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Efficient protein production by yeast requires global tuning of metabolism
KTH, Centres, Science for Life Laboratory, SciLifeLab.
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2017 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, no 1, article id 1131Article in journal (Refereed) Published
Abstract [en]

The biotech industry relies on cell factories for production of pharmaceutical proteins, of which several are among the top-selling medicines. There is, therefore, considerable interest in improving the efficiency of protein production by cell factories. Protein secretion involves numerous intracellular processes with many underlying mechanisms still remaining unclear. Here, we use RNA-seq to study the genome-wide transcriptional response to protein secretion in mutant yeast strains. We find that many cellular processes have to be attuned to support efficient protein secretion. In particular, altered energy metabolism resulting in reduced respiration and increased fermentation, as well as balancing of amino-acid biosynthesis and reduced thiamine biosynthesis seem to be particularly important. We confirm our findings by inverse engineering and physiological characterization and show that by tuning metabolism cells are able to efficiently secrete recombinant proteins. Our findings provide increased understanding of which cellular regulations and pathways are associated with efficient protein secretion.

Place, publisher, year, edition, pages
Nature Publishing Group , 2017. Vol. 8, no 1, article id 1131
Keyword [en]
amylase, carbohydrate, protein, thiamine, biological production, biotechnology, efficiency measurement, genetic engineering, metabolism, yeast, AAC3 gene, amino acid synthesis, amylase release, ANB1 gene, Article, bacterium culture, carbohydrate metabolism, CYC7 gene, DAN1 gene, endoplasmic reticulum stress, energy metabolism, fermentation, fungal gene, FUR1 gene, genome-wide association study, MSS11 gene, nonhuman, PHO12 gene, PHO84 gene, PHO89 gene, protein metabolism, protein secretion, reporter gene, RNA sequence, SNF2 gene, SPL2 gene, SUT1 gene, SWI4 gene, TEC1 gene, TIR3 gene
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:kth:diva-227126DOI: 10.1038/s41467-017-00999-2Scopus ID: 2-s2.0-85032290095OAI: oai:DiVA.org:kth-227126DiVA, id: diva2:1204552
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QC 20180508

Available from: 2018-05-08 Created: 2018-05-08 Last updated: 2018-05-08Bibliographically approved

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Hallström, Björn M.Nielsen, Jens

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Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)Biochemistry and Molecular Biology

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