| abstract |
The present invention relates to methods for producing a polypeptide, comprising: (a) cultivating a mutant cell under conditions conducive for production of the polypeptide, wherein (i) the mutant cell is related to a parent cell, which parent cell comprises at least two tandem copies of a nucleic acid sequence encoding the polypeptide or a nucleic acid sequence encoding the polypeptide, which nucleic acid sequence comprises repeat sequences at the 5' and 3' ends of the nucleic acid sequence, by the introduction of a nucleic acid construct into the genome of the parent cell at a locus which is within or not within the nucleic acid sequence(s), wherein the introduction of the nucleic acid construct into the locus modifies the copy number of the nucleic acid sequence(s) and the modification of the copy number is not a result of selective pressure; and (ii) the mutant cell produces more or less of the polypeptide than the parent cell when both cells are cultivated under the same conditions; and (b) recovering the poylpeptide from the cultivation medium. The present invention also relates to methods for obtaining a mutant cell and mutant cells. |