Codon optimization in protein-coding sequences (CDSs) is a widely used technique to promote the heterologous expression of target genes. In codon optimization, a combinatorial space of nucleotide sequences that code a given amino acid sequence and take into account user-prescribed forbidden sequence motifs is explored to optimize multiple criteria. Although evolutionary algorithms have been used to tackle such complex codon optimization problems, evolutionary codon optimization tools do not provide guarantees to find the optimal solutions for these multicriteria codon optimization problems.
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