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Restoration of fitness lost due to dysregulation of the pyruvate dehydrogenase complex is triggered by ribosomal binding site modifications

Pyruvate dehydrogenase complex (PDC) functions as the main determinant of the respiro-fermentative balance because it converts pyruvate to acetyl-coenzyme A (CoA), which then enters the TCA (tricarboxylic acid cycle). PDC is repressed by the pyruvate dehydrogenase complex regulator (PdhR) in Escheri...

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Autores principales: Anand, Amitesh, Olson, Connor A., Sastry, Anand V., Patel, Arjun, Szubin, Richard, Yang, Laurence, Feist, Adam M., Palsson, Bernhard O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489512/
https://www.ncbi.nlm.nih.gov/pubmed/33826886
http://dx.doi.org/10.1016/j.celrep.2021.108961
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author Anand, Amitesh
Olson, Connor A.
Sastry, Anand V.
Patel, Arjun
Szubin, Richard
Yang, Laurence
Feist, Adam M.
Palsson, Bernhard O.
author_facet Anand, Amitesh
Olson, Connor A.
Sastry, Anand V.
Patel, Arjun
Szubin, Richard
Yang, Laurence
Feist, Adam M.
Palsson, Bernhard O.
author_sort Anand, Amitesh
collection PubMed
description Pyruvate dehydrogenase complex (PDC) functions as the main determinant of the respiro-fermentative balance because it converts pyruvate to acetyl-coenzyme A (CoA), which then enters the TCA (tricarboxylic acid cycle). PDC is repressed by the pyruvate dehydrogenase complex regulator (PdhR) in Escherichia coli. The deletion of the pdhR gene compromises fitness in aerobic environments. We evolve the E. coli pdhR deletion strain to examine its achievable growth rate and the underlying adaptive strategies. We find that (1) optimal proteome allocation to PDC is critical in achieving optimal growth rate; (2) expression of PDC in evolved strains is reduced through mutations in the Shine-Dalgarno sequence; (3) rewiring of the TCA flux and increased reactive oxygen species (ROS) defense occur in the evolved strains; and (4) the evolved strains adapt to an efficient biomass yield. Together, these results show how adaptation can find alternative regulatory mechanisms for a key cellular process if the primary regulatory mode fails.
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spelling pubmed-84895122021-10-04 Restoration of fitness lost due to dysregulation of the pyruvate dehydrogenase complex is triggered by ribosomal binding site modifications Anand, Amitesh Olson, Connor A. Sastry, Anand V. Patel, Arjun Szubin, Richard Yang, Laurence Feist, Adam M. Palsson, Bernhard O. Cell Rep Article Pyruvate dehydrogenase complex (PDC) functions as the main determinant of the respiro-fermentative balance because it converts pyruvate to acetyl-coenzyme A (CoA), which then enters the TCA (tricarboxylic acid cycle). PDC is repressed by the pyruvate dehydrogenase complex regulator (PdhR) in Escherichia coli. The deletion of the pdhR gene compromises fitness in aerobic environments. We evolve the E. coli pdhR deletion strain to examine its achievable growth rate and the underlying adaptive strategies. We find that (1) optimal proteome allocation to PDC is critical in achieving optimal growth rate; (2) expression of PDC in evolved strains is reduced through mutations in the Shine-Dalgarno sequence; (3) rewiring of the TCA flux and increased reactive oxygen species (ROS) defense occur in the evolved strains; and (4) the evolved strains adapt to an efficient biomass yield. Together, these results show how adaptation can find alternative regulatory mechanisms for a key cellular process if the primary regulatory mode fails. 2021-04-06 /pmc/articles/PMC8489512/ /pubmed/33826886 http://dx.doi.org/10.1016/j.celrep.2021.108961 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
Anand, Amitesh
Olson, Connor A.
Sastry, Anand V.
Patel, Arjun
Szubin, Richard
Yang, Laurence
Feist, Adam M.
Palsson, Bernhard O.
Restoration of fitness lost due to dysregulation of the pyruvate dehydrogenase complex is triggered by ribosomal binding site modifications
title Restoration of fitness lost due to dysregulation of the pyruvate dehydrogenase complex is triggered by ribosomal binding site modifications
title_full Restoration of fitness lost due to dysregulation of the pyruvate dehydrogenase complex is triggered by ribosomal binding site modifications
title_fullStr Restoration of fitness lost due to dysregulation of the pyruvate dehydrogenase complex is triggered by ribosomal binding site modifications
title_full_unstemmed Restoration of fitness lost due to dysregulation of the pyruvate dehydrogenase complex is triggered by ribosomal binding site modifications
title_short Restoration of fitness lost due to dysregulation of the pyruvate dehydrogenase complex is triggered by ribosomal binding site modifications
title_sort restoration of fitness lost due to dysregulation of the pyruvate dehydrogenase complex is triggered by ribosomal binding site modifications
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489512/
https://www.ncbi.nlm.nih.gov/pubmed/33826886
http://dx.doi.org/10.1016/j.celrep.2021.108961
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