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

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

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    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.
    Original languageEnglish
    JournalGenome Research
    Issue number6
    Pages (from-to)885-897
    Publication statusPublished - 2011

    Bibliographical note

    Supplemental material is available for this article. The A. niger ATCC 1015 whole genome sequence has been submitted to GenBank ( under accession no. ACJE00000000. The sequence data from the phylogeny study have been submitted to GenBank under accession nos. GU296686–GU296739. The microarray data from this study have been submitted to the NCBI Gene Expression Omnibus (GEO) ( under series accession no. GSE10983. The dsmM_ANIGERa_coll511030F library and platform information have been submitted to GEO under accession no. GPL6758.


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