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Metabolic engineering of a reduced-genome strain of Escherichia coli for L-threonine production

BACKGROUND: Deletion of large blocks of nonessential genes that are not needed for metabolic pathways of interest can reduce the production of unwanted by-products, increase genome stability, and streamline metabolism without physiological compromise. Researchers have recently constructed a reduced-...

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Autores principales: Lee, Jun Hyoung, Sung, Bong Hyun, Kim, Mi Sun, Blattner, Frederick R, Yoon, Byoung Hoon, Kim, Jung Hoe, Kim, Sun Chang
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2634754/
https://www.ncbi.nlm.nih.gov/pubmed/19128451
http://dx.doi.org/10.1186/1475-2859-8-2
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author Lee, Jun Hyoung
Sung, Bong Hyun
Kim, Mi Sun
Blattner, Frederick R
Yoon, Byoung Hoon
Kim, Jung Hoe
Kim, Sun Chang
author_facet Lee, Jun Hyoung
Sung, Bong Hyun
Kim, Mi Sun
Blattner, Frederick R
Yoon, Byoung Hoon
Kim, Jung Hoe
Kim, Sun Chang
author_sort Lee, Jun Hyoung
collection PubMed
description BACKGROUND: Deletion of large blocks of nonessential genes that are not needed for metabolic pathways of interest can reduce the production of unwanted by-products, increase genome stability, and streamline metabolism without physiological compromise. Researchers have recently constructed a reduced-genome Escherichia coli strain MDS42 that lacks 14.3% of its chromosome. RESULTS: Here we describe the reengineering of the MDS42 genome to increase the production of the essential amino acid L-threonine. To this end, we over-expressed a feedback-resistant threonine operon (thrA*BC), deleted the genes that encode threonine dehydrogenase (tdh) and threonine transporters (tdcC and sstT), and introduced a mutant threonine exporter (rhtA23) in MDS42. The resulting strain, MDS-205, shows an ~83% increase in L-threonine production when cells are grown by flask fermentation, compared to a wild-type E. coli strain MG1655 engineered with the same threonine-specific modifications described above. And transcriptional analysis revealed the effect of the deletion of non-essential genes on the central metabolism and threonine pathways in MDS-205. CONCLUSION: This result demonstrates that the elimination of genes unnecessary for cell growth can increase the productivity of an industrial strain, most likely by reducing the metabolic burden and improving the metabolic efficiency of cells.
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spelling pubmed-26347542009-02-03 Metabolic engineering of a reduced-genome strain of Escherichia coli for L-threonine production Lee, Jun Hyoung Sung, Bong Hyun Kim, Mi Sun Blattner, Frederick R Yoon, Byoung Hoon Kim, Jung Hoe Kim, Sun Chang Microb Cell Fact Research BACKGROUND: Deletion of large blocks of nonessential genes that are not needed for metabolic pathways of interest can reduce the production of unwanted by-products, increase genome stability, and streamline metabolism without physiological compromise. Researchers have recently constructed a reduced-genome Escherichia coli strain MDS42 that lacks 14.3% of its chromosome. RESULTS: Here we describe the reengineering of the MDS42 genome to increase the production of the essential amino acid L-threonine. To this end, we over-expressed a feedback-resistant threonine operon (thrA*BC), deleted the genes that encode threonine dehydrogenase (tdh) and threonine transporters (tdcC and sstT), and introduced a mutant threonine exporter (rhtA23) in MDS42. The resulting strain, MDS-205, shows an ~83% increase in L-threonine production when cells are grown by flask fermentation, compared to a wild-type E. coli strain MG1655 engineered with the same threonine-specific modifications described above. And transcriptional analysis revealed the effect of the deletion of non-essential genes on the central metabolism and threonine pathways in MDS-205. CONCLUSION: This result demonstrates that the elimination of genes unnecessary for cell growth can increase the productivity of an industrial strain, most likely by reducing the metabolic burden and improving the metabolic efficiency of cells. BioMed Central 2009-01-07 /pmc/articles/PMC2634754/ /pubmed/19128451 http://dx.doi.org/10.1186/1475-2859-8-2 Text en Copyright © 2009 Lee et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Lee, Jun Hyoung
Sung, Bong Hyun
Kim, Mi Sun
Blattner, Frederick R
Yoon, Byoung Hoon
Kim, Jung Hoe
Kim, Sun Chang
Metabolic engineering of a reduced-genome strain of Escherichia coli for L-threonine production
title Metabolic engineering of a reduced-genome strain of Escherichia coli for L-threonine production
title_full Metabolic engineering of a reduced-genome strain of Escherichia coli for L-threonine production
title_fullStr Metabolic engineering of a reduced-genome strain of Escherichia coli for L-threonine production
title_full_unstemmed Metabolic engineering of a reduced-genome strain of Escherichia coli for L-threonine production
title_short Metabolic engineering of a reduced-genome strain of Escherichia coli for L-threonine production
title_sort metabolic engineering of a reduced-genome strain of escherichia coli for l-threonine production
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2634754/
https://www.ncbi.nlm.nih.gov/pubmed/19128451
http://dx.doi.org/10.1186/1475-2859-8-2
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