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.
authors: Department for Systems Biology, Center for Microbial Biotechnology, Technical University of Denmark, Building 223, 2800 Lyngby, Denmark. SuLM@novozymes.com
authors: Susan
authors: S
authors: Meijer
authors: Michael Lynge
authors: ML
authors: Nielsen
authors: Lisbeth
authors: L
authors: Olsson
authors: Jens
authors: J
authors: Nielsen
mesh_terms: D001275:ATP Citrate (pro-S)-Lyase / Q000235:genetics* / Q000378:metabolism; D001234:Aspergillus niger / Q000235:genetics* / Q000378:metabolism*; D017353:Gene Deletion; D005800:Genes, Fungal / Q000235:genetics; D005947:Glucose / Q000378:metabolism; D019802:Succinic Acid / Q000378:metabolism*; D014994:Xylose / Q000378:metabolism
chemical_list: D014994:Xylose; D019802:Succinic Acid; D001275:ATP Citrate (pro-S)-Lyase; D005947:Glucose