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Synthetic robust perfect adaptation achieved by negative feedback coupling with linear weak positive feedback
Unlike their natural counterparts, synthetic genetic circuits are usually fragile in the face of environmental perturbations and genetic mutations. Several theoretical robust genetic circuits have been designed, but their performance under real-world conditions has not yet been carefully evaluated....
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8887471/ https://www.ncbi.nlm.nih.gov/pubmed/35166832 http://dx.doi.org/10.1093/nar/gkac066 |
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author | Sun, Zhi Wei, Weijia Zhang, Mingyue Shi, Wenjia Zong, Yeqing Chen, Yihua Yang, Xiaojing Yu, Bo Tang, Chao Lou, Chunbo |
author_facet | Sun, Zhi Wei, Weijia Zhang, Mingyue Shi, Wenjia Zong, Yeqing Chen, Yihua Yang, Xiaojing Yu, Bo Tang, Chao Lou, Chunbo |
author_sort | Sun, Zhi |
collection | PubMed |
description | Unlike their natural counterparts, synthetic genetic circuits are usually fragile in the face of environmental perturbations and genetic mutations. Several theoretical robust genetic circuits have been designed, but their performance under real-world conditions has not yet been carefully evaluated. Here, we designed and synthesized a new robust perfect adaptation circuit composed of two-node negative feedback coupling with linear positive feedback on the buffer node. As a key feature, the linear positive feedback was fine-tuned to evaluate its necessity. We found that the desired function was robustly achieved when genetic parameters were varied by systematically perturbing all interacting parts within the topology, and the necessity of the completeness of the topological structures was evaluated by destroying key circuit features. Furthermore, different environmental perturbances were imposed onto the circuit by changing growth rates, carbon metabolic strategies and even chassis cells, and the designed perfect adaptation function was still achieved under all conditions. The successful design of a robust perfect adaptation circuit indicated that the top-down design strategy is capable of predictably guiding bottom-up engineering for robust genetic circuits. This robust adaptation circuit could be integrated as a motif into more complex circuits to robustly implement more sophisticated and critical biological functions. |
format | Online Article Text |
id | pubmed-8887471 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-88874712022-03-02 Synthetic robust perfect adaptation achieved by negative feedback coupling with linear weak positive feedback Sun, Zhi Wei, Weijia Zhang, Mingyue Shi, Wenjia Zong, Yeqing Chen, Yihua Yang, Xiaojing Yu, Bo Tang, Chao Lou, Chunbo Nucleic Acids Res Synthetic Biology and Bioengineering Unlike their natural counterparts, synthetic genetic circuits are usually fragile in the face of environmental perturbations and genetic mutations. Several theoretical robust genetic circuits have been designed, but their performance under real-world conditions has not yet been carefully evaluated. Here, we designed and synthesized a new robust perfect adaptation circuit composed of two-node negative feedback coupling with linear positive feedback on the buffer node. As a key feature, the linear positive feedback was fine-tuned to evaluate its necessity. We found that the desired function was robustly achieved when genetic parameters were varied by systematically perturbing all interacting parts within the topology, and the necessity of the completeness of the topological structures was evaluated by destroying key circuit features. Furthermore, different environmental perturbances were imposed onto the circuit by changing growth rates, carbon metabolic strategies and even chassis cells, and the designed perfect adaptation function was still achieved under all conditions. The successful design of a robust perfect adaptation circuit indicated that the top-down design strategy is capable of predictably guiding bottom-up engineering for robust genetic circuits. This robust adaptation circuit could be integrated as a motif into more complex circuits to robustly implement more sophisticated and critical biological functions. Oxford University Press 2022-02-15 /pmc/articles/PMC8887471/ /pubmed/35166832 http://dx.doi.org/10.1093/nar/gkac066 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Synthetic Biology and Bioengineering Sun, Zhi Wei, Weijia Zhang, Mingyue Shi, Wenjia Zong, Yeqing Chen, Yihua Yang, Xiaojing Yu, Bo Tang, Chao Lou, Chunbo Synthetic robust perfect adaptation achieved by negative feedback coupling with linear weak positive feedback |
title | Synthetic robust perfect adaptation achieved by negative feedback coupling with linear weak positive feedback |
title_full | Synthetic robust perfect adaptation achieved by negative feedback coupling with linear weak positive feedback |
title_fullStr | Synthetic robust perfect adaptation achieved by negative feedback coupling with linear weak positive feedback |
title_full_unstemmed | Synthetic robust perfect adaptation achieved by negative feedback coupling with linear weak positive feedback |
title_short | Synthetic robust perfect adaptation achieved by negative feedback coupling with linear weak positive feedback |
title_sort | synthetic robust perfect adaptation achieved by negative feedback coupling with linear weak positive feedback |
topic | Synthetic Biology and Bioengineering |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8887471/ https://www.ncbi.nlm.nih.gov/pubmed/35166832 http://dx.doi.org/10.1093/nar/gkac066 |
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