The invention relates to a method for optimizing a nucleotide sequence for expression of a protein on the basis of the amino acid sequence of the protein, in which for a particular region there is specification of a test sequence with m optimization positions on which the codon occupation is varied, a quality function being used to ascertain the optimal codon occupation on these optimization positions, and one or more codons of this optimal occupation being specified as codons of the optimized nucleotide sequence. These steps are iterated, with the codons of the optimized nucleotide sequence which are specified in the preceding steps remaining unchanged in subsequent iteration steps. The invention additionally relates to a device for carrying out this method.