ArticleApplied microbiology and biotechnology2013
Investigating the physiological response of Pichia (Komagataella) pastoris GS115 to the heterologous expression of misfolded proteins using chemostat cultures.
Article in Applied microbiology and biotechnology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
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- Secretory helpers for enhanced production of heterologous proteins inBiotechnology reports (Amsterdam, Netherlands) · 2021Article
- Global transcriptome profiling reveals genes responding to overproduction of a small secretory, a high cysteine- and a high glycosylation-bearing protein inBiotechnology reports (Amsterdam, Netherlands) · 2021Article
- Engineering of the unfolded protein response pathway in Pichia pastoris: enhancing production of secreted recombinant proteins.Applied microbiology and biotechnology · 2021Review
- Development of a dual specific growth rate-based fed-batch process for production of recombinant human granulocyte colony-stimulating factor in Pichia pastoris.Bioprocess and biosystems engineering · 2021Article
- Production and secretion dynamics of prokaryotic Penicillin G acylase in Pichia pastoris.Applied microbiology and biotechnology · 2020Article
- Continuous Cultivation as a Tool Toward the Rational Bioprocess Development WithFrontiers in bioengineering and biotechnology · 2020Review
- Transcriptomic Analysis ofFrontiers in microbiology · 2020Article
- Yeast Systems Biology: The Continuing Challenge of Eukaryotic Complexity.Methods in molecular biology (Clifton, N.J.) · 2019Article
- Single-Cell Approach to Monitor the Unfolded Protein Response During Biotechnological Processes WithFrontiers in microbiology · 2019Article
- Process development for the continuous production of heterologous proteins by the industrial yeast, Komagataella phaffii.Biotechnology and bioengineering · 2018Article
- Fate of the UPR marker protein Kar2/Bip and autophagic processes in fed-batch cultures of secretory insulin precursor producing Pichia pastoris.Microbial cell factories · 2018Article
- Improved recombinant protein production in Arabidopsis thaliana.Plant signaling & behavior · 2018Article
- Identification of novel factors enhancing recombinant protein production in multi-copy Komagataella phaffii based on transcriptomic analysis of overexpression effects.Scientific reports · 2017Article
- CamOptimus: a tool for exploiting complex adaptive evolution to optimize experiments and processes in biotechnology.Microbiology (Reading, England) · 2017Article
- The effect of hypoxia on the lipidome of recombinant Pichia pastoris.Microbial cell factories · 2017Article
- Effects of glycerol supply and specific growth rate on methanol-free production of CALB by P. pastoris: functional characterisation of a novel promoter.Applied microbiology and biotechnology · 2017Article
- Increased dosage of AOX1 promoter-regulated expression cassettes leads to transcription attenuation of the methanol metabolism in Pichia pastoris.Scientific reports · 2017Article
- Rapid screening of cellular stress responses in recombinant Pichia pastoris strains using metabolite profiling.Journal of industrial microbiology & biotechnology · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Pichia pastoris is widely used as a host system for heterologous protein expression in both academia and industry. Production is typically accomplished by a fed-batch induction process that is known to have negative impacts on cell physiology that impose limits on both protein yields and quality. We have analysed recombinant protein production in chemostat cultures to understand the physiological responses associated with methanol-induced production of two human lysozyme variants with different degrees of misfolding by P. pastoris. Confounding variables associated with nutrient stress or growth-rate are minimised during steady-state growth in chemostats. Comparison of transcriptome-level data obtained during the non-inducing and inducing steady states identified changes in expression of only about 1 % of the genome during production of either an amyloidogenic human lysozyme variant prone to intracellular aggregation (I56T) or a misfolded but secretable variant (T70N), indicating near-complete acclimation to their production. A marked, but temporary, stress response involving both the unfolded protein response (UPR) and ER-associated degradation pathway was observed during the transient between steady states, particularly following induction of the T70N variant synthesis, and was accompanied by changes in expression of around 50 antisense transcripts. The results suggest that optimal heterologous protein production could best be achieved by a continuous process that minimises the number of methanol-induced transients experienced by the cultures. The processing of HAC1 mRNA required for the UPR was found to be constitutive in the culture conditions used, even in the absence of recombinant protein induction.
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Registered trials
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