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Rapid screening of cellular stress responses in recombinant Pichia pastoris strains using metabolite profiling

Heterologous protein production in the yeast Pichia pastoris can be limited by biological responses to high expression levels; the unfolded protein response (UPR) is a key determinant of the success of protein production in this organism. Here, we used untargeted NMR metabolic profiling (metabolomic...

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Autores principales: Tredwell, Gregory D., Aw, Rochelle, Edwards-Jones, Bryn, Leak, David J., Bundy, Jacob G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5329079/
https://www.ncbi.nlm.nih.gov/pubmed/28160205
http://dx.doi.org/10.1007/s10295-017-1904-5
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author Tredwell, Gregory D.
Aw, Rochelle
Edwards-Jones, Bryn
Leak, David J.
Bundy, Jacob G.
author_facet Tredwell, Gregory D.
Aw, Rochelle
Edwards-Jones, Bryn
Leak, David J.
Bundy, Jacob G.
author_sort Tredwell, Gregory D.
collection PubMed
description Heterologous protein production in the yeast Pichia pastoris can be limited by biological responses to high expression levels; the unfolded protein response (UPR) is a key determinant of the success of protein production in this organism. Here, we used untargeted NMR metabolic profiling (metabolomics) of a number of different recombinant strains, carried out in a miniaturized format suitable for screening-level experiments. We identified a number of metabolites (from both cell extracts and supernatants) which correlated well with UPR-relevant gene transcripts, and so could be potential biomarkers for future high-throughput screening of large numbers of P. pastoris clones. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10295-017-1904-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-53290792017-03-13 Rapid screening of cellular stress responses in recombinant Pichia pastoris strains using metabolite profiling Tredwell, Gregory D. Aw, Rochelle Edwards-Jones, Bryn Leak, David J. Bundy, Jacob G. J Ind Microbiol Biotechnol Fermentation, Cell Culture and Bioengineering - Short Communication Heterologous protein production in the yeast Pichia pastoris can be limited by biological responses to high expression levels; the unfolded protein response (UPR) is a key determinant of the success of protein production in this organism. Here, we used untargeted NMR metabolic profiling (metabolomics) of a number of different recombinant strains, carried out in a miniaturized format suitable for screening-level experiments. We identified a number of metabolites (from both cell extracts and supernatants) which correlated well with UPR-relevant gene transcripts, and so could be potential biomarkers for future high-throughput screening of large numbers of P. pastoris clones. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10295-017-1904-5) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2017-02-03 2017 /pmc/articles/PMC5329079/ /pubmed/28160205 http://dx.doi.org/10.1007/s10295-017-1904-5 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Fermentation, Cell Culture and Bioengineering - Short Communication
Tredwell, Gregory D.
Aw, Rochelle
Edwards-Jones, Bryn
Leak, David J.
Bundy, Jacob G.
Rapid screening of cellular stress responses in recombinant Pichia pastoris strains using metabolite profiling
title Rapid screening of cellular stress responses in recombinant Pichia pastoris strains using metabolite profiling
title_full Rapid screening of cellular stress responses in recombinant Pichia pastoris strains using metabolite profiling
title_fullStr Rapid screening of cellular stress responses in recombinant Pichia pastoris strains using metabolite profiling
title_full_unstemmed Rapid screening of cellular stress responses in recombinant Pichia pastoris strains using metabolite profiling
title_short Rapid screening of cellular stress responses in recombinant Pichia pastoris strains using metabolite profiling
title_sort rapid screening of cellular stress responses in recombinant pichia pastoris strains using metabolite profiling
topic Fermentation, Cell Culture and Bioengineering - Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5329079/
https://www.ncbi.nlm.nih.gov/pubmed/28160205
http://dx.doi.org/10.1007/s10295-017-1904-5
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