–301, 2003.
[99]
R. A. Shroff, S. M. O'Connor, M. J. Hynes, R. A. Lockington, and J. M. Kelly, “Null alleles of creA, the regulator of carbon catabolite repression in Aspergillus nidulans,” Fungal Genetics and Biology, vol. 22, no. 1, pp. 28–38, 1997.
[100]
J. O. Nehlin and H. Ronne, “Yeast MIG1 repressor is related to the mammalian early growth response and Wilms' tumour finger proteins,” The EMBO Journal, vol. 9, no. 9, pp. 2891–2898, 1990.
[101]
M. Mathieu and B. Felenbok, “The Aspergillus nidulans CREA protein mediates glucose repression of the ethanol regulon at various levels through competition with the ALCR-specific transactivator,” The EMBO Journal, vol. 13, no. 17, pp. 4022–4027, 1994.
[102]
R. A. Shroff, R. A. Lockington, and J. M. Kelly, “Analysis of mutations in the creA gene involved in carbon catabolite depression in Aspergillus nidulans,” Canadian Journal of Microbiology, vol. 42, no. 9, pp. 950–959, 1996.
[103]
I. Pócsi, é. Leiter, N.-J. Kwon et al., “Asexual sporulation signalling regulates autolysis of Aspergillus nidulans via modulating the chitinase ChiB production,” Journal of Applied Microbiology, vol. 107, no. 2, pp. 514–523, 2009.
[104]
H. Yamazaki, D. Yamazaki, N. Takaya, M. Takagi, A. Ohta, and H. Horiuchi, “A chitinase gene, chiB, involved in the autolytic process of Aspergillus nidulans,” Current Genetics, vol. 51, no. 2, pp. 89–98, 2007.
[105]
M. Szilágyi, N.-J. Kwon, C. Dorogi, I. Pócsi, J.-H. Yu, and T. Emri, “The extracellular β-1,3-endoglucanase EngA is involved in autolysis of Aspergillus nidulans,” Journal of Applied Microbiology, vol. 109, no. 5, pp. 1498–1508, 2010.
[106]
J. Kamerewerd, I. Zadra, H. Kürnsteiner, and U. Kück, “PcchiB1, encoding a class V chitinase, is affected by PcVelA and PcLaeA, and is responsible for cell wall integrity in Penicillium chrysogenum,” Microbiology, vol. 157, no. 11, pp. 3036–3048, 2011.
[107]
A. Sharon, A. Finkelstein, N. Shlezinger, and I. Hatam, “Fungal apoptosis: function, genes and gene function,” FEMS Microbiology Reviews, vol. 33, no. 5, pp. 833–854, 2009.
[108]
é. Leiter, H. Szappanos, C. Oberparleiter et al., “Antifungal protein PAF severely affects the integrity of the plasma membrane of Aspergillus nidulans and induces an apoptosis-like phenotype,” Antimicrobial Agents and Chemotherapy, vol. 49, no. 6, pp. 2445–2453, 2005.
[109]
F. Marx, U. Binder, é. Leiter, and I. Pócsi, “The Penicillium chrysogenum antifungal protein PAF, a promising tool for the development of new antifungal therapies and fungal cell biology studies,” Cellular and Molecular Life Sciences, vol. 65, no. 3, pp. 445–454, 2008.
[110]
U. Binder, C. Oberparleiter, V. Meyer, and F. Marx, “The antifungal protein PAF interferes with PKC/MPK and cAMP/PKA signalling of Aspergillus nidulans,” Molecular Microbiology, vol. 75, no. 2, pp. 294–307, 2010.
[111]
Y. Q. Zhang, H. Wilkinson, Keller, and N. P. Tsitsigiannis D, “Secondary metabolite gene clusters,” in Handbook of Industrial Mycology, Z. An, Ed., pp. 355–386, 2004.
[112]
J. Yu and N. Keller, “Regulation of secondary metabolism in filamentous fungi,” Annual Review of Phytopathology, vol. 43, pp. 437–458, 2005.
[113]
M. J. Sweeney and A. D. W. Dobson, “Molecular biology of mycotoxin biosynthesis,” FEMS Microbiology Letters, vol. 175, no. 2, pp. 149–163, 1999.
[114]
J. Yu, “Current understanding on aflatoxin biosynthesis and future perspective in reducing aflatoxin contamination,” Toxins, vol. 4, pp. 1024–1057, 2012.
[115]
N. P. Keller and T. H. Adams, “Analysis of a mycotoxin gene cluster in Aspergillus nidulans,” SAAS Bulletin, Biochemistry and Biotechnology, vol. 8, pp. 14–21, 1995.
[116]
N. P. Keller and T. M. Hohn, “Metabolic pathway gene clusters in filamentous fungi,” Fungal Genetics and Biology, vol. 21, no. 1, pp. 17–29, 1997.
[117]
D. W. Brown, J.-H. Yu, H. S. Kelkar et al., “Twenty-five coregulated transcripts define a sterigmatocystin gene cluster in Aspergillus nidulans,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 4, pp. 1418–1422, 1996.
[118]
J. Yu, P. Chang, K. C. Ehrlich et al., “Clustered Pathway Genes in Aflatoxin Biosynthesis,” Applied and Environmental Microbiology, vol. 70, no. 3, pp. 1253–1262, 2004.
[119]
J. Yu, R. A. E. Butchko, M. Fernandes, N. P. Keller, T. J. Leonard, and T. H. Adams, “Conservation of structure and function of the aflatoxin regulatory gene aflR from Aspergillus nidulans and A. flavus,” Current Genetics, vol. 29, no. 6, pp. 549–555, 1996.
[120]
J. K. Hicks, J. Yu, N. P. Keller, and T. H. Adams, “Aspergillus sporulation and mycotoxin production both require inactivation of the FadA Gα protein-dependent signaling pathway,” The EMBO Journal, vol. 16, no. 16, pp. 4916–4923, 1997.
[121]
K. Shimizu, J. K. Hicks, T. Huang, and N. P. Keller, “Pka, Ras and RGS protein interactions regulate activity of aflR, a Zn(II)2Cys6 transcription factor in Aspergillus nidulans,” Genetics, vol. 165, no. 3, pp. 1095–1104, 2003.
[122]
M. Brodhagen and N. P. Keller, “Signalling pathways connecting mycotoxin production and sporulation,” Molecular Plant Pathology, vol. 7, no. 4, pp. 285–301, 2006.
[123]
A. Tag, J. Hicks, G. Garifullina et al., “G-protein signalling mediates differential production of toxic secondary metabolites,” Molecular Microbiology, vol. 38, no. 3, pp. 658–665, 2000.
[124]
L. V. Roze, R. M. Beaudry, N. P. Keller, and J. E. Linz, “Regulation of aflatoxin synthesis by FadA/cAMP/protein kinase A signaling in Aspergillus parasiticus,” Mycopathologia, vol. 158, no. 2, pp. 219–232, 2004.
[125]
D. M. Meyers, G. Obrian, W. L. Du, D. Bhatnagar, and G. A. Payne, “Characterization of aflJ, a gene required for conversion of pathway intermediates to aflatoxin,” Applied and Environmental Microbiology, vol. 64, no. 10, pp. 3713–3717, 1998.
[126]
P.-K. Chang, “The Aspergillus parasiticus protein AFLJ interacts with the aflatoxin pathway-specific regulator aflR,” Molecular Genetics and Genomics, vol. 268, no. 6, pp. 711–719, 2003.
[127]
J. Purschwitz, S. Müller, C. Kastner et al., “Functional and physical interaction of blue- and red-light sensors in Aspergillus nidulans,” Current Biology, vol. 18, no. 4, pp. 255–259, 2008.
[128]
A. Atoui, C. Kastner, C. M. Larey et al., “Cross-talk between light and glucose regulation controls toxin production and morphogenesis in Aspergillus nidulans,” Fungal Genetics and Biology, vol. 47, no. 12, pp. 962–972, 2010.
[129]
N. Kato, W. Brooks, and A. M. Calvo, “The expression of sterigmatocystin and penicillin genes in Aspergillus nidulans is controlled by veA, a gene required for sexual development,” Eukaryotic Cell, vol. 2, no. 6, pp. 1178–1186, 2003.
[130]
J. W. Bok and N. P. Keller, “LaeA, a regulator of secondary metabolism in Aspergillus spp.,” Eukaryotic Cell, vol. 3, no. 2, pp. 527–535, 2004.
[131]
R. M. Perrin, N. D. Fedorova, J. W. Bok et al., “Transcriptional regulation of chemical diversity in Aspergillus fumigatus by LaeA,” PLoS pathogens, vol. 3, no. 4, p. e50, 2007.
[132]
S. P. Kale, L. Milde, M. K. Trapp, J. C. Frisvad, N. P. Keller, and J. W. Bok, “Requirement of LaeA for secondary metabolism and sclerotial production in Aspergillus flavus,” Fungal Genetics and Biology, vol. 45, no. 10, pp. 1422–1429, 2008.
[133]
Y. Reyes-Dominguez, J. W. Bok, H. Berger et al., “Heterochromatic marks are associated with the repression of secondary metabolism clusters in Aspergillus nidulans,” Molecular Microbiology, vol. 76, no. 6, pp. 1376–1386, 2010.
[134]
J. M. Palmer, J. M. Theisen, R. M. Duran, W. S. Grayburn, A. M. Calvo, and N. P. Keller, “Secondary metabolism and development is mediated by LlmF control of VeA subcellular localization in Aspergillus nidulans,” PLoS Genetics, vol. 9, Article ID e1003193, 2013.
[135]
M. I. Shaaban, J. W. Bok, C. Lauer, and N. P. Keller, “Suppressor mutagenesis identifies a velvet complex remediator of Aspergillus nidulans secondary metabolism,” Eukaryotic Cell, vol. 9, no. 12, pp. 1816–1824, 2010.
[136]
？. Bayram and G. H. Braus, “Coordination of secondary metabolism and development in fungi: the velvet family of regulatory proteins,” FEMS Microbiology Reviews, vol. 36, no. 1, pp. 1–24, 2012.
[137]
W. B. Yin, A. W. Reinke, M. Szilágyi et al., “bZIP transcription factors affecting secondary metabolism, sexual development and stress responses in Aspergillus nidulans,” Microbiology, vol. 159, pp. 77–88, 2013.
[138]
P.-K. Chang, J. W. Cary, J. Yu, D. Bhatnagar, and T. E. Cleveland, “The Aspergillus parasiticus polyketide synthase gene pksA, a homolog of Aspergillus nidulans wA, is required for aflatoxin B1 biosynthesis,” Molecular and General Genetics, vol. 248, no. 3, pp. 270–277, 1995.
[139]
K. C. Ehrlich, B. G. Montalbano, and P. J. Cotty, “Sequence comparison of aflR from different Aspergillus species provides evidence for variability in regulation of aflatoxin production,” Fungal Genetics and Biology, vol. 38, no. 1, pp. 63–74, 2003.
