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2. Effective lead selection for improved protein production in Aspergillus niger based on integrated genomics

Author

Jacobs, Denise I., Olsthoorn, Maurien M.A., Maillet, Isabelle, Akeroyd, Michiel, Breestraat, Stefaan, Donkers, Serge, van der Hoeven, Rob A.M., van den Hondel, Cees A.M.J.J., Kooistra, Rolf, Lapointe, Thomas, Menke, Hildegard, Meulenberg, Rogier, Misset, Marijke, Müller, Wally H., van Peij, Noël N.M.E., Ram, Arthur, Rodriguez, Sabrina, Roelofs, Marc S., Roubos, Johannes A., van Tilborg, Marcel W.E.M., Verkleij, Arie J., Pel, Herman J., Stam, Hein, and Sagt, Cees M.J.

Published
2009
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3. Comparative genomics of citric-acid-producing Aspergillus niger ATCC 1015 versus enzyme-producing CBS 513.88

Author

Universidad de Sevilla. Departamento de Genética, Andersen, Mikael R., Salazar, Margarita P., Schaap, Peter J., Vondervoort, Peter J.I. van de, Culley, David, Thykaer, Jette, Frisvad, Jens C., Nielsen, Kristian F., Albang, Richard, Albermann, Kaj, Berka, Randy M., Braus, Gerhard H., Braus-Stromeyer, Susanna A., Corrochano Peláez, Luis María, Dai, Ziyu, Dijck, Piet W.M. van, Hofmann, Gerald, Lasure, Linda L., Magnuson, Jon K., Menke, Hildegard, Meijer, Martin, Meijer, Susan L., Nielsen, Jakob B., Nielsen, Michael L., Ooyen, Albert J.J. van, Pel, Herman J., Poulsen, Lars, Samson, Rob A., Stam, Hein, Tsang, Adrian, Brink, Johannes M. van den, Atkins, Alex, Aerts, Andrea, Shapiro, Harris, Pangilinan, Jasmyn, Salamov, Asaf, Yigong Lou, Lindquist, Erika, Lucas, Susan M., Grimwood, Jane, Grigoriev, Igor V., Kubicek, Christian P., Martinez, Diego, Peij, Noe¨l N.M.E. van, Roubos, Johannes A., Nielsen, Jens, Baker, Scott E., Universidad de Sevilla. Departamento de Genética, Andersen, Mikael R., Salazar, Margarita P., Schaap, Peter J., Vondervoort, Peter J.I. van de, Culley, David, Thykaer, Jette, Frisvad, Jens C., Nielsen, Kristian F., Albang, Richard, Albermann, Kaj, Berka, Randy M., Braus, Gerhard H., Braus-Stromeyer, Susanna A., Corrochano Peláez, Luis María, Dai, Ziyu, Dijck, Piet W.M. van, Hofmann, Gerald, Lasure, Linda L., Magnuson, Jon K., Menke, Hildegard, Meijer, Martin, Meijer, Susan L., Nielsen, Jakob B., Nielsen, Michael L., Ooyen, Albert J.J. van, Pel, Herman J., Poulsen, Lars, Samson, Rob A., Stam, Hein, Tsang, Adrian, Brink, Johannes M. van den, Atkins, Alex, Aerts, Andrea, Shapiro, Harris, Pangilinan, Jasmyn, Salamov, Asaf, Yigong Lou, Lindquist, Erika, Lucas, Susan M., Grimwood, Jane, Grigoriev, Igor V., Kubicek, Christian P., Martinez, Diego, Peij, Noe¨l N.M.E. van, Roubos, Johannes A., Nielsen, Jens, and Baker, Scott E.

Abstract

The filamentous fungus Aspergillus niger exhibits great diversity in its phenotype. It is found globally, both as marine and terrestrial strains, produces both organic acids and hydrolytic enzymes in high amounts, and some isolates exhibit pathogenicity. Although the genome of an industrial enzyme-producing A. niger strain (CBS 513.88) has already been sequenced, the versatility and diversity of this species compel additional exploration. We therefore undertook whole- genome sequencing of the acidogenic A. niger wild-type strain (ATCC 1015) and produced a genome sequence of very high quality. Only 15 gaps are present in the sequence, and half the telomeric regions have been elucidated. Moreover, sequence information from ATCC 1015 was used to improve the genome sequence of CBS 513.88. Chromosome-level comparisons uncovered several genome rearrangements, deletions, a clear case of strain-specific horizontal gene transfer, and identi- fication of 0.8 Mb of novel sequence. Single nucleotide polymorphisms per kilobase (SNPs/kb) between the two strains were found to be exceptionally high (average: 7.8, maximum: 160 SNPs/kb). High variation within the species was con- firmed with exo-metabolite profiling and phylogenetics. Detailed lists of alleles were generated, and genotypic differences were observed to accumulate in metabolic pathways essential to acid production and protein synthesis. A transcriptome analysis supported up-regulation of genes associated with biosynthesis of amino acids that are abundant in glucoamylase A, tRNA-synthases, and protein transporters in the protein producing CBS 513.88 strain. Our results and data sets from this integrative systems biology analysis resulted in a snapshot of fungal evolution and will support further optimization of cell factories based on filamentous fungi.

Published
2011

4. Comparative genomics of citric-acid-producing Aspergillus niger ATCC 1015 versus enzyme-producing CBS 513.88

Author

Andersen, Mikael Rørdam, Salazar, Margarita Pena, Schaap, Peter J., van de Vondervoort, Peter J. I., Culley, David, Thykær, Jette, Frisvad, Jens Christian, Nielsen, Kristian Fog, Albang, Richard, Albermann, Kaj, Berka, Randy M., Braus, Gerhard H., Braus-Stromeyer, Susanna A., Corrochano, Luis M., Dai, Ziyu, van Dijck, Piet W.M., Hofmann, Gerald, Lasure, Linda L., Magnuson, Jon K., Menke, Hildegard, Meijer, Martin, Meijer, Susan Lisette, Nielsen, Jakob Blæsbjerg, Nielsen, Michael Lynge, van Ooyen, Albert J.J., Pel, Herman J., Poulsen, Lars, Samson, Rob A., Stam, Hein, Tsang, Adrian, van den Brink, Johannes M., Atkins, Alex, Aerts, Andrea, Shapiro, Harris, Pangilinan, Jasmyn, Salamov, Asaf, Lou, Yigong, Lindquist, Erika, Lucas, Susan, Grimwood, Jane, Grigoriev, Igor V., Kubicek, Christian P., Martinez, Diego, van Peij, Noël N. M. E., Roubos, Johannes A., Nielsen, Jens, Baker, Scott E., Andersen, Mikael Rørdam, Salazar, Margarita Pena, Schaap, Peter J., van de Vondervoort, Peter J. I., Culley, David, Thykær, Jette, Frisvad, Jens Christian, Nielsen, Kristian Fog, Albang, Richard, Albermann, Kaj, Berka, Randy M., Braus, Gerhard H., Braus-Stromeyer, Susanna A., Corrochano, Luis M., Dai, Ziyu, van Dijck, Piet W.M., Hofmann, Gerald, Lasure, Linda L., Magnuson, Jon K., Menke, Hildegard, Meijer, Martin, Meijer, Susan Lisette, Nielsen, Jakob Blæsbjerg, Nielsen, Michael Lynge, van Ooyen, Albert J.J., Pel, Herman J., Poulsen, Lars, Samson, Rob A., Stam, Hein, Tsang, Adrian, van den Brink, Johannes M., Atkins, Alex, Aerts, Andrea, Shapiro, Harris, Pangilinan, Jasmyn, Salamov, Asaf, Lou, Yigong, Lindquist, Erika, Lucas, Susan, Grimwood, Jane, Grigoriev, Igor V., Kubicek, Christian P., Martinez, Diego, van Peij, Noël N. M. E., Roubos, Johannes A., Nielsen, Jens, and Baker, Scott E.

Abstract

The filamentous fungus Aspergillus niger exhibits great diversity in its phenotype. It is found globally, both as marine and terrestrial strains, produces both organic acids and hydrolytic enzymes in high amounts, and some isolates exhibit pathogenicity. Although the genome of an industrial enzyme-producing A. niger strain (CBS 513.88) has already been sequenced, the versatility and diversity of this species compel additional exploration. We therefore undertook whole-genome sequencing of the acidogenic A. niger wild-type strain (ATCC 1015) and produced a genome sequence of very high quality. Only 15 gaps are present in the sequence, and half the telomeric regions have been elucidated. Moreover, sequence information from ATCC 1015 was used to improve the genome sequence of CBS 513.88. Chromosome-level comparisons uncovered several genome rearrangements, deletions, a clear case of strain-specific horizontal gene transfer, and identification of 0.8 Mb of novel sequence. Single nucleotide polymorphisms per kilobase (SNPs/kb) between the two strains were found to be exceptionally high (average: 7.8, maximum: 160 SNPs/kb). High variation within the species was confirmed with exo-metabolite profiling and phylogenetics. Detailed lists of alleles were generated, and genotypic differences were observed to accumulate in metabolic pathways essential to acid production and protein synthesis. A transcriptome analysis supported up-regulation of genes associated with biosynthesis of amino acids that are abundant in glucoamylase A, tRNA-synthases, and protein transporters in the protein producing CBS 513.88 strain. Our results and data sets from this integrative systems biology analysis resulted in a snapshot of fungal evolution and will support further optimization of cell factories based on filamentous fungi.

Published
2011

5. Genome sequencing and analysis of the versatile cell factory Aspergillus niger CBS 513.88

Author

Pel, Herman J., de Winde, Johannes H., Archer, David B., Dyer, Paul S., Hofmann, Gerald, Schaap, Peter J., Turner, Geoffrey, de Vries, Ronald P., Albang, Richard, Albermann, Kaj, Andersen, Mikael R., Bendtsen, Jannick D., Benen, Jacques A. E., van den Berg, Marco, Breestraat, Stefaan, Caddick, Mark X., Contreras, Roland, Cornell, Michael, Coutinho, Pedro M., Danchin, Etienne G. J., Debets, Alfons J. M., Dekker, Peter, van Dijck, Piet W. M., van Dijk, Alard, Dijkhuizen, Lubbert, Driessen, Arnold J. M., d'Enfert, Christophe, Geysens, Steven, Goosen, Coenie, Groot, Gert S. P., de Groot, Piet W. J., Guillemette, Thomas, Henrissat, Bernard, Herweijer, Marga, van den Hombergh, Johannes P. T. W., van den Hondel, Cees A. M. J. J., van der Heijden, Rene T. J. M., van der Kaaij, Rachel M., Klis, Frans M., Kools, Harrie J., Kubicek, Christian P., van Kuyk, Patricia A., Lauber, Juergen, Lu, Xin, van der Maarel, Marc J. E. C., Meulenberg, Rogier, Menke, Hildegard, Mortimer, Martin A., Nielsen, Jens, Oliver, Stephen G., Olsthoorn, Maurien, Pal, Karoly, van Peij, Noel N. M. E., Ram, Arthur F. J., Rinas, Ursula, Roubos, Johannes A., Sagt, Cees M. J., Schmoll, Monika, Sun, Jibin, Ussery, David, Varga, Janos, Vervecken, Wouter, de Vondervoort, Peter J. J. van, Wedler, Holger, Wosten, Han A. B., Zeng, An-Ping, van Ooyen, Albert J. J., Visser, Jaap, Stam, Hein, Pel, Herman J., de Winde, Johannes H., Archer, David B., Dyer, Paul S., Hofmann, Gerald, Schaap, Peter J., Turner, Geoffrey, de Vries, Ronald P., Albang, Richard, Albermann, Kaj, Andersen, Mikael R., Bendtsen, Jannick D., Benen, Jacques A. E., van den Berg, Marco, Breestraat, Stefaan, Caddick, Mark X., Contreras, Roland, Cornell, Michael, Coutinho, Pedro M., Danchin, Etienne G. J., Debets, Alfons J. M., Dekker, Peter, van Dijck, Piet W. M., van Dijk, Alard, Dijkhuizen, Lubbert, Driessen, Arnold J. M., d'Enfert, Christophe, Geysens, Steven, Goosen, Coenie, Groot, Gert S. P., de Groot, Piet W. J., Guillemette, Thomas, Henrissat, Bernard, Herweijer, Marga, van den Hombergh, Johannes P. T. W., van den Hondel, Cees A. M. J. J., van der Heijden, Rene T. J. M., van der Kaaij, Rachel M., Klis, Frans M., Kools, Harrie J., Kubicek, Christian P., van Kuyk, Patricia A., Lauber, Juergen, Lu, Xin, van der Maarel, Marc J. E. C., Meulenberg, Rogier, Menke, Hildegard, Mortimer, Martin A., Nielsen, Jens, Oliver, Stephen G., Olsthoorn, Maurien, Pal, Karoly, van Peij, Noel N. M. E., Ram, Arthur F. J., Rinas, Ursula, Roubos, Johannes A., Sagt, Cees M. J., Schmoll, Monika, Sun, Jibin, Ussery, David, Varga, Janos, Vervecken, Wouter, de Vondervoort, Peter J. J. van, Wedler, Holger, Wosten, Han A. B., Zeng, An-Ping, van Ooyen, Albert J. J., Visser, Jaap, and Stam, Hein

Abstract

The filamentous fungus Aspergillus niger is widely exploited by the fermentation industry for the production of enzymes and organic acids, particularly citric acid. We sequenced the 33.9-megabase genome of A. niger CBS 513.88, the ancestor of currently used enzyme production strains. A high level of synteny was observed with other aspergilli sequenced. Strong function predictions were made for 6,506 of the 14,165 open reading frames identified. A detailed description of the components of the protein secretion pathway was made and striking differences in the hydrolytic enzyme spectra of aspergilli were observed. A reconstructed metabolic network comprising 1,069 unique reactions illustrates the versatile metabolism of A. niger. Noteworthy is the large number of major facilitator superfamily transporters and fungal zinc binuclear cluster transcription factors, and the presence of putative gene clusters for fumonisin and ochratoxin A synthesis.

Published
2007

6. Genome sequencing and analysis of the versatile cell factory Aspergillus niger CBS 513.88

Author

Sub Molecular Microbiology, Molecular Microbiology, Pel, Herman J., de Winde, Johannes H., Archer, David B., Dyer, Paul S., Hofmann, Gerald, Schaap, Peter J., Turner, Geoffrey, de Vries, Ronald P., Albang, Richard, Albermann, Kaj, Andersen, Mikael R., Bendtsen, Jannick D., Benen, Jacques A. E., van den Berg, Marco, Breestraat, Stefaan, Caddick, Mark X., Contreras, Roland, Cornell, Michael, Coutinho, Pedro M., Danchin, Etienne G. J., Debets, Alfons J. M., Dekker, Peter, van Dijck, Piet W. M., van Dijk, Alard, Dijkhuizen, Lubbert, Driessen, Arnold J. M., d'Enfert, Christophe, Geysens, Steven, Goosen, Coenie, Groot, Gert S. P., de Groot, Piet W. J., Guillemette, Thomas, Henrissat, Bernard, Herweijer, Marga, van den Hombergh, Johannes P. T. W., van den Hondel, Cees A. M. J. J., van der Heijden, Rene T. J. M., van der Kaaij, Rachel M., Klis, Frans M., Kools, Harrie J., Kubicek, Christian P., van Kuyk, Patricia A., Lauber, Juergen, Lu, Xin, van der Maarel, Marc J. E. C., Meulenberg, Rogier, Menke, Hildegard, Mortimer, Martin A., Nielsen, Jens, Oliver, Stephen G., Olsthoorn, Maurien, Pal, Karoly, van Peij, Noel N. M. E., Ram, Arthur F. J., Rinas, Ursula, Roubos, Johannes A., Sagt, Cees M. J., Schmoll, Monika, Sun, Jibin, Ussery, David, Varga, Janos, Vervecken, Wouter, de Vondervoort, Peter J. J. van, Wedler, Holger, Wosten, Han A. B., Zeng, An-Ping, van Ooyen, Albert J. J., Visser, Jaap, Stam, Hein, Sub Molecular Microbiology, Molecular Microbiology, Pel, Herman J., de Winde, Johannes H., Archer, David B., Dyer, Paul S., Hofmann, Gerald, Schaap, Peter J., Turner, Geoffrey, de Vries, Ronald P., Albang, Richard, Albermann, Kaj, Andersen, Mikael R., Bendtsen, Jannick D., Benen, Jacques A. E., van den Berg, Marco, Breestraat, Stefaan, Caddick, Mark X., Contreras, Roland, Cornell, Michael, Coutinho, Pedro M., Danchin, Etienne G. J., Debets, Alfons J. M., Dekker, Peter, van Dijck, Piet W. M., van Dijk, Alard, Dijkhuizen, Lubbert, Driessen, Arnold J. M., d'Enfert, Christophe, Geysens, Steven, Goosen, Coenie, Groot, Gert S. P., de Groot, Piet W. J., Guillemette, Thomas, Henrissat, Bernard, Herweijer, Marga, van den Hombergh, Johannes P. T. W., van den Hondel, Cees A. M. J. J., van der Heijden, Rene T. J. M., van der Kaaij, Rachel M., Klis, Frans M., Kools, Harrie J., Kubicek, Christian P., van Kuyk, Patricia A., Lauber, Juergen, Lu, Xin, van der Maarel, Marc J. E. C., Meulenberg, Rogier, Menke, Hildegard, Mortimer, Martin A., Nielsen, Jens, Oliver, Stephen G., Olsthoorn, Maurien, Pal, Karoly, van Peij, Noel N. M. E., Ram, Arthur F. J., Rinas, Ursula, Roubos, Johannes A., Sagt, Cees M. J., Schmoll, Monika, Sun, Jibin, Ussery, David, Varga, Janos, Vervecken, Wouter, de Vondervoort, Peter J. J. van, Wedler, Holger, Wosten, Han A. B., Zeng, An-Ping, van Ooyen, Albert J. J., Visser, Jaap, and Stam, Hein

Published
2007

7. Comparative genomics of citric-acid-producing Aspergillus niger ATCC 1015 versus enzyme-producing CBS 513.88

Author

Andersen, Mikael R., primary, Salazar, Margarita P., additional, Schaap, Peter J., additional, van de Vondervoort, Peter J.I., additional, Culley, David, additional, Thykaer, Jette, additional, Frisvad, Jens C., additional, Nielsen, Kristian F., additional, Albang, Richard, additional, Albermann, Kaj, additional, Berka, Randy M., additional, Braus, Gerhard H., additional, Braus-Stromeyer, Susanna A., additional, Corrochano, Luis M., additional, Dai, Ziyu, additional, van Dijck, Piet W.M., additional, Hofmann, Gerald, additional, Lasure, Linda L., additional, Magnuson, Jon K., additional, Menke, Hildegard, additional, Meijer, Martin, additional, Meijer, Susan L., additional, Nielsen, Jakob B., additional, Nielsen, Michael L., additional, van Ooyen, Albert J.J., additional, Pel, Herman J., additional, Poulsen, Lars, additional, Samson, Rob A., additional, Stam, Hein, additional, Tsang, Adrian, additional, van den Brink, Johannes M., additional, Atkins, Alex, additional, Aerts, Andrea, additional, Shapiro, Harris, additional, Pangilinan, Jasmyn, additional, Salamov, Asaf, additional, Lou, Yigong, additional, Lindquist, Erika, additional, Lucas, Susan, additional, Grimwood, Jane, additional, Grigoriev, Igor V., additional, Kubicek, Christian P., additional, Martinez, Diego, additional, van Peij, Noël N.M.E., additional, Roubos, Johannes A., additional, Nielsen, Jens, additional, and Baker, Scott E., additional

Published
2011
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9. Genome sequencing and analysis of the versatile cell factory Aspergillus niger CBS 513.88

Author

Pel, Herman J, primary, de Winde, Johannes H, additional, Archer, David B, additional, Dyer, Paul S, additional, Hofmann, Gerald, additional, Schaap, Peter J, additional, Turner, Geoffrey, additional, de Vries, Ronald P, additional, Albang, Richard, additional, Albermann, Kaj, additional, Andersen, Mikael R, additional, Bendtsen, Jannick D, additional, Benen, Jacques A E, additional, van den Berg, Marco, additional, Breestraat, Stefaan, additional, Caddick, Mark X, additional, Contreras, Roland, additional, Cornell, Michael, additional, Coutinho, Pedro M, additional, Danchin, Etienne G J, additional, Debets, Alfons J M, additional, Dekker, Peter, additional, van Dijck, Piet W M, additional, van Dijk, Alard, additional, Dijkhuizen, Lubbert, additional, Driessen, Arnold J M, additional, d'Enfert, Christophe, additional, Geysens, Steven, additional, Goosen, Coenie, additional, Groot, Gert S P, additional, de Groot, Piet W J, additional, Guillemette, Thomas, additional, Henrissat, Bernard, additional, Herweijer, Marga, additional, van den Hombergh, Johannes P T W, additional, van den Hondel, Cees A M J J, additional, van der Heijden, Rene T J M, additional, van der Kaaij, Rachel M, additional, Klis, Frans M, additional, Kools, Harrie J, additional, Kubicek, Christian P, additional, van Kuyk, Patricia A, additional, Lauber, Jürgen, additional, Lu, Xin, additional, van der Maarel, Marc J E C, additional, Meulenberg, Rogier, additional, Menke, Hildegard, additional, Mortimer, Martin A, additional, Nielsen, Jens, additional, Oliver, Stephen G, additional, Olsthoorn, Maurien, additional, Pal, Karoly, additional, van Peij, Noël N M E, additional, Ram, Arthur F J, additional, Rinas, Ursula, additional, Roubos, Johannes A, additional, Sagt, Cees M J, additional, Schmoll, Monika, additional, Sun, Jibin, additional, Ussery, David, additional, Varga, Janos, additional, Vervecken, Wouter, additional, van de Vondervoort, Peter J J, additional, Wedler, Holger, additional, Wösten, Han A B, additional, Zeng, An-Ping, additional, van Ooyen, Albert J J, additional, Visser, Jaap, additional, and Stam, Hein, additional

Published
2007
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