Adding extra letters to the genetic code, in the form of non-natural nucleotides, makes it possible to encode 'exotic' amino acids in new codon triplets.
But any extra, non-natural nucleotides must be recognised by a cell's replication and transcription machinery, otherwise the goal of synthetic biology would not be met. This means that the structure of DNA containing such nucleotides cannot be altered significantly.
Structures of DNA containing two non-natural nucleotides, termed 'Z' and 'P', have recently been determined, showing that they don't perturb the overall architecture of the iconic DNA doule helix. Z and P base pair with a standard Watson-Crick geometry. Short lengths of DNA containing this base pair, or several of them, can adopt both B- and A-form structures.
Addition of these two extra nucleotides to the existing four letter alphabet of A, T, C and G would increases the number of codons, or genetic 'words' from 64 to 216.
These structures, PDB entries , , and are described in a paper by Georgiadis et al. in JACS: DOI:
