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Pathway optimization by re-design of untranslated regions for L-tyrosine production in Escherichia coli

L-tyrosine is a commercially important compound in the food, pharmaceutical, chemical, and cosmetic industries. Although several attempts have been made to improve L-tyrosine production, translation-level expression control and carbon flux rebalancing around phosphoenolpyruvate (PEP) node still rema...

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Autores principales: Cheol Kim, Seong, Eun Min, Byung, Gyu Hwang, Hyun, Woo Seo, Sang, Yeol Jung, Gyoo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4561953/
https://www.ncbi.nlm.nih.gov/pubmed/26346938
http://dx.doi.org/10.1038/srep13853
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author Cheol Kim, Seong
Eun Min, Byung
Gyu Hwang, Hyun
Woo Seo, Sang
Yeol Jung, Gyoo
author_facet Cheol Kim, Seong
Eun Min, Byung
Gyu Hwang, Hyun
Woo Seo, Sang
Yeol Jung, Gyoo
author_sort Cheol Kim, Seong
collection PubMed
description L-tyrosine is a commercially important compound in the food, pharmaceutical, chemical, and cosmetic industries. Although several attempts have been made to improve L-tyrosine production, translation-level expression control and carbon flux rebalancing around phosphoenolpyruvate (PEP) node still remain to be achieved for optimizing the pathway. Here, we demonstrate pathway optimization by altering gene expression levels for L-tyrosine production in Escherichia coli. To optimize the L-tyrosine biosynthetic pathway, a synthetic constitutive promoter and a synthetic 5′-untranslated region (5′-UTR) were introduced for each gene of interest to allow for control at both transcription and translation levels. Carbon flux rebalancing was achieved by controlling the expression level of PEP synthetase using UTR Designer. The L-tyrosine productivity of the engineered E. coli strain was increased through pathway optimization resulting in 3.0 g/L of L-tyrosine titer, 0.0354 g L-tyrosine/h/g DCW of productivity, and 0.102 g L-tyrosine/g glucose yield. Thus, this work demonstrates that pathway optimization by 5′-UTR redesign is an effective strategy for the development of efficient L-tyrosine-producing bacteria.
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spelling pubmed-45619532015-09-15 Pathway optimization by re-design of untranslated regions for L-tyrosine production in Escherichia coli Cheol Kim, Seong Eun Min, Byung Gyu Hwang, Hyun Woo Seo, Sang Yeol Jung, Gyoo Sci Rep Article L-tyrosine is a commercially important compound in the food, pharmaceutical, chemical, and cosmetic industries. Although several attempts have been made to improve L-tyrosine production, translation-level expression control and carbon flux rebalancing around phosphoenolpyruvate (PEP) node still remain to be achieved for optimizing the pathway. Here, we demonstrate pathway optimization by altering gene expression levels for L-tyrosine production in Escherichia coli. To optimize the L-tyrosine biosynthetic pathway, a synthetic constitutive promoter and a synthetic 5′-untranslated region (5′-UTR) were introduced for each gene of interest to allow for control at both transcription and translation levels. Carbon flux rebalancing was achieved by controlling the expression level of PEP synthetase using UTR Designer. The L-tyrosine productivity of the engineered E. coli strain was increased through pathway optimization resulting in 3.0 g/L of L-tyrosine titer, 0.0354 g L-tyrosine/h/g DCW of productivity, and 0.102 g L-tyrosine/g glucose yield. Thus, this work demonstrates that pathway optimization by 5′-UTR redesign is an effective strategy for the development of efficient L-tyrosine-producing bacteria. Nature Publishing Group 2015-09-08 /pmc/articles/PMC4561953/ /pubmed/26346938 http://dx.doi.org/10.1038/srep13853 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Cheol Kim, Seong
Eun Min, Byung
Gyu Hwang, Hyun
Woo Seo, Sang
Yeol Jung, Gyoo
Pathway optimization by re-design of untranslated regions for L-tyrosine production in Escherichia coli
title Pathway optimization by re-design of untranslated regions for L-tyrosine production in Escherichia coli
title_full Pathway optimization by re-design of untranslated regions for L-tyrosine production in Escherichia coli
title_fullStr Pathway optimization by re-design of untranslated regions for L-tyrosine production in Escherichia coli
title_full_unstemmed Pathway optimization by re-design of untranslated regions for L-tyrosine production in Escherichia coli
title_short Pathway optimization by re-design of untranslated regions for L-tyrosine production in Escherichia coli
title_sort pathway optimization by re-design of untranslated regions for l-tyrosine production in escherichia coli
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4561953/
https://www.ncbi.nlm.nih.gov/pubmed/26346938
http://dx.doi.org/10.1038/srep13853
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