Quantitative metabolomics analysis of amino acid metabolism in recombinant Pichia pastoris under different oxygen availability conditions View Full Text


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Article Info

DATE

2012-12

AUTHORS

Marc Carnicer, Angela ten Pierick, Jan van Dam, Joseph J Heijnen, Joan Albiol, Walter van Gulik, Pau Ferrer

ABSTRACT

BACKGROUND: Environmental and intrinsic stress factors can result in the global alteration of yeast physiology, as evidenced by several transcriptional studies. Hypoxia has been shown to have a beneficial effect on the expression of recombinant proteins in Pichia pastoris growing on glucose. Furthermore, transcriptional profiling analyses revealed that oxygen availability was strongly affecting ergosterol biosynthesis, central carbon metabolism and stress responses, in particular the unfolded protein response. To contribute to the better understanding of the effect and interplay of oxygen availability and foreign protein secretion on central metabolism, a first quantitative metabolomic analysis of free amino acids pools in a recombinant P. pastoris strain growing under different oxygen availability conditions has been performed. RESULTS: The values obtained indicate significant variations in the intracellular amino acid pools due to different oxygen availability conditions, showing an overall increase of their size under oxygen limitation. Notably, even while foreign protein productivities were relatively low (about 40-80 μg Fab/g(DCW)·h), recombinant protein production was found to have a limited but significant impact on the intracellular amino acid pools, which were generally decreased in the producing strain compared with the reference strain. However, observed changes in individual amino acids pools were not correlated with their corresponding relative abundance in the recombinant protein sequence, but to the overall cell protein amino acid compositional variations. CONCLUSIONS: Overall, the results obtained, combined with previous transcriptomic and proteomic analyses provide a systematic metabolic fingerprint of the oxygen availability impact on recombinant protein production in P. pastoris. More... »

PAGES

83

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/1475-2859-11-83

    DOI

    http://dx.doi.org/10.1186/1475-2859-11-83

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1011765854

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/22704468


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    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1186/1475-2859-11-83'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/1475-2859-11-83'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/1475-2859-11-83'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/1475-2859-11-83'


     

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