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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....

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Autores principales: Sun, Zhi, Wei, Weijia, Zhang, Mingyue, Shi, Wenjia, Zong, Yeqing, Chen, Yihua, Yang, Xiaojing, Yu, Bo, Tang, Chao, Lou, Chunbo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
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.
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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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