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Engineering tRNA abundances for synthetic cellular systems
Routinizing the engineering of synthetic cells requires specifying beforehand how many of each molecule are needed. Physics-based tools for estimating desired molecular abundances in whole-cell synthetic biology are missing. Here, we use a colloidal dynamics simulator to make predictions for how tRN...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10390467/ https://www.ncbi.nlm.nih.gov/pubmed/37524714 http://dx.doi.org/10.1038/s41467-023-40199-9 |
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author | Maheshwari, Akshay J. Calles, Jonathan Waterton, Sean K. Endy, Drew |
author_facet | Maheshwari, Akshay J. Calles, Jonathan Waterton, Sean K. Endy, Drew |
author_sort | Maheshwari, Akshay J. |
collection | PubMed |
description | Routinizing the engineering of synthetic cells requires specifying beforehand how many of each molecule are needed. Physics-based tools for estimating desired molecular abundances in whole-cell synthetic biology are missing. Here, we use a colloidal dynamics simulator to make predictions for how tRNA abundances impact protein synthesis rates. We use rational design and direct RNA synthesis to make 21 synthetic tRNA surrogates from scratch. We use evolutionary algorithms within a computer aided design framework to engineer translation systems predicted to work faster or slower depending on tRNA abundance differences. We build and test the so-specified synthetic systems and find qualitative agreement between expected and observed systems. First principles modeling combined with bottom-up experiments can help molecular-to-cellular scale synthetic biology realize design-build-work frameworks that transcend tinker-and-test. |
format | Online Article Text |
id | pubmed-10390467 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-103904672023-08-02 Engineering tRNA abundances for synthetic cellular systems Maheshwari, Akshay J. Calles, Jonathan Waterton, Sean K. Endy, Drew Nat Commun Article Routinizing the engineering of synthetic cells requires specifying beforehand how many of each molecule are needed. Physics-based tools for estimating desired molecular abundances in whole-cell synthetic biology are missing. Here, we use a colloidal dynamics simulator to make predictions for how tRNA abundances impact protein synthesis rates. We use rational design and direct RNA synthesis to make 21 synthetic tRNA surrogates from scratch. We use evolutionary algorithms within a computer aided design framework to engineer translation systems predicted to work faster or slower depending on tRNA abundance differences. We build and test the so-specified synthetic systems and find qualitative agreement between expected and observed systems. First principles modeling combined with bottom-up experiments can help molecular-to-cellular scale synthetic biology realize design-build-work frameworks that transcend tinker-and-test. Nature Publishing Group UK 2023-07-31 /pmc/articles/PMC10390467/ /pubmed/37524714 http://dx.doi.org/10.1038/s41467-023-40199-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Maheshwari, Akshay J. Calles, Jonathan Waterton, Sean K. Endy, Drew Engineering tRNA abundances for synthetic cellular systems |
title | Engineering tRNA abundances for synthetic cellular systems |
title_full | Engineering tRNA abundances for synthetic cellular systems |
title_fullStr | Engineering tRNA abundances for synthetic cellular systems |
title_full_unstemmed | Engineering tRNA abundances for synthetic cellular systems |
title_short | Engineering tRNA abundances for synthetic cellular systems |
title_sort | engineering trna abundances for synthetic cellular systems |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10390467/ https://www.ncbi.nlm.nih.gov/pubmed/37524714 http://dx.doi.org/10.1038/s41467-023-40199-9 |
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