Improving heterologous membrane protein production in Escherichia coli by combining transcriptional tuning and codon usage algorithms.

High-level, recombinant production of membrane-integrated proteins in Escherichia coli is extremely relevant for many purposes, but has also been proven challenging. Here we study a combination of transcriptional fine-tuning in E. coli LEMO21(DE3) with different codon usage algorithms for heterologo...

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Main Authors: Nico J Claassens, Melvin F Siliakus, Sebastiaan K Spaans, Sjoerd C A Creutzburg, Bart Nijsse, Peter J Schaap, Tessa E F Quax, John van der Oost
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0184355&type=printable
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author Nico J Claassens
Melvin F Siliakus
Sebastiaan K Spaans
Sjoerd C A Creutzburg
Bart Nijsse
Peter J Schaap
Tessa E F Quax
John van der Oost
author_facet Nico J Claassens
Melvin F Siliakus
Sebastiaan K Spaans
Sjoerd C A Creutzburg
Bart Nijsse
Peter J Schaap
Tessa E F Quax
John van der Oost
author_sort Nico J Claassens
collection DOAJ
description High-level, recombinant production of membrane-integrated proteins in Escherichia coli is extremely relevant for many purposes, but has also been proven challenging. Here we study a combination of transcriptional fine-tuning in E. coli LEMO21(DE3) with different codon usage algorithms for heterologous production of membrane proteins. The overexpression of 6 different membrane proteins is compared for the wild-type gene codon usage variant, a commercially codon-optimized variant, and a codon-harmonized variant. We show that transcriptional fine-tuning plays a major role in improving the production of all tested proteins. Moreover, different codon usage variants significantly improved production of some of the tested proteins. However, not a single algorithm performed consistently best for the membrane-integrated production of the 6 tested proteins. In conclusion, for improving heterologous membrane protein production in E. coli, the major effect is accomplished by transcriptional tuning. In addition, further improvements may be realized by attempting different codon usage variants, such as codon harmonized variants, which can now be easily generated through our online Codon Harmonizer tool.
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issn 1932-6203
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publisher Public Library of Science (PLoS)
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spelling doaj-art-c963d8bea3bf4f098f799476ca6e07022025-08-20T02:04:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01129e018435510.1371/journal.pone.0184355Improving heterologous membrane protein production in Escherichia coli by combining transcriptional tuning and codon usage algorithms.Nico J ClaassensMelvin F SiliakusSebastiaan K SpaansSjoerd C A CreutzburgBart NijssePeter J SchaapTessa E F QuaxJohn van der OostHigh-level, recombinant production of membrane-integrated proteins in Escherichia coli is extremely relevant for many purposes, but has also been proven challenging. Here we study a combination of transcriptional fine-tuning in E. coli LEMO21(DE3) with different codon usage algorithms for heterologous production of membrane proteins. The overexpression of 6 different membrane proteins is compared for the wild-type gene codon usage variant, a commercially codon-optimized variant, and a codon-harmonized variant. We show that transcriptional fine-tuning plays a major role in improving the production of all tested proteins. Moreover, different codon usage variants significantly improved production of some of the tested proteins. However, not a single algorithm performed consistently best for the membrane-integrated production of the 6 tested proteins. In conclusion, for improving heterologous membrane protein production in E. coli, the major effect is accomplished by transcriptional tuning. In addition, further improvements may be realized by attempting different codon usage variants, such as codon harmonized variants, which can now be easily generated through our online Codon Harmonizer tool.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0184355&type=printable
spellingShingle Nico J Claassens
Melvin F Siliakus
Sebastiaan K Spaans
Sjoerd C A Creutzburg
Bart Nijsse
Peter J Schaap
Tessa E F Quax
John van der Oost
Improving heterologous membrane protein production in Escherichia coli by combining transcriptional tuning and codon usage algorithms.
PLoS ONE
title Improving heterologous membrane protein production in Escherichia coli by combining transcriptional tuning and codon usage algorithms.
title_full Improving heterologous membrane protein production in Escherichia coli by combining transcriptional tuning and codon usage algorithms.
title_fullStr Improving heterologous membrane protein production in Escherichia coli by combining transcriptional tuning and codon usage algorithms.
title_full_unstemmed Improving heterologous membrane protein production in Escherichia coli by combining transcriptional tuning and codon usage algorithms.
title_short Improving heterologous membrane protein production in Escherichia coli by combining transcriptional tuning and codon usage algorithms.
title_sort improving heterologous membrane protein production in escherichia coli by combining transcriptional tuning and codon usage algorithms
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0184355&type=printable
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