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

Gregory D. Tredwell, Rochelle Aw, Bryn Edwards-Jones, David J. Leak, Jacob G. Bundy

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8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)413-417
Number of pages5
JournalJournal of Industrial Microbiology and Biotechnology
Volume44
Issue number3
Early online date3 Feb 2017
DOIs
Publication statusPublished - Mar 2017

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Keywords

  • Bioprocessing
  • Clonal variation
  • Metabolic footprinting
  • Recombinant protein
  • Unfolded protein response

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