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The Extension of the Standard Genetic Code via Optimal Codon Blocks Division

: The standard genetic code (SGC) is a crucial biological system, which allows to transmit genetic information from DNA sequences to the protein world. The idea of the optimal extension of the SGC with new information appears especially interesting in the context of successful experimental achievements in reprogramming of this code. The aim of this code engineering is incorporating non-canonical amino acids (ncAAs) into synthesised artiﬁcial proteins with novel functions. Such molecules open new perspectives in medicine, chemistry and biotechnology. Several methods extending the canonical coding system were proposed. Here, we would like to investigate a problem of the optimal genetic code extension using graph theory methodology. We measured the quality of considered coding systems applying the set conductance, which determines the robustness level against point mutations of individual codon blocks encoding the same information. Thanks to that, we were able to ﬁnd several possible optimal extensions of the SGC based on utilization of the codons redundant in the original code. We found codes that could encode up to 16 ncAAs and simultaneously code for 20 canonical amino acids and one stop translation signal. One of these codes was the most balanced, i.e. it consisted of the canonical set and the extended set that were characterized by the same level of robustness against point mutations. The proposed codes could be helpful in experimental construction of artiﬁcial genetic codes, which can encode new amino acid with new useful properties.