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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Bibliographic Details
Published in:Nature communications 2017-09, Vol.8 (1), p.411-12, Article 411
Main Authors: Pham, Hoang Long, Wong, Adison, Chua, Niying, Teo, Wei Suong, Yew, Wen Shan, Chang, Matthew Wook
Format: Article
Language:English
Subjects:
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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Summary: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.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-017-00511-w