Impact of Residual Inducer on Titratable Expression Systems.
Inducible expression systems are widely employed for the titratable control of gene expression, yet molecules inadvertently present in the growth medium or synthesized by the host cells can alter the response profile of some of these systems. Here, we explored the quantitative impact of these residu...
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Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC4562711?pdf=render |
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author | Taliman Afroz Michelle L Luo Chase L Beisel |
author_facet | Taliman Afroz Michelle L Luo Chase L Beisel |
author_sort | Taliman Afroz |
collection | DOAJ |
description | Inducible expression systems are widely employed for the titratable control of gene expression, yet molecules inadvertently present in the growth medium or synthesized by the host cells can alter the response profile of some of these systems. Here, we explored the quantitative impact of these residual inducers on the apparent response properties of inducible systems. Using a simple mathematical model, we found that the presence of residual inducer shrinks the apparent dynamic range and causes the apparent Hill coefficient to converge to one. We also found that activating systems were more sensitive than repressing systems to the presence of residual inducer and the response parameters were most heavily dependent on the original Hill coefficient. Experimental interrogation of common titratable systems based on an L-arabinose inducible promoter or a thiamine pyrophosphate-repressing riboswitch in Escherichia coli confirmed the predicted trends. We finally found that residual inducer had a distinct effect on "all-or-none" systems, which exhibited increased sensitivity to the added inducer until becoming fully induced. Our findings indicate that residual inducer or repressor alters the quantitative response properties of titratable systems, impacting their utility for scientific discovery and pathway engineering. |
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institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-12-13T01:59:21Z |
publishDate | 2015-01-01 |
publisher | Public Library of Science (PLoS) |
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series | PLoS ONE |
spelling | doaj.art-92e0ae35004741f6a63dbb5e09b102562022-12-22T00:03:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01109e013742110.1371/journal.pone.0137421Impact of Residual Inducer on Titratable Expression Systems.Taliman AfrozMichelle L LuoChase L BeiselInducible expression systems are widely employed for the titratable control of gene expression, yet molecules inadvertently present in the growth medium or synthesized by the host cells can alter the response profile of some of these systems. Here, we explored the quantitative impact of these residual inducers on the apparent response properties of inducible systems. Using a simple mathematical model, we found that the presence of residual inducer shrinks the apparent dynamic range and causes the apparent Hill coefficient to converge to one. We also found that activating systems were more sensitive than repressing systems to the presence of residual inducer and the response parameters were most heavily dependent on the original Hill coefficient. Experimental interrogation of common titratable systems based on an L-arabinose inducible promoter or a thiamine pyrophosphate-repressing riboswitch in Escherichia coli confirmed the predicted trends. We finally found that residual inducer had a distinct effect on "all-or-none" systems, which exhibited increased sensitivity to the added inducer until becoming fully induced. Our findings indicate that residual inducer or repressor alters the quantitative response properties of titratable systems, impacting their utility for scientific discovery and pathway engineering.http://europepmc.org/articles/PMC4562711?pdf=render |
spellingShingle | Taliman Afroz Michelle L Luo Chase L Beisel Impact of Residual Inducer on Titratable Expression Systems. PLoS ONE |
title | Impact of Residual Inducer on Titratable Expression Systems. |
title_full | Impact of Residual Inducer on Titratable Expression Systems. |
title_fullStr | Impact of Residual Inducer on Titratable Expression Systems. |
title_full_unstemmed | Impact of Residual Inducer on Titratable Expression Systems. |
title_short | Impact of Residual Inducer on Titratable Expression Systems. |
title_sort | impact of residual inducer on titratable expression systems |
url | http://europepmc.org/articles/PMC4562711?pdf=render |
work_keys_str_mv | AT talimanafroz impactofresidualinducerontitratableexpressionsystems AT michellelluo impactofresidualinducerontitratableexpressionsystems AT chaselbeisel impactofresidualinducerontitratableexpressionsystems |