Engineering a riboswitch-based genetic platform for the self-directed evolution of acid-tolerant phenotypes
Environmental pH is a fundamental signal continuously directing the metabolism and behavior of living cells. Programming the precise cellular response toward environmental pH is, therefore, crucial for engineering cells for increasingly sophisticated functions. Herein, we engineer a set of riboswitc...
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| Published in | Nature communications Vol. 8; no. 1; pp. 411 - 12 |
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| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
04.09.2017
Nature Publishing Group Nature Portfolio |
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| Online Access | Get full text |
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| Abstract | Environmental pH is a fundamental signal continuously directing the metabolism and behavior of living cells. Programming the precise cellular response toward environmental pH is, therefore, crucial for engineering cells for increasingly sophisticated functions. Herein, we engineer a set of riboswitch-based pH-sensing genetic devices to enable the control of gene expression according to differential environmental pH. We next develop a digital pH-sensing system to utilize the analogue-sensing behavior of these devices for high-resolution recording of host cell exposure to discrete external pH levels. The application of this digital pH-sensing system is demonstrated in a genetic program that autonomously regulated the evolutionary engineering of host cells for improved tolerance to a broad spectrum of organic acids, a valuable phenotype for metabolic engineering and bioremediation applications.
Cells are exposed to shifts in environmental pH, which direct their metabolism and behavior. Here the authors design pH-sensing riboswitches to create a gene expression program, digitalize the system to respond to a narrow pH range and apply it to evolve host cells with improved tolerance to a variety of organic acids. |
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| AbstractList | Environmental pH is a fundamental signal continuously directing the metabolism and behavior of living cells. Programming the precise cellular response toward environmental pH is, therefore, crucial for engineering cells for increasingly sophisticated functions. Herein, we engineer a set of riboswitch-based pH-sensing genetic devices to enable the control of gene expression according to differential environmental pH. We next develop a digital pH-sensing system to utilize the analogue-sensing behavior of these devices for high-resolution recording of host cell exposure to discrete external pH levels. The application of this digital pH-sensing system is demonstrated in a genetic program that autonomously regulated the evolutionary engineering of host cells for improved tolerance to a broad spectrum of organic acids, a valuable phenotype for metabolic engineering and bioremediation applications. Environmental pH is a fundamental signal continuously directing the metabolism and behavior of living cells. Programming the precise cellular response toward environmental pH is, therefore, crucial for engineering cells for increasingly sophisticated functions. Herein, we engineer a set of riboswitch-based pH-sensing genetic devices to enable the control of gene expression according to differential environmental pH. We next develop a digital pH-sensing system to utilize the analogue-sensing behavior of these devices for high-resolution recording of host cell exposure to discrete external pH levels. The application of this digital pH-sensing system is demonstrated in a genetic program that autonomously regulated the evolutionary engineering of host cells for improved tolerance to a broad spectrum of organic acids, a valuable phenotype for metabolic engineering and bioremediation applications.Cells are exposed to shifts in environmental pH, which direct their metabolism and behavior. Here the authors design pH-sensing riboswitches to create a gene expression program, digitalize the system to respond to a narrow pH range and apply it to evolve host cells with improved tolerance to a variety of organic acids. Environmental pH is a fundamental signal continuously directing the metabolism and behavior of living cells. Programming the precise cellular response toward environmental pH is, therefore, crucial for engineering cells for increasingly sophisticated functions. Herein, we engineer a set of riboswitch-based pH-sensing genetic devices to enable the control of gene expression according to differential environmental pH. We next develop a digital pH-sensing system to utilize the analogue-sensing behavior of these devices for high-resolution recording of host cell exposure to discrete external pH levels. The application of this digital pH-sensing system is demonstrated in a genetic program that autonomously regulated the evolutionary engineering of host cells for improved tolerance to a broad spectrum of organic acids, a valuable phenotype for metabolic engineering and bioremediation applications. Cells are exposed to shifts in environmental pH, which direct their metabolism and behavior. Here the authors design pH-sensing riboswitches to create a gene expression program, digitalize the system to respond to a narrow pH range and apply it to evolve host cells with improved tolerance to a variety of organic acids. Cells are exposed to shifts in environmental pH, which direct their metabolism and behavior. Here the authors design pH-sensing riboswitches to create a gene expression program, digitalize the system to respond to a narrow pH range and apply it to evolve host cells with improved tolerance to a variety of organic acids. |
| ArticleNumber | 411 |
| Author | Pham, Hoang Long Wong, Adison Chua, Niying Teo, Wei Suong Yew, Wen Shan Chang, Matthew Wook |
| Author_xml | – sequence: 1 givenname: Hoang Long surname: Pham fullname: Pham, Hoang Long organization: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore – sequence: 2 givenname: Adison surname: Wong fullname: Wong, Adison organization: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore, Singapore Institute of Technology – sequence: 3 givenname: Niying surname: Chua fullname: Chua, Niying organization: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore – sequence: 4 givenname: Wei Suong surname: Teo fullname: Teo, Wei Suong organization: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore, School of Life Sciences and Chemical Technology, Ngee Ann Polytechnic – sequence: 5 givenname: Wen Shan surname: Yew fullname: Yew, Wen Shan organization: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore – sequence: 6 givenname: Matthew Wook surname: Chang fullname: Chang, Matthew Wook email: matthew_chang@nuhs.edu.sg organization: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/28871084$$D View this record in MEDLINE/PubMed |
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| Snippet | Environmental pH is a fundamental signal continuously directing the metabolism and behavior of living cells. Programming the precise cellular response toward... Cells are exposed to shifts in environmental pH, which direct their metabolism and behavior. Here the authors design pH-sensing riboswitches to create a gene... |
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| SubjectTerms | 631/553/552 631/61 Acids - pharmacology Biological evolution Directed evolution Directed Molecular Evolution Engineering Escherichia coli - genetics Gene expression Genetic Engineering - methods Genotype Humanities and Social Sciences Hydrogen ions Hydrogen-Ion Concentration Metabolism multidisciplinary Mutation - genetics Organic acids pH effects Phenotype Riboswitch - genetics Riboswitches Science Science (multidisciplinary) |
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| Title | Engineering a riboswitch-based genetic platform for the self-directed evolution of acid-tolerant phenotypes |
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