Rapid screening of cellular stress responses in recombinant Pichia pastoris strains using metabolite profiling
Date
2017
Authors
Tredwell, Greg
Aw, Rochelle
Edwards-Jones, Bryn
Leak, David J
Bundy, Jacob G
Journal Title
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Volume Title
Publisher
Springer Verlag
Abstract
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.
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Keywords
Metabolic footprinting, Unfolded protein response, Clonal variation, Bioprocessing, Recombinant protein
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Source
Journal of Industrial Microbiology and Biotechnology
Type
Journal article
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Access Statement
Open Access
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Creative Commons Attribution 4.0 International License
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