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Algorithms for ribosome traffic engineering and their potential in improving host cells' titer and growth rate

mRNA translation is a fundamental cellular process consuming most of the intracellular energy; thus, it is under extensive evolutionary selection for optimization, and its efficiency can affect the host's growth rate. We describe a generic approach for improving the growth rate (fitness) of any...

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Autores principales: Zur, Hadas, Cohen-Kupiec, Rachel, Vinokour, Sophie, Tuller, Tamir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713304/
https://www.ncbi.nlm.nih.gov/pubmed/33273552
http://dx.doi.org/10.1038/s41598-020-78260-y
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author Zur, Hadas
Cohen-Kupiec, Rachel
Vinokour, Sophie
Tuller, Tamir
author_facet Zur, Hadas
Cohen-Kupiec, Rachel
Vinokour, Sophie
Tuller, Tamir
author_sort Zur, Hadas
collection PubMed
description mRNA translation is a fundamental cellular process consuming most of the intracellular energy; thus, it is under extensive evolutionary selection for optimization, and its efficiency can affect the host's growth rate. We describe a generic approach for improving the growth rate (fitness) of any organism by introducing synonymous mutations based on comprehensive computational models. The algorithms introduce silent mutations that may improve the allocation of ribosomes in the cells via the decreasing of their traffic jams during translation respectively. As a result, resources availability in the cell changes leading to improved growth-rate. We demonstrate experimentally the implementation of the method on Saccharomyces cerevisiae: we show that by introducing a few mutations in two computationally selected genes the mutant's titer increased. Our approach can be employed for improving the growth rate of any organism providing the existence of data for inferring models, and with the relevant genomic engineering tools; thus, it is expected to be extremely useful in biotechnology, medicine, and agriculture.
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spelling pubmed-77133042020-12-03 Algorithms for ribosome traffic engineering and their potential in improving host cells' titer and growth rate Zur, Hadas Cohen-Kupiec, Rachel Vinokour, Sophie Tuller, Tamir Sci Rep Article mRNA translation is a fundamental cellular process consuming most of the intracellular energy; thus, it is under extensive evolutionary selection for optimization, and its efficiency can affect the host's growth rate. We describe a generic approach for improving the growth rate (fitness) of any organism by introducing synonymous mutations based on comprehensive computational models. The algorithms introduce silent mutations that may improve the allocation of ribosomes in the cells via the decreasing of their traffic jams during translation respectively. As a result, resources availability in the cell changes leading to improved growth-rate. We demonstrate experimentally the implementation of the method on Saccharomyces cerevisiae: we show that by introducing a few mutations in two computationally selected genes the mutant's titer increased. Our approach can be employed for improving the growth rate of any organism providing the existence of data for inferring models, and with the relevant genomic engineering tools; thus, it is expected to be extremely useful in biotechnology, medicine, and agriculture. Nature Publishing Group UK 2020-12-03 /pmc/articles/PMC7713304/ /pubmed/33273552 http://dx.doi.org/10.1038/s41598-020-78260-y Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zur, Hadas
Cohen-Kupiec, Rachel
Vinokour, Sophie
Tuller, Tamir
Algorithms for ribosome traffic engineering and their potential in improving host cells' titer and growth rate
title Algorithms for ribosome traffic engineering and their potential in improving host cells' titer and growth rate
title_full Algorithms for ribosome traffic engineering and their potential in improving host cells' titer and growth rate
title_fullStr Algorithms for ribosome traffic engineering and their potential in improving host cells' titer and growth rate
title_full_unstemmed Algorithms for ribosome traffic engineering and their potential in improving host cells' titer and growth rate
title_short Algorithms for ribosome traffic engineering and their potential in improving host cells' titer and growth rate
title_sort algorithms for ribosome traffic engineering and their potential in improving host cells' titer and growth rate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713304/
https://www.ncbi.nlm.nih.gov/pubmed/33273552
http://dx.doi.org/10.1038/s41598-020-78260-y
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