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Original Articles

Genomics of Aspergillus oryzae

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Pages 646-670 | Published online: 22 May 2014

  • 1) Galagan, J. E., Calvo, S. E., Borkovich, K. A., Selker, E. U., Read, N. D., Jaffe, D., FitzHugh, W., Ma, L. J., Smirnov, S., Purcell, S., Rehman, B., Elkins, T., Engels, R., Wang, S., Nielsen, C. B., Butler, J., Endrizzi, M., Qui, D., Ianakiev, P., Bell-Pedersen, D., Nelson, M. A., Werner-Washburne, M., Selitrennikoff, C. P., Kinsey, J. A., Braun, E. L., Zelter, A., Schulte, U., Kothe, G. O., Jedd, G., Mewes, W., Staben, C., Marcotte, E., Greenberg, D., Roy, A., Foley, K., Naylor, J., Stange-Thomann, N., Barrett, R., Gnerre, S., Kamal, M., Kamvysselis, M., Mauceli, E., Bielke, C., Rudd, S., Frishman, D., Krystofova, S., Rasmussen, C., Metzenberg, R. L., Perkins, D. D., Kroken, S., Cogoni, C., Macino, G., Catcheside, D., Li, W., Pratt, R. J., Osmani, S. A., DeSouza, C. P., Glass, L., Orbach, M. J., Berglund, J. A., Voelker, R., Yarden, O., Plamann, M., Seiler, S., Dunlap, J., Radford, A., Aramayo, R., Natvig, D. O., Alex, L. A., Mannhaupt, G., Ebbole, D. J., Freitag, M., Paulsen, I., Sachs, M. S., Lander, E. S., Nusbaum, C., and Birren, B., The genome sequence of the filamentous fungus Neurospora crassa. Nature, 422, 859–868 (2003).
  • 2) Machida, M., Asai, K., Sano, M., Tanaka, T., Kumagai, T., Terai, G., Kusumoto, K.-I., Arima, T., Akita, O., Kashiwagi, Y., Abe, K., Gomi, K., Horiuchi, H., Kitamoto, K., Kobayashi, T., Takeuchi, M., Denning, D. W., Galagan, J. E., Nierman, W. C., Yu, J., Archer, D. B., Bennett, J. W., Bhatnagar, D., Cleveland, T. E., Fedrova, N. D., Gotoh, O., Horikawa, H., Hosoyama, A., Ichinomiya, M., Igarashi, R., Iwashita, K., Juvvadi, P. R., Kato, M., Kato, Y., Kin, T., Kokubun, A., Maeda, H., Maeyama, N., Maruyama, J.-I., Nagasaki, H., Nakajima, T., Oda, K., Okada, K., Paulsen, I., Sakamoto, K., Sawano, T., Takahashi, M., Takase, K., Terabayashi, Y., Wortman, J. R., Yamada, O., Yamagata, Y., Anazawa, H., Hata, Y., Koide, Y., Komori, T., Koyama, Y., Minetoki, T., Suharnan, S., Tanaka, A., Isono, K., Kuhara, S., Ogasawara, N., and Kikuchi, H., Genome sequencing and analysis of Aspergillus oryzae. Nature, 438, 1157–1161 (2005).
  • 3) Machida, M., Progress of Aspergillus oryzae genomics. Adv. Appl. Microbiol., 51, 81–106 (2002).
  • 4) Coulson, A., Sulston, J., Brenner, S., and Karn, J., Toward a physical map of the genome of the nematode Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA, 83, 7826–7830 (1986).
  • 5) Gotoh, O., Homology-based gene structure prediction: simplified matching algorithm using a translated codon (tron) and improved accuracy by allowing for long gaps. Bioinformatics, 16, 190–202 (2000).
  • 6) Asai, K., Itou, K., Ueno, Y., and Yada, T., Recognition of human genes by stochastic parsing. Pac. Symp. Biocomput., 228–239 (1998).
  • 7) Majoros, W. H., Pertea, M., Antonescu, C., and Salzberg, S. L., GlimmerM, Exonomy and Unveil: three ab initio eukaryotic genefinders. Nucleic Acids Res., 31, 3601–3604 (2003).
  • 8) Yu, J., Whitelaw, C. A., Nierman, W. C., Bhatnagar, D., and Cleveland, T. E., Aspergillus flavus expressed sequence tags for identification of genes with putative roles in aflatoxin contamination of crops. FEMS Microbiol. Lett., 237, 333–340 (2004).
  • 9) Florea, L., Hartzell, G., Zhang, Z., Rubin, G. M., and Miller, W., A computer program for aligning a cDNA sequence with a genomic DNA sequence. Genome Res., 8, 967–974 (1998).
  • 10) Tatusov, R. L., Fedorova, N. D., Jackson, J. D., Jacobs, A. R., Kiryutin, B., Koonin, E. V., Krylov, D. M., Mazumder, R., Mekhedov, S. L., Nikolskaya, A. N., Rao, B. S., Smirnov, S., Sverdlov, A. V., Vasudevan, S., Wolf, Y. I., Yin, J. J., and Natale, D. A., The COG database: an updated version includes eukaryotes. BMC Bioinformatics, 4, 41 (2003).
  • 11) Lowe, T. M., and Eddy, S. R., tRNAscan-SE: a program for improved detection of transfer RNA genes in genomic sequence. Nucleic Acids Res., 25, 955–964 (1997).
  • 12) Nierman, W. C., Pain, A., Anderson, M. J., Wortman, J. R., Kim, H. S., Arroyo, J., Berriman, M., Abe, K., Archer, D. B., Bermejo, C., Bennett, J., Bowyer, P., Chen, D., Collins, M., Coulsen, R., Davies, R., Dyer, P. S., Farman, M., Fedorova, N., Fedorova, N., Feldblyum, T. V., Fischer, R., Fosker, N., Fraser, A., García, J. L., García, M. J., Goble, A., Goldman, G. H., Gomi, K., Griffith-Jones, S., Gwilliam, R., Haas, B., Haas, H., Harris, D., Horiuchi, H., Huang, J., Humphray, S., Jiménez, J., Keller, N., Khouri, H., Kitamoto, K., Kobayashi, T., Konzack, S., Kulkarni, R., Kumagai, T., Lafton, A., Latgé, J.-P., Li, W., Lord, A., Lu, C., Majoros, W. H., May, G. S., Miller, B. L., Mohamoud, Y., Molina, M., Monod, M., Mouyna, I., Mulligan, S., Murphy, L., O’Neil, S., Paulsen, I., Peñalva, M. A., Pertea, M., Price, C., Pritchard, B. L., Quail, M. A., Rabbinowitsch, E., Rawlins, N., Rajandream, M.-A., Reichard, U., Renauld, H., Robson, G. D., Rodriguez de Córdoba, S., Rodríguez-Peña, J. M., Ronning, C. M., Rutter, S., Salzberg, S. L., Sanchez, M., Sánchez-Ferrero, J. C., Saunders, D., Seeger, K., Squares, R., Squares, S., Takeuchi, M., Tekaia, F., Turner, G., Vazquez de Aldana, C. R., Weidman, J., White, O., Woodward, J., Yu, J.-H., Fraser, C., Galagan, J. E., Asai, K., Machida, M., Hall, N., Barrell, B., and Denning, D. W., Genomic sequence of the pathogenic and allergenic filamentous fungus, Aspergillus fumigatus. Nature, 438, 1151–1156 (2005).
  • 13) Galagan, J. E., Calvo, S. E., Cuomo, C., Ma, L.-J., Wortman, J. R., Batzoglou, S., Lee, S.-I., Bastürkmen, M., Spevak, C. C., Clutterbuck, J., Kapitonov, V., Jurka, J., Scazzocchio, C., Farman, M., Butler, J., Purcell, S., Harris, S., Braus, G. H., Draht, O., Busch, S., D’Enfert, C., Bouchier, C., Goldman, G. H., Bell-Pedersen, D., Griffiths-Jones, S., Doonan, J. H., Yu, J., Vienken, K., Pain, A., Freitag, M., Selker, E. U., Archer, D. B., Peñalva, M. Á., Oakley, B. R., Momany, M., Tanaka, T., Kumagai, T., Asai, K., Machida, M., Nierman, W. C., Denning, D. W., Caddick, M., Hynes, M., Paoletti, M., Fischer, R., Miller, B., Dyer, P., Sachs, M. S., Osmani, S. A., and Birren, B. W., Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae. Nature, 438, 1105–1115 (2005).
  • 14) Kusumoto, K., Suzuki, S., and Kashiwagi, Y., Telomeric repeat sequence of Aspergillus oryzae consists of dodeca-nucleotides. Appl. Microbiol. Biotechnol., 61, 247–251 (2003).
  • 15) Kitamoto, K., Kimura, K., Gomi, K., and Kumagai, C., Electrophoretic karyotype and gene assignment to chromosomes of Aspergillus oryzae. Biosci. Biotechnol. Biochem., 58, 1467–1470 (1994).
  • 16) Bechert, T., Heck, S., Fleig, U., Diekmann, S., and Hegemann, J. H., All 16 centromere DNAs from Saccharomyces cerevisiae show DNA curvature. Nucleic Acids Res., 27, 1444–1449 (1999).
  • 17) Archer, D. B., and Dyer, P. S., From genomics to post-genomics in Aspergillus. Curr. Opin. Microbiol., 7, 499–504 (2004).
  • 18) Goffeau, A., Barrell, B. G., Bussey, H., Davis, R. W., Dujon, B., Feldmann, H., Galibert, F., Hoheisel, J. D., Jacq, C., Johnston, M., Louis, E. J., Mewes, H. W., Murakami, Y., Philippsen, P., Tettelin, H., and Oliver, S. G., Life with 6000 genes. Science, 274, 546, 563–567 (1996).
  • 19) Goffeau, A., Aert, R., Agostini-Carbone, M. L., Ahmed, A., Aigle, M., Alberghina, L., Albermann, K., Albers, M., Aldea, M., Alexandraki, D., Aljinovic, G., Allen, E., Altmann, R., Alt-Morbe, J., Andre, B., Andrews, S., Ansorge, W., Antoine, G., Anwar, R., Aparicio, A., Araujo, R., Arino, J., Arnold, W., Arroyo, J., Aviles, E., Backes, U., Baclet, M. C., Badcock, K., Bahr, A., Baladron, V., Ballesta, J. P. G., Bankier, A. T., Banrevi, A., Bargues, M., Baron, L., Barreiros, T., Barrell, B. G., Barthe, C., Barton, A. B., Baur, A., Becam, A.-M., Becker, A., Becker, I., Beinhauer, J., Benes, V., Benit, P., Berben, G., Bergantino, E., Bergez, P., Berno, A., Bertani, I., Biteau, N., Bjourson, A. J., Blocker, H., Blugeon, C., Bohn, C., Boles, E., Bolle, P. A., Bolotin-Fukuhara, M., Bordonne, R., Boskovic, J., Bossier, P., Botstein, D., Bou, G., Bowman, S., Boyer, J., Brandt, P., Brandt, T., Brendel, M., Brennan, T., Brinkman, R., Brown, A., Brown, A. J. P., Brown, D., Bruckner, M., Bruschi, C. V., Buhler, J. M., Buitrago, M. J., Bussereau, F., Bussey, H., Camasses, A., Carcano, C., Carignani, G., Carpenter, J., Casamayor, A., Casas, C., Castagnoli, L., Cederberg, H., Cerdan, E., Chalwatzis, N., Chanet, R., Chen, E., Cheret, G., Cherry, J. M., Chillingworth, T., Christiansen, C., Chuat, J.-C., Chung, E., Churcher, C., Churcher, C. M., Clark, M. W., Clemente, M. L., Coblenz, A., Coglievina, M., Coissac, E., Colleaux, L., Connor, R., Contreras, R., Cooper, J., Copsey, T., Coster, F., Coster, R., Couch, J., Crouzet, M., Cziepluch, C., Daignan-Fornier, B., Dal Paro, F., Dang, D. V., D’Angelo, M., Davies, C. J., Davis, K., Davis, R. W., De Antoni, A., Dear, S., Dedman, K., Defoor, E., de Haan, M., Delaveau, Th., Del Bino, S., Delgado, M., Delius, H., Delneri, D., Del Rey, F., Demolder, J., Demolis, N., Devlin, K., de Wergifosse, P., Dietrich, F. S., Ding, H., Dion, C., Dipaolo, T., Doignon, F., Doira, C., Domdey, H., Dover, J., Du, Z., Dubois, E., Dujon, B., Duncan, M., Durand, P., Dusterhoft, A., Dusterhus, S., Eki, T., El Bakkoury, M., Eide, L. G., Entian, K.-D., Eraso, P., Erdmann, D., Erfle, H., Escribano, V., Esteban, M., Fabiani, L., Fabre, F., Fairhead, C., Fartmann, B., Favello, A., Faye, G., Feldmann, H., Fernandes, L., Feroli, F., Feuermann, M., Fiedler, T., Fiers, W., Fleig, U. N., Floth, M., Fobo, G. M., Fortin, N., Foury, F., Francingues-Gaillard, M. C., Franco, L., Fraser, A., Friesen, J. D., Fritz, C., Frontali, L., Fukuhara, H., Fulton, L., Fuller, L. J., Gabel, C., Gaillardin, C., Gaillon, L., Galibert, F., Galisson, F., Galland, P., Gamo, F.-J., Gancedo, C., Garcia-Cantalejo, J. M., Garcia-Gonzalez, M. I., Garcia-Ramirez, J. J., Garcia-Saez, M., Gassenhuber, H., Gatius, M., Gattung, S., Geisel, C., Gent, M. E., Gentles, S., Ghazvini, M., Gigot, D., Gilliquet, V., Glansdorff, N., Gomez-Peris, A., Gonzalez, A., Goulding, S. E., Granotier, C., Greco, T., Grenson, M., Grisanti, P., Grivell, L. A., Grothues, D., Gueldener, U., Guerreiro, P., Guzman, E., Haasemann, M., Habbig, B., Hagiwara, H., Hall, J., Hallsworth, K., Hamberg, K., Hamlin, N., Hand, N. J., Hanemann, V., Hani, J., Hankeln, T., Hansen, M., Harris, D., Harris, D. E., Hartzell, G., Hatat, D., Hattenhorst, U., Hawkins, J., Hebling, U., Hegemann, J., Hein, C., Hennemann, A., Hennessy, K., Herbert, C. J., Hernandez, K., Hernando, Y., Herrero, E., Heumann, K., Heuss-Neitzel, D., Hewitt, N., Hiesel, R., Hilbert, H., Hilger, F., Hillier, L., Hinni, K., Ho, C., Hoenicka, J., Hofmann, B., Hoheisel, J., Hohmann, S., Hollenberg, C. P., Holmstrom, K., Horaitis, O., Horsnell, T. S., Huang, M.-E., Hughes, B., Hunicke-Smith, S., Hunt, S., Hunt, S. E., Huse, K., Hyman, R. W., Iborra, F., Indge, K. J., Iraqui Houssaini, I., Isono, K., Jacq, C., Jacquet, M., Jacquier, A., Jag.... (Remark: This note is truncated in the html because it exceeds the limit of the system (4000 characters per note). The complete text is given in the pdf.)
  • 20) Deckert, G., Warren, P. V., Gaasterland, T., Young, W. G., Lenox, A. L., Graham, D. E., Overbeek, R., Snead, M. A., Keller, M., Aujay, M., Huber, R., Feldmanm, R. A., Short, J. M., Olsen, G. J., and Swanson, R. V., The complete genome of the hyperthermophilic bacterium Aquifex aeolicus. Nature, 392, 353–358 (1998).
  • 21) Lee, D. W., Koh, J. S., Kim, J. H., and Chae, K.-S., Cloning and nucleotide sequence of one of the most highly expressed genes, a pdcA homologue of Aspergillus nidulans, in Aspergillus oryzae. Biotechnol. Lett., 21, 139–142 (1999).
  • 22) Sakaguchi, K., Takagi, M., Horiuchi, H., and Gomi, K., Fungal enzymes used in oriental food and beverage industries. In “Applied Molecular Genetics in Filamentous Fungi,” eds. Kinghorn, J. R., and Turner, G., Blackie Academic and Professional, Glasgow, pp. 54–99 (1992), and references cited therein.
  • 23) Hata, Y., Tsuchiya, K., Kitamoto, K., Gomi, K., Kumagai, C., Tamura, G., and Hara, S., Nucleotide sequence and expression of the glucoamylase-encoding gene (glaA) from Aspergillus oryzae. Gene, 108, 145–150 (1991).
  • 24) Boel, E., Hjort, I., Svensson, B., Norris, F., Norris, K. E., and Fiil, N. P., Glucoamylases G1 and G2 from Aspergillus niger are synthesized from two different but closely related mRNAs. EMBO J., 3, 1097–1102 (1984).
  • 25) Nunberg, J. H., Meade, J. H., Cole, G., Lawyer, F. C., McCabe, P., Schweickart, V., Tal, R., Wittman, V. P., Flatgaard, J. E., and Innis, M. A., Molecular cloning and characterization of the glucoamylase gene of Aspergillus awamori. Mol. Cell. Biol., 4, 2306–2315 (1984).
  • 26) Hata, Y., Ishida, H., Ichikawa, E., Kawato, A., Suginami, K., and Imayasu, S., Nucleotide sequence of an alternative glucoamylase-encoding gene (glaB) expressed in solid-state culture of Aspergillus oryzae. Gene, 207, 127–134 (1998).
  • 27) Minetoki, T., Gomi, K., Kitamoto, K., Kumagai, C., and Tamura, G., Nucleotide sequence and expression of α-glucosidase-encoding gene (agdA) from Aspergillus oryzae. Biosci. Biotechnol. Biochem., 59, 1516–1521 (1995).
  • 28) Gomi, K., Akeno, T., Minetoki, T., Ozeki, K., Kumagai, C., Okazaki, N., and Iimura, Y., Molecular cloning and characterization of a transcriptional activator gene, amyR, involved in the amylolytic gene expression in Aspergillus oryzae. Biosci. Biotechnol. Biochem., 64, 816–827 (2000).
  • 29) Kato, N., Suyama, S., Shirokane, M., Kato, M., Kobayashi, T., and Tsukagoshi, N., Novel α-glucosidase from Aspergillus nidulans with strong transglycosylation activity. Appl. Environ. Microbiol., 68, 1250–1256 (2002).
  • 30) de Vries, R. P., and Visser, J., Aspergillus enzymes involved in degradation of plant cell wall polysaccharides. Microbiol. Mol. Biol. Rev., 65, 497–522 (2001).
  • 31) de Vries, R. P., Jansen, J., Aguilar, G., Parenicova, L., Joosten, V., Wulfert, F., Benen, J. A., and Visser, J., Expression profiling of pectinolytic genes from Aspergillus niger. FEBS Lett., 530, 41–47 (2002).
  • 32) Linder, M., and Teeri, T. T., The roles and function of cellulose-binding domains. J. Biotechonol., 57, 15–28 (1997).
  • 33) Svensson, B., Pedersen, T. G., Svendsen, I., Sakai, T., and Ottesen, M., Characterization of two forms of glucoamylase from Aspergillus niger. Carlsberg Res. Commun., 47, 55–69 (1982).
  • 34) Kaneko, A., Sudo, S., Sakamoto, Y., Tamura, G., Ishikawa, T., and Ohba, T., Molecular-cloning and determination of the nucleotide-sequence of a gene encoding an acid-stable α-amylase from Aspergillus kawachii. J. Ferment. Bioeng., 81, 292–298 (1996).
  • 35) Geiser, D. M., Pitt, J. I., and Taylor, J. W., Cryptic speciation and recombination in the aflatoxin producing fungus Aspergillus flavus. Proc. Natl. Acad. Sci. USA, 95, 388–393 (1998).
  • 36) Barret, A. J., Proteolytic enzymes: serine and cysteine peptidases. Methods Enzymol., 244, 1–765 (1994).
  • 37) Barret, A. J., Proteolytic enzymes: aspartic and metallo peptidases. Methods Enzymol., 248, 1–873 (1995).
  • 38) Gomi, K., Arikawa, K., Kamiya, N., Kitamoto, K., and Kumagai, C., Cloning and nucleotide sequence of the acid protease-encoding gene (pepA) from Aspergillus oryzae. Biosci. Biotechnol. Biochem., 57, 1096–1100 (1993).
  • 39) Kunihiro, S., Kawanishi, Y., Sano, Y., Abe, K., Matsuura, Y., Tateno, Y., Gojobori, T., Yamagata, Y., Abe, K., and Machida, M., A polymerase chain reaction-based method for cloning novel members of a gene family using a combination of degenerate and inhibitory primers. Gene, 289, 177–184 (2002).
  • 40) Kamitori, S., Ohtaki, A., Ino, H., and Takeuchi, M., Crystal structures of Aspergillus oryzae aspartic proteinase and its complex with an inhibitor pepstatin at 1.9 A resolution. J. Mol. Biol., 326, 1503–1511 (2003).
  • 41) Blinkovsky, A. M., Byun, T., Brown, K. M., and Gelightly, E. J., Purification, characterization, and heterologous expression in Fusarium venenatum of a novel serine carboxypeptidase from Aspergillus oryzae. Appl. Environ. Microbiol., 65, 3298–3303 (1999).
  • 42) Barton, G. J., and Sternberg, M. J., A strategy for the rapid multiple alignment of protein sequences: confidence levels from tertiary structure comparisons. J. Mol. Biol., 198, 327–337 (1987).
  • 43) Todd, R. B., and Andrianopoulos, A., Evolution of a fungal regulatory gene family: the Zn(II)2Cys6 binuclear cluster DNA binding motif. Fungal Genet. Biol., 21, 388–405 (1997).
  • 44) Bhat, J. P., and Murthy, T. V. S., Transcriptional control of the GAL/MEL regulon of yeast Saccharomyces cerevisiae: mechanism of galactose-mediated signal transduction. Mol. Microbiol., 40, 1059–1066 (2001).
  • 45) Borkovich, K. A., Alex, L. A., Yarden, O., Freitag, M., Turner, G. E., Read, N. D., Seiler, S., Bell-Pedersen, D., Paietta, J., Plesofsky, N., Plamann, M., Goodrich-Tanrikulu, M., Schulte, U., Mannhaupt, G., Nargang, F. E., Radford, A., Selitrennikoff, C., Galagan, J. E., Dunlap, J. C., Loros, J. J., Catcheside, D., Inoue, H., Aramayo, R., Polymenis, M., Selker, E. U., Sachs, M. S., Marzluf, G. A., Paulsen, I., Davis, R., Ebbole, D. J., Zelter, A., Kalkman, E. R., O’Rourke, R., Bowring, F., Yeadon, J., Ishii, C., Suzuki, K., Sakai, W., and Pratt, R., Lessons from the genome sequence of Neurospora crassa: tracing the path from genomic blueprint to multicellular organism. Microbiol. Mol. Biol. Rev., 68, 1–108 (2004).
  • 46) Hellauer, K., Akache, B., MacPherson, S., Sirard, E., and Turcotte, B., Zinc cluster protein Rdr1p is a transcriptional repressor of the PDR5 gene encoding a multidrug transporter. J. Biol. Chem., 277, 17671–17676 (2002).
  • 47) Suarez, T., de Queiroz, M. V., Oestreicher, N., and Scazzocchio, C., The sequence and binding specificity of UaY, the specific regulator of the purine utilization pathway in Aspergillus nidulans, suggest an evolutionary relationship with the PPR1 protein of Saccharomyces cerevisiae. EMBO J., 14, 1453–1467 (1995).
  • 48) Burger, G., Strauss, J., Scazzocchio, C., and Lang, B. F., nirA, the pathway-specific regulatory gene of nitrate assimilation in Aspergillus nidulans, encodes a putative GAL4-type zinc finger protein and contains four introns in highly conserved regions. Mol. Cell. Biol., 11, 5746–5755 (1991).
  • 49) Masloff, S., Jacobsen, S., Poggeler, S., and Kuck, U., Functional analysis of the C6 zinc finger gene pro1 involved in fungal sexual development. Fungal Genet. Biol., 36, 107–116 (2002).
  • 50) Vienken, K., Scherer, M., and Fischer, R., The Zn(II)2Cys6 putative Aspergillus nidulans transcription factor RosA (repressor of sexual development) inhibits sexual development under low-carbon conditions and in submerged culture. Genetics, 169, 619–630 (2005).
  • 51) Petersen, K. L., Lehmbeck, J., and Christensen, J., A new transcriptional activator for amylase genes in Aspergillus. Mol. Gen. Genet., 262, 668–676 (1999).
  • 52) Tani, S., Katsuyama, Y., Hayashi, T., Suzuki, H., Kato, M., Gomi, K., Kobayashi, T., and Tsukagoshi, N., Characterization of the amyR gene encoding a transcriptional activator for the amylase genes in Aspergillus nidulans. Curr. Genet., 39, 10–15 (2001).
  • 53) Kato, N., Murakoshi, Y., Kato, M., Kobayashi, T., and Tsukagoshi, N., Isomaltose formed by α-glucosidases triggers amylase induction in Aspergillus nidulans. Curr. Genet., 42, 43–50 (2002).
  • 54) Chow, T. H., Sollitti, P., and Marmur, J., Structure of multigene family of MAL loci in Saccharomyces. Mol. Gen. Genet., 217, 60–69 (1989).
  • 55) Yu, J., Chang, P., Bhatnagar, D., and Cleaveland, T. E., Cloning of a sugar utilization cluster in Aspergillus parasiticus. Biochim. Biophys. Acta, 1493, 211–214 (2000).
  • 56) Marui, J., Tanaka, A., Mimura, S., de Graaff, L. H., Visser, J., Kitamoto, N., Kato, M., Kobayashi, T., and Tsukagoshi, N., A transcriptional activator, AoXlnR, controls the expression of genes encoding xylanolytic enzymes in Aspergillus oryzae. Fungal Genet. Biol., 35, 157–169 (2002).
  • 57) van Peij, N. N., Visser, J., and de Graaff, L. H., Isolation and analysis of XlnR, encoding a transcriptional activator co-ordinating xylanolytic expression in A. niger. Mol. Microbiol., 27, 131–142 (1998).
  • 58) van Peij, N. N., Gielkens, M. M., de Vries, R. P., Visser, J., and de Graaff, L. H., The transcriptional activator XlnR regulates both xylanolytic and endoglucanase gene expression in Aspergillus niger. Appl. Environ. Microbiol., 64, 3615–3619 (1998).
  • 59) Marui, J., Kitamoto, N., Kato, M., Kobayashi, T., and Tsukagoshi, N., Transcriptional activator, AoXlnR, mediates cellulose-inductive expression of the xylanolytic and cellulolytic genes in Aspergillus oryzae. FEBS Lett., 528, 279–282 (2002).
  • 60) Woloshuk, C. P., Fouts, K. R., Brewer, J. F., Bhatnagar, D., Cleaveland, T. E., and Payne, C. A., Molecular characterization of aflR, a regulatory locus for aflatoxin biosynthesis. Appl. Environ. Microbiol., 60, 2408–2414 (1994).
  • 61) Yu, J. H., Butchko, R. A., Fernandes, M., Keller, N. P., Leonard, T. J., and Adams, T. H., Conservation of structure and function of the aflatoxin regulatory gene aflR from Aspergillus nidulans and A. flavus. Curr. Genet., 29, 549–555 (1996).
  • 62) Watson, A. J., Fuller, L. J., Jeenes, D. J., and Archer, D. B., Homologs of aflatoxin biosynthesis genes and sequence of aflR in Aspergillus oryzae and Aspergillus sojae. Appl. Environ. Microbiol., 65, 307–310 (1998).
  • 63) Kusumoto, K., Yabe, K., Nogata, Y., and Ohta, H., Transcript of a homolog of aflR, a regulatory gene for aflatoxin synthesis in Aspergillus parasiticus, was not detected in Aspergillus oryzae strains. FEMS Microbiol. Lett., 169, 303–307 (1998).
  • 64) Liu, B. H., and Chu, F. S., Regulation of aflR and its product, AflR, associated with aflatoxin biosynthesis. Appl. Environ. Microbiol., 64, 3718–3723 (1998).
  • 65) Takahashi, T., Chang, P. K., Matsushima, K., Yu, J., Abe, K., Bhatnagar, D., Cleaveland, T. E., and Koyama, Y., Nonfunctionality of Aspergillus sojae aflR in a strain of Aspergillus parasiticus with a disrupted aflR gene. Appl. Environ. Microbiol., 68, 3737–3743 (2002).
  • 66) Wang, X. W., Hynes, M. J., and Davis, M. A., Structural and functional analysis of the amdR regulatory gene of Aspergillus oryzae. Gene, 122, 147–154 (1992).
  • 67) Todd, R. B., Murphy, R. L., Martin, H. M., Sharp, J. A., Davis, M. A., Katz, M. E., and Hynes, M. J., The acetate regulatory gene facB of Aspergillus nidulans encodes a Zn(II)2Cys6 transcriptional activator. Mol. Gen. Genet., 254, 495–504 (1997).
  • 68) Small, A. J., Todd, R. B., Zanker, M. C., Delimitrou, S., Hynes, M. J., and Davis, M. A., Functional analysis of TamA, a coactivator of nitrogen-regulated gene expression in Aspergillus nidulans. Mol. Genet. Genomics, 265, 636–646 (2001).
  • 69) Beri, R. K., Whittington, H., Roberts, C. F., and Hawkings, A. R., Isolation and characterization of the positively acting regulatory gene QUTA from Aspergillus nidulans. Nucleic Acids Res., 15, 7991–8001 (1987).
  • 70) Cazelle, B., Pokorska, A., Hull, E., Green, P. M., Stanway, G., and Scazzochio, C., Sequence, exon-intron organization, transcription and mutational analysis of prnA, the gene encoding the transcriptional activator of the prn gene cluster in Aspergillus nidulans. Mol. Microbiol., 28, 355–370 (1998).
  • 71) Li, D., and Kolattukudy, P. E., Cloning of cutinase transcription factor 1, a transactivating protein containing Cys6Zn2 binuclear cluster DNA-binding motif. J. Biol. Chem., 272, 12462–12467 (1997).
  • 72) Li, D., Sirakova, T., Rogers, L., Ettinger, W. F., and Kolattukudy, P. E., Regulation of constitutively expressed and induced cutinase genes by different zinc finger transcription factors in Fusarium solani f. sp. pisi (Nectria haematococca). J. Biol. Chem., 277, 7905–7912 (2002).
  • 73) Felenbok, B., Sequeval, D., Mathiu, M., Sibley, S., Gwynne, D. I., and Davies, R. W., The ethanol regulon in Aspergillus nidulans: characterization and sequence of the positive regulatory gene alcR. Gene, 73, 385–396 (1988).
  • 74) Empel, J., Sitkiewicz, I., Andrukiewicz, A., Lasocki, K., Borsuk, P., and Weglenski, P., arcA, the regulatory gene for the arginine catabolic pathway in Aspergillus nidulans. Mol. Genet. Genomics, 266, 591–597 (2001).
  • 75) Yamada, O., Lee, B. R., Gomi, K., and Iimura, Y., Cloning and functional analysis of the Aspergillus oryzae conidiation regulator gene brlA by its disruption and misscheduled expression. J. Biosci. Bioeng., 87, 424–429 (1999).
  • 76) Felenbok, B., and Kelly, J. M., Regulation of carbon metabolism in mycelial fungi. In “The Mycota III, Biochemistry and Molecular Biology,” eds. Brambl, R., and Marzluf, G. A., Springer-Verlag, Berlin, pp. 369–380 (1996).
  • 77) Timberlake, W. E., Temporal and spatial controls of Aspergillus development. Curr. Opin. Genet. Dev., 1, 351–357 (1991).
  • 78) Arst, H. N., and Peñalva, M. A., pH regulation in Aspergillus and parallels with higher eukaryotic regulatory systems. Trends Genet., 19, 224–231 (2003).
  • 79) Lints, R., Davis, M. A., and Hynes, M. J., The positively acting amdA gene of Aspergillus nidulans encodes a protein with two C2H2 zinc-finger motifs. Mol. Microbiol., 15, 965–975 (1995).
  • 80) Murphy, R. L., Andrianopoulos, A., Davis, M. A., and Hynes, M. J., Identification of amdX, a new Cys-2-His-2 (C2H2) zinc-finger gene involved in the regulation of the amdS gene of Aspergillus nidulans. Mol. Microbiol., 23, 591–602 (1997).
  • 81) Saloheimo, A., Aro, N., Ilmén, M., and Penttilã, M., Isolation of the ace1 gene encoding a Cys(2)-His(2) transcription factor involved in regulation of activity of the cellulase promoter cbh1 of Trichoderma reesei. J. Biol. Chem., 275, 5817–5825 (2000).
  • 82) Adams, T. H., Wieser, J. K., and Yu, J. H., Asexual sporulation in Aspergillus nidulans. Microbiol. Mol. Biol. Rev., 62, 35–54 (1998).
  • 83) Christensen, T., Hynes, M. J., and Davis, M. A., Role of the regulatory gene areA of Aspergillus oryzae in nitrogen metabolism. Appl. Environ. Microbiol., 64, 3232–3237 (1998).
  • 84) Arst, H. N., Tollervey, D., and Caddick, M. X., A translocation associated, loss-of-function mutation in the nitrogen metabolite repression regulatory gene of Aspergillus nidulans can revert intracistronically. Mol. Gen. Genet., 215, 364–367 (1989).
  • 85) Haas, H., Zadra, I., Stoffler, G., and Angermay, K., The Aspergillus nidulans GATA factor SREA is involved in regulation of siderophore biosynthesis and control of iron uptake. J. Biol. Chem., 274, 4613–4619 (1999).
  • 86) Han, K. H., Han, K. Y., Yu, J. H., Chae, K. S., Jahng, K. Y., and Han, D. M., The nsdD gene encodes a putative GATA-type transcription factor necessary for sexual development of Aspergillus nidulans. Mol. Microbiol., 41, 299–309 (2001).
  • 87) Ballario, P., Vuttorioso, P., Magrelli, A., Talora, C., Cabibbo, A., and Macino, G., White collar-1, a central regulator of blue light responses in Neurospora, is a zinc finger protein. EMBO J., 15, 1650–1657 (1996).
  • 88) Li, D., and Kolattukudy, P. E., Cloning and expression of cDNA encoding a protein that binds a palindromic promoter element essential for induction of fungal cutinase by plant cutin. J. Biol. Chem., 270, 11753–11756 (1995).
  • 89) Murre, C., McCaw, P. S., and Baltimore, D., A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell, 56, 777–783 (1989).
  • 90) Caruso, M. L., Litzka, O., Martic, G., Lottspeicch, F., and Brakhage, A. A., Novel basic-region helix-loop-helix transcription factor (AnBH1) of Aspergillus nidulans counteracts the CCAAT-binding complex AnCF in the promoter of a penicillin biosynthesis gene. J. Mol. Biol., 323, 425–439 (2002).
  • 91) Tüncher, A., Reinke, H., Martic, G., Caruso, M. L., and Brakhage, A. A., A basic-region helix-loop-helix protein-encoding gene (devR) involved in the development of Aspergillus nidulans. Mol. Microbiol., 52, 227–241 (2004).
  • 92) Vinson, C. R., Sigler, P. B., and McKnight, S. L., Scissors-grip model for DNA recognition by a family of leucine zipper proteins. Science, 246, 911–916 (1989).
  • 93) Tanaka, A., Kato, M., Nagase, T., Kobayashi, T., and Tsukagoshi, N., Isolation of genes encoding novel transcription factors which interact with the Hap complex from Aspergillus species. Biochim. Biophys. Acta, 1576, 176–182 (2002).
  • 94) Natorff, R., Sienko, M., Brzywczy, J., and Paszewski, A., The Aspergillus nidulans metR gene encodes a bZIP protein which activates transcription of sulphur metabolism genes. Mol. Microbiol., 49, 1081–1094 (2003).
  • 95) Furukawa, K., Katsuno, Y., Urao, T., Yabe, T., Yamada-Okabe, T., Yamada-Okabe, H., Yamagata, Y., Abe, K., and Nakajima, T., Isolation and functional analysis of a gene, tcsB, encoding a transmembrane hybrid-type histidine kinase from Aspergillus nidulans. Appl. Environ. Microbiol., 68, 5304–5310 (2002).
  • 96) Virginia, M., Appleyard, C. L., McPheat, W. L., and Stark, M. J., A novel ‘two-component’ protein containing histidine kinase and response regulator domains required for sporulation in Aspergillus nidulans. Curr. Genet., 37, 364–372 (2000).
  • 97) Pott, G. B., Miller, T. K., Bartlett, J. A., Palas, J. S., and Selitrennikoff, C. P., The isolation of FOS-1, a gene encoding a putative two-component histidine kinase from Aspergillus fumigatus. Fungal Genet. Biol., 31, 55–67 (2000).
  • 98) Catlett, N. L., Yoder, O. C., and Turgeon, B. G., Whole-genome analysis of two-component signal transduction genes in fungal pathogens. Eukaryotic Cell, 2, 1151–1161 (2003).
  • 99) Buck, V., Quinn, J., Pino, T. S., Martin, H., Saldanha, J., Makino, K., Morgan, B. A., and Millar, J. B. A., Peroxide sensors for the fission yeast stress-activated mitogen-activated protein kinase pathway. Mol. Biol. Cell, 12, 407–419 (2001).
  • 100) Aoyama, K., Aiba, H., and Mizuno, T., Genetic analysis of the His-to-Asp phosphorelay implicated in mitotic cell cycle control: involvement of histidine-kinase genes of Shizosaccharomyces pombe. Biosci. Biotechnol. Biochem., 65, 2347–2352 (2001).
  • 101) Nakamichi, N., Yamada, H., Aoyama, K., Ohmiya, R., Aiba, H., and Mizuno, T., His-to-Asp phosphorelay circuitry for regulation of sexual development in Shizosaccharomyces pombe. Biosci. Biotechnol. Biochem., 66, 2663–2672 (2002).
  • 102) Alex, L. A., Borkovich, K. A., and Simon, M. I., Hyphal development in Neurospora crassa: involvement of a two-component histidine kinase. Proc. Natl. Acad. Sci. USA, 93, 3416–3421 (1996).
  • 103) Hohmann, S., Osmotic stress signalling and osmoadaptation in yeasts. Microbiol. Mol. Biol. Rev., 66, 300–372 (2002).
  • 104) Keyse, S. M., Protein phosphatases and the regulation of mitogen activated protein kinase signalling. Curr. Opin. Cell Biol., 12, 186–192 (2000).
  • 105) Elion, E. A., Pheromone response, mating and cell biology. Curr. Opin. Microbiol., 3, 573–581 (2000).
  • 106) Gustin, M. C., Albertyn, J., Alexander, M., and Davenport, K., MAP kinase pathways in the yeast Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rev., 62, 1264–1300 (1998).
  • 107) Herskowitz, I., MAP kinase pathways in yeast: for mating and more. Cell, 80, 187–197 (1995).
  • 108) Posas, F., Takekawa, M., and Saito, H., Signal transduction by MAP kinase cascades in budding yeast. Curr. Opin. Microbiol., 1, 175–182 (1998).
  • 109) Han, K. H., and Prade, R. A., Osmotic stress-coupled maintenance of polar growth in Aspergillus nidulans. Mol. Microbiol., 43, 1065–1078 (2002).
  • 110) Kawasaki, L., Sanchez, O., Shiozaki, K., and Aguirre, J., SakA MAP kinase is involved in stress signal transduction, sexual development and spore viability in Aspergillus nidulans. Mol. Microbiol., 45, 1153–1163 (2002).
  • 111) Xue, T., Nguyen, C. K., Romans, A., and May, G. S., A mitogen-activated protein kinase that senses nitrogen regulates conidial germination and growth in Aspergillus fumigatus. Eukaryotic Cell, 3, 557–560 (2004).
  • 112) Bussink, H., and Osmani, S. A., A mitogen-activated protein kinase (MPKA) is involved in polarized growth in the filamentous fungus, Aspergillus nidulans. FEMS Microbiol. Lett., 173, 117–125 (1999).
  • 113) Mizutani, O., Nojima, A., Yamamoto, M., Furukawa, K., Fujioka, T., Yamagata, Y., Abe, K., and Nakajima, T., Disordered cell integrity signalling by disruption of kexB gene in Aspergillus oryzae. Eukaryotic Cell, 3, 1036–1048 (2004).
  • 114) Furukawa, K., Hoshi, Y., Maeda, T., Nakajima, T., and Abe, K., Aspergillus nidulansHOG pathway is activated only by two-component signaling pathway in response to osmotic stress. Mol. Microbiol., 56, 1246–1261 (2005).
  • 115) Wei, H., Requena, N., and Fischer, R., The MAPKK kinase SteC regulates conidiophore morphology and is essential for heterokaryon formation and sexual development in the homothallic fungus Aspergillus nidulans. Mol. Microbiol., 47, 1577–1588 (2003).
  • 116) Smits, G. J., Kapteyn, J. C., van den Ende, H., and Klis, F. M., Cell wall dynamics in yeast. Curr. Opin. Microbiol., 2, 348–352 (1999).
  • 117) Klis, F. M., Review: cell wall assembly in yeast. Yeast, 10, 851–869 (1994).
  • 118) Kapteyn, J. C., van den Ende, H., and Klis, F. M., The contribution of cell wall proteins to the organization of the yeast cell wall. Biochim. Biophys. Acta, 1426, 373–383 (1999).
  • 119) Fontaine, T., Simenel, C., Dubreucq, G., Adam, O., Delepierre, M., Lemoine, J., Vorgias, C. E., Diaquin, M., and Latge, J. P., Molecular organization of the alkali-insoluble fraction of Aspergillus fumigatus cell wall. J. Biol. Chem., 275, 27594–27607 (2000).
  • 120) Heinisch, J. J., Lorberg, A., Schmitz, H. P., and Jacoby, J. J., The protein kinase C-mediated MAP kinase pathway involved in the maintenance of cellular integrity in Saccharomyces cerevisiae. Mol. Microbiol., 32, 671–680 (1999).
  • 121) Verna, J., Lodder, A., Lee, K., Vagts, A., and Ballester, R., A family of genes required for maintenance of cell wall integrity and for the stress response in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA, 94, 13804–13809 (1997).
  • 122) Lodder, A. L., Lee, T. K., and Ballester, R., Characterization of the Wsc1 protein, a putative receptor in the stress response of Saccharomyces cerevisiae. Genetics, 152, 1487–1499 (1999).
  • 123) Rajavel, M., Philip, B., Buehrer, B. M., Errede, B., and Levin, D. E., Mid2 is a putative sensor for cell integrity signalling in Saccharomyces cerevisiae. Mol. Cell. Biol., 19, 3969–3976 (1999).
  • 124) Levin, D. E., Fields, F. O., Kunisawa, R., Bishop, J. M., and Thorner, J., A candidate protein kinase C gene, PKC1, is required for the S. cerevisiae cell cycle. Cell, 62, 213–224 (1990).
  • 125) Philip, B., and Levin, D. E., Wsc1 and Mid2 are cell surface sensors for cell wall integrity signalling that act through Rom2, a guanine nucleotide exchange factor for Rho1. Mol. Cell. Biol., 21, 271–280 (2001).
  • 126) Schmidt, A., Bickle, M., Beck, T., and Hall, M. N., The yeast phosphatidylinositol kinase homolog TOR2 activates RHO1 and RHO2 via the exchange factor ROM2. Cell, 88, 531–542 (1997).
  • 127) Kamada, Y., Qadota, H., Python, C. P., Anraku, Y., Ohya, Y., and Levin, D. E., Activation of yeast protein kinase C by Rho1 GTPase. J. Biol. Chem., 271, 9193–9196 (1996).
  • 128) Lee, K. S., and Levin, D. E., Dominant mutations in a gene encoding a putative protein kinase (BCK1) bypass the requirement for a Saccharomyces cerevisiae protein kinase C homolog. Mol. Cell. Biol., 12, 172–182 (1992).
  • 129) Irie, K., Takase, M., Lee, K. S., Levin, D. E., Araki, H., Matsumoto, K., and Oshima, Y., MKK1 and MKK2, which encode Saccharomyces cerevisiae mitogen-activated protein kinase–kinase homologs, function in the pathway mediated by protein kinase C. Mol. Cell. Biol., 13, 3076–3083 (1993).
  • 130) Martin, H., Arroyo, J., Sanchez, M., Molina, M., and Nombela, C., Activity of the yeast MAP kinase homologue Slt2 is critically required for cell integrity at 37 °C. Mol. Gen. Genet., 241, 177–184 (1993).
  • 131) Jung, U. S., and Levin, D. E., Genome-wide analysis of gene expression regulated by the yeast cell wall integrity signalling pathway. Mol. Microbiol., 34, 1049–1057 (1999).
  • 132) Roelants, F. M., Torrance, P. D., Bezman, N., and Thorner, J., Pkh1 and Pkh2 differentially phosphorylate and activate ypk1 and ykr2 and define protein kinase modules required for maintenance of cell wall integrity. Mol. Biol. Cell, 13, 3005–3028 (2002).
  • 133) Zhao, C., Jung, U. S., Garrett-Engele, P., Roe, T., Cyert, M. S., and Levin, D. E., Temperature-induced expression of yeast FKS2 is under the dual control of protein kinase C and calcineurin. Mol. Cell. Biol., 18, 1013–1022 (1998).
  • 134) Stathopoulos, A. M., and Cyert, M. S., Calcineurin acts through the CRZ1/TCN1-encoded transcription factor to regulate gene expression in yeast. Genes Dev., 11, 3432–3444 (1997).
  • 135) Xu, J. R., Staiger, C. J., and Hamer, J. E., Inactivation of the mitogen-activated protein kinase Mps1 from the rice blast fungus prevents penetration of host cells but allows activation of plant defense responses. Proc. Natl. Acad. Sci. USA, 95, 12713–12718 (1998).
  • 136) Kitamoto, K., Gomi, K., Goto, K., and Hara, S., Genetic transfer applied to traditional sake brewing. Biotechnol. Genet. Eng. Rev., 9, 89–125 (1991).
  • 137) Christensen, T., Wøldike, H., Boel, E., Mortensen, S. B., Hjortshøj, K., Thim, L., and Hansen, M. T., High level expression of recombinant genes in Aspergillus oryzae. Biotechnology, 6, 1419–1422 (1988).
  • 138) Kitamoto, K., Molecular biology of the Koji molds. Adv. Appl. Microbiol., 51, 129–153 (2001).
  • 139) Conesa, A., Punt, P. J., van Luijk, N., and van den Hondel, C. A., The secretion pathway in filamentous fungi: a biotechnological view. Fungal Genet. Biol., 33, 155–171 (2001).
  • 140) Travers, K. J., Patil, C. K., Wodicka, L., Lockhart, D. J., Weissman, J. S., and Walter, P., Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation. Cell, 101, 249–258 (2000).
  • 141) Gerst, J. E., SNARE regulators: matchmakers and matchbreakers. Biochim. Biophy. Acta, 1641, 99–110 (2003).
  • 142) Pelham, H. R. B., SNAREs and the specificity of membrane fusion. Trends Cell Biol., 11, 99–101 (2001).
  • 143) Gupta, G. D., and Heath, I. B., Predicting the distribution and functions of SNAREs and related proteins in fungi. Fungal Genet. Biol., 36, 1–21 (2002).
  • 144) Wang, H., and Ward, M., Molecular characterization of a PDI-related gene prpA in Aspergillus niger var. awamori. Curr. Genet., 37, 57–64 (2000).
  • 145) Gupta, G. D., Free, S. J., Levina, N. N., Keranen, S., and Heath, I. B., Two divergent plasma membrane syntaxin-like SNAREs, nsyn1 and nsyn2, contribute to hyphal tip growth and other developmental processes in Neurospora crassa. Fungal Genet. Biol., 40, 271–286 (2003).
  • 146) Jantti, J., Aalto, M. K., Oyen, M., Sundqvist, L., Keranen, S., and Ronne, H., Characterization of temperature sensitive mutations in the yeast syntaxin homologues Sso1p and Sso2p, and evidence for a distinct function for Sso1p in sporulation. J. Cell Sci., 115, 409–420 (2002).
  • 147) Neiman, A. M., Katz, L., and Brennwald, P. J., Identification of domains required for developmentally regulated SNARE function in Saccharomyces cerevisiae. Genetics, 155, 1643–1655 (2000).
  • 148) Archer, D. B., and Peberdy, J. F., The molecular biology of secreted enzyme production by fungi. Crit. Rev. Biotechnol., 17, 273–306 (1997).

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