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Basic principles of the genetic code extension
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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062095/ https://www.ncbi.nlm.nih.gov/pubmed/32257313 http://dx.doi.org/10.1098/rsos.191384 |
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author | Błażej, Paweł Wnetrzak, Małgorzata Mackiewicz, Dorota Mackiewicz, Paweł |
author_facet | Błażej, Paweł Wnetrzak, Małgorzata Mackiewicz, Dorota Mackiewicz, Paweł |
author_sort | Błażej, Paweł |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7062095 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The Royal Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-70620952020-03-31 Basic principles of the genetic code extension Błażej, Paweł Wnetrzak, Małgorzata Mackiewicz, Dorota Mackiewicz, Paweł R Soc Open Sci Mathematics 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. The Royal Society 2020-02-05 /pmc/articles/PMC7062095/ /pubmed/32257313 http://dx.doi.org/10.1098/rsos.191384 Text en © 2020 The Authors. http://creativecommons.org/licenses/by/4.0/ Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited. |
spellingShingle | Mathematics Błażej, Paweł Wnetrzak, Małgorzata Mackiewicz, Dorota Mackiewicz, Paweł Basic principles of the genetic code extension |
title | Basic principles of the genetic code extension |
title_full | Basic principles of the genetic code extension |
title_fullStr | Basic principles of the genetic code extension |
title_full_unstemmed | Basic principles of the genetic code extension |
title_short | Basic principles of the genetic code extension |
title_sort | basic principles of the genetic code extension |
topic | Mathematics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062095/ https://www.ncbi.nlm.nih.gov/pubmed/32257313 http://dx.doi.org/10.1098/rsos.191384 |
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