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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Main Authors: Taliman Afroz, Michelle L Luo, Chase L Beisel
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
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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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