Gene deletion of cytosolic ATP: citrate lyase leads to altered organic acid production in Aspergillus niger

Susan Lisette Meijer, Michael Lynge Nielsen, Lisbeth Olsson, Jens Nielsen

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    With the availability of the genome sequence of the filamentous fungus Aspergillus niger, the use of targeted genetic modifications has become feasible. This, together with the fact that A. niger is well established industrially, makes this fungus an attractive micro-organism for creating a cell factory platform for production of chemicals. Using molecular biology techniques, this study focused on metabolic engineering of A. niger to manipulate its organic acid production in the direction of succinic acid. The gene target for complete gene deletion was cytosolic ATP: citrate lyase (acl), which had previously been identified by using genome-scale stoichiometric metabolic model simulations. The acl gene was deleted using the bipartite gene-targeting method, and the mutant was characterized in batch cultivation. It was found that the succinic acid yield was increased threefold by deleting the acl gene. Additionally, the total amount of organic acids produced in the deletion strain was significantly increased. Genome-scale stoichiometric metabolic model predictions can be used for identifying gene targets. Deletion of the acl led to increased succinic acid production by A. niger.
    Original languageEnglish
    JournalJournal of Industrial Microbiology and Biotechnology
    Volume36
    Pages (from-to)1275-1280
    ISSN1367-5435
    DOIs
    Publication statusPublished - 2009

    Cite this

    @article{9676f549db2a4acab7917a773f35517a,
    title = "Gene deletion of cytosolic ATP: citrate lyase leads to altered organic acid production in Aspergillus niger",
    abstract = "With the availability of the genome sequence of the filamentous fungus Aspergillus niger, the use of targeted genetic modifications has become feasible. This, together with the fact that A. niger is well established industrially, makes this fungus an attractive micro-organism for creating a cell factory platform for production of chemicals. Using molecular biology techniques, this study focused on metabolic engineering of A. niger to manipulate its organic acid production in the direction of succinic acid. The gene target for complete gene deletion was cytosolic ATP: citrate lyase (acl), which had previously been identified by using genome-scale stoichiometric metabolic model simulations. The acl gene was deleted using the bipartite gene-targeting method, and the mutant was characterized in batch cultivation. It was found that the succinic acid yield was increased threefold by deleting the acl gene. Additionally, the total amount of organic acids produced in the deletion strain was significantly increased. Genome-scale stoichiometric metabolic model predictions can be used for identifying gene targets. Deletion of the acl led to increased succinic acid production by A. niger.",
    author = "Meijer, {Susan Lisette} and Nielsen, {Michael Lynge} and Lisbeth Olsson and Jens Nielsen",
    year = "2009",
    doi = "10.1007/s10295-009-0607-y",
    language = "English",
    volume = "36",
    pages = "1275--1280",
    journal = "Journal of Industrial Microbiology and Biotechnology",
    issn = "1367-5435",
    publisher = "Springer",

    }

    Gene deletion of cytosolic ATP: citrate lyase leads to altered organic acid production in Aspergillus niger. / Meijer, Susan Lisette; Nielsen, Michael Lynge; Olsson, Lisbeth; Nielsen, Jens.

    In: Journal of Industrial Microbiology and Biotechnology, Vol. 36, 2009, p. 1275-1280.

    Research output: Contribution to journalJournal articleResearchpeer-review

    TY - JOUR

    T1 - Gene deletion of cytosolic ATP: citrate lyase leads to altered organic acid production in Aspergillus niger

    AU - Meijer, Susan Lisette

    AU - Nielsen, Michael Lynge

    AU - Olsson, Lisbeth

    AU - Nielsen, Jens

    PY - 2009

    Y1 - 2009

    N2 - With the availability of the genome sequence of the filamentous fungus Aspergillus niger, the use of targeted genetic modifications has become feasible. This, together with the fact that A. niger is well established industrially, makes this fungus an attractive micro-organism for creating a cell factory platform for production of chemicals. Using molecular biology techniques, this study focused on metabolic engineering of A. niger to manipulate its organic acid production in the direction of succinic acid. The gene target for complete gene deletion was cytosolic ATP: citrate lyase (acl), which had previously been identified by using genome-scale stoichiometric metabolic model simulations. The acl gene was deleted using the bipartite gene-targeting method, and the mutant was characterized in batch cultivation. It was found that the succinic acid yield was increased threefold by deleting the acl gene. Additionally, the total amount of organic acids produced in the deletion strain was significantly increased. Genome-scale stoichiometric metabolic model predictions can be used for identifying gene targets. Deletion of the acl led to increased succinic acid production by A. niger.

    AB - With the availability of the genome sequence of the filamentous fungus Aspergillus niger, the use of targeted genetic modifications has become feasible. This, together with the fact that A. niger is well established industrially, makes this fungus an attractive micro-organism for creating a cell factory platform for production of chemicals. Using molecular biology techniques, this study focused on metabolic engineering of A. niger to manipulate its organic acid production in the direction of succinic acid. The gene target for complete gene deletion was cytosolic ATP: citrate lyase (acl), which had previously been identified by using genome-scale stoichiometric metabolic model simulations. The acl gene was deleted using the bipartite gene-targeting method, and the mutant was characterized in batch cultivation. It was found that the succinic acid yield was increased threefold by deleting the acl gene. Additionally, the total amount of organic acids produced in the deletion strain was significantly increased. Genome-scale stoichiometric metabolic model predictions can be used for identifying gene targets. Deletion of the acl led to increased succinic acid production by A. niger.

    U2 - 10.1007/s10295-009-0607-y

    DO - 10.1007/s10295-009-0607-y

    M3 - Journal article

    VL - 36

    SP - 1275

    EP - 1280

    JO - Journal of Industrial Microbiology and Biotechnology

    JF - Journal of Industrial Microbiology and Biotechnology

    SN - 1367-5435

    ER -