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Antagonistic Control of Genetic Circuit Performance for Rapid Analysis of Targeted Enzyme Activity in Living Cells

Genetic circuits have been developed for quantitative measurement of enzyme activity, metabolic engineering of strain development, and dynamic regulation of microbial cells. A genetic circuit consists of several bio-elements, including enzymes and regulatory cassettes, that can generate the desired...

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Autores principales: Kwon, Kil Koang, Kim, Haseong, Yeom, Soo-Jin, Rha, Eugene, Lee, Jinju, Lee, Hyewon, Lee, Dae-Hee, Lee, Seung-Goo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835892/
https://www.ncbi.nlm.nih.gov/pubmed/33511156
http://dx.doi.org/10.3389/fmolb.2020.599878
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author Kwon, Kil Koang
Kim, Haseong
Yeom, Soo-Jin
Rha, Eugene
Lee, Jinju
Lee, Hyewon
Lee, Dae-Hee
Lee, Seung-Goo
author_facet Kwon, Kil Koang
Kim, Haseong
Yeom, Soo-Jin
Rha, Eugene
Lee, Jinju
Lee, Hyewon
Lee, Dae-Hee
Lee, Seung-Goo
author_sort Kwon, Kil Koang
collection PubMed
description Genetic circuits have been developed for quantitative measurement of enzyme activity, metabolic engineering of strain development, and dynamic regulation of microbial cells. A genetic circuit consists of several bio-elements, including enzymes and regulatory cassettes, that can generate the desired output signal, which is then used as a precise criterion for enzyme screening and engineering. Antagonists and inhibitors are small molecules with inhibitory effects on regulators and enzymes, respectively. In this study, an antagonist and an inhibitor were applied to a genetic circuit for a dynamic detection range. We developed a genetic circuit relying on regulators and enzymes, allowing for straightforward control of its output signal without additional genetic modification. We used para-nitrophenol and alanine as an antagonist of DmpR and inhibitor of tyrosine phenol-lyase, respectively. We show that the antagonist resets the detection range of the genetic circuit similarly to a resistor in an electrical logic circuit. These biological resistors in genetic circuits can be used as a rapid and precise controller of variable outputs with minimal circuit configuration.
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spelling pubmed-78358922021-01-27 Antagonistic Control of Genetic Circuit Performance for Rapid Analysis of Targeted Enzyme Activity in Living Cells Kwon, Kil Koang Kim, Haseong Yeom, Soo-Jin Rha, Eugene Lee, Jinju Lee, Hyewon Lee, Dae-Hee Lee, Seung-Goo Front Mol Biosci Molecular Biosciences Genetic circuits have been developed for quantitative measurement of enzyme activity, metabolic engineering of strain development, and dynamic regulation of microbial cells. A genetic circuit consists of several bio-elements, including enzymes and regulatory cassettes, that can generate the desired output signal, which is then used as a precise criterion for enzyme screening and engineering. Antagonists and inhibitors are small molecules with inhibitory effects on regulators and enzymes, respectively. In this study, an antagonist and an inhibitor were applied to a genetic circuit for a dynamic detection range. We developed a genetic circuit relying on regulators and enzymes, allowing for straightforward control of its output signal without additional genetic modification. We used para-nitrophenol and alanine as an antagonist of DmpR and inhibitor of tyrosine phenol-lyase, respectively. We show that the antagonist resets the detection range of the genetic circuit similarly to a resistor in an electrical logic circuit. These biological resistors in genetic circuits can be used as a rapid and precise controller of variable outputs with minimal circuit configuration. Frontiers Media S.A. 2021-01-12 /pmc/articles/PMC7835892/ /pubmed/33511156 http://dx.doi.org/10.3389/fmolb.2020.599878 Text en Copyright © 2021 Kwon, Kim, Yeom, Rha, Lee, Lee, Lee and Lee. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Kwon, Kil Koang
Kim, Haseong
Yeom, Soo-Jin
Rha, Eugene
Lee, Jinju
Lee, Hyewon
Lee, Dae-Hee
Lee, Seung-Goo
Antagonistic Control of Genetic Circuit Performance for Rapid Analysis of Targeted Enzyme Activity in Living Cells
title Antagonistic Control of Genetic Circuit Performance for Rapid Analysis of Targeted Enzyme Activity in Living Cells
title_full Antagonistic Control of Genetic Circuit Performance for Rapid Analysis of Targeted Enzyme Activity in Living Cells
title_fullStr Antagonistic Control of Genetic Circuit Performance for Rapid Analysis of Targeted Enzyme Activity in Living Cells
title_full_unstemmed Antagonistic Control of Genetic Circuit Performance for Rapid Analysis of Targeted Enzyme Activity in Living Cells
title_short Antagonistic Control of Genetic Circuit Performance for Rapid Analysis of Targeted Enzyme Activity in Living Cells
title_sort antagonistic control of genetic circuit performance for rapid analysis of targeted enzyme activity in living cells
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835892/
https://www.ncbi.nlm.nih.gov/pubmed/33511156
http://dx.doi.org/10.3389/fmolb.2020.599878
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