Basic principles of the genetic code extension

Abstract

Compounds including non-canonical amino acids (ncAAs) or other artificially designed molecules can find a lot of applications in medicine, industry and biotechnology. They can be produced thanks to the modification or extension of the standard genetic code (SGC). Such peptides or proteins including the ncAAs can be constantly delivered in a stable way by organisms with the customized genetic code. Among several methods of engineering the code, using non-canonical base pairs is especially promising, because it enables generating many new codons, which can be used to encode any new amino acid. Since even one pair of new bases can extend the SGC up to 216 codons generated by a six-letter nucleotide alphabet, the extension of the SGC can be achieved in many ways. Here, we proposed a stepwise procedure of the SGC extension with one pair of non-canonical bases to minimize the consequences of point mutations. We reported relationships between codons in the framework of graph theory. All 216 codons were represented as nodes of the graph, whereas its edges were induced by all possible single nucleotide mutations occurring between codons. Therefore, every set of canonical and newly added codons induces a specific subgraph. We characterized the properties of the induced subgraphs generated by selected sets of codons. Thanks to that, we were able to describe a procedure for incremental addition of the set of meaningful codons up to the full coding system consisting of three pairs of bases. The procedure of gradual extension of the SGC makes the whole system robust to changing genetic information due to mutations and is compatible with the views assuming that codons and amino acids were added successively to the primordial SGC, which evolved minimizing harmful consequences of mutations or mistranslations of encoded proteins.

Probing the electronic relaxation pathways and photostability of the synthetic nucleobase Z via laser interfaced mass spectrometry

“…1,2 Interest in this field has increased due to potential biotechnology applications, including the production of novel amino acids, and site-specific tagging of oligonucleotides. 3,4 However, recent work developing non-natural nucleobases and semisynthetic organisms has largely overlooked the photostability of the new nucleobase moieties. This is surprising given the widescale acceptance that the natural DNA nucleobases were selected not just due to their ability to encode genetic information, but also due to their photostability in the presence of UV light.…”

“…This is surprising given the widescale acceptance that the natural DNA nucleobases were selected not just due to their ability to encode genetic information, but also due to their photostability in the presence of UV light. 5,6 Crespo-Hernandez and co-workers have studied the photostability of the synthetic nucleobase dTPT3 ((2-deoxy-b-D-erythropentofuranosyl)-thieno [3,4]pyridine-2-thione), finding that it is a photosensitizer upon the absorption of UVA to near-visible radiation, thus possessing the potential to oxidatively damage DNA and other biomolecules in vivo. 7 Their results have been supported by subsequent theoretical work from Cui and co-workers, 8 and further recent experimental work by Li and co-workers.…”

Computational Analysis of Genetic Code Variations Optimized for the Robustness against Point Mutations with Wobble-like Effects

“…This is of importance in biotechnology as, for instance, it facilitates the development of novel drugs. Recently, Bła żej and colleagues analyzed the extension of the SGC that was inspired by the robustness of the code against point mutations [11].…”