ArticlePloS one2012
Systematic single-cell analysis of Pichia pastoris reveals secretory capacity limits productivity.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Deletion of low-essentiality, secretion-associated genes enhances recombinant protein production in Komagataella phaffii.Microbial cell factories · 2026Article
- Systematic perturbation of cultures of K. phaffii by carbon co-feeding show gene signatures associated with production of recombinant proteins.Microbial cell factories · 2026Article
- The effect of the bgs13 mutation on the structure of the reporter protein beta-lactoglobulin: Influence on folding and aggregation in Pichia pastoris.Protein expression and purification · 2023Article
- Maximizing protein production by keeping cells at optimal secretory stress levels using real-time control approaches.Nature communications · 2023Article
- Microfluidic Single-Cell Analytics.Advances in biochemical engineering/biotechnology · 2022Article
- Platforms for Production of Protein-Based Vaccines: From Classical to Next-Generation Strategies.Biomolecules · 2021Review
- Engineering of the unfolded protein response pathway in Pichia pastoris: enhancing production of secreted recombinant proteins.Applied microbiology and biotechnology · 2021Review
- Translational landscape and protein biogenesis demands of the early secretory pathway in Komagataella phaffii.Microbial cell factories · 2021Article
- Production and secretion dynamics of prokaryotic Penicillin G acylase in Pichia pastoris.Applied microbiology and biotechnology · 2020Article
- Mining Data From Plasma Cell Differentiation Identified Novel Genes for Engineering of a Yeast Antibody Factory.Frontiers in bioengineering and biotechnology · 2020Article
- Contextualized genome-scale model unveils high-order metabolic effects of the specific growth rate and oxygenation level in recombinantMetabolic engineering communications · 2019Article
- Single-Cell Approach to Monitor the Unfolded Protein Response During Biotechnological Processes WithFrontiers in microbiology · 2019Article
- Effect of Plasmid Design and Type of Integration Event on Recombinant Protein Expression in Pichia pastoris.Applied and environmental microbiology · 2018Article
- Expressing anti-HIV VRC01 antibody using the murine IgG1 secretion signal in Pichia pastoris.AMB Express · 2017Article
- Beyond the bulk: disclosing the life of single microbial cells.FEMS microbiology reviews · 2017Review
- 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
- Rapid screening of cellular stress responses in recombinant Pichia pastoris strains using metabolite profiling.Journal of industrial microbiology & biotechnology · 2017Article
- Systematic Optimization of Protein Secretory Pathways inFrontiers in microbiology · 2017Article
- Production of Chimeric Acidic α-Amylase by the RecombinantFrontiers in microbiology · 2017Article
- Characterization of a panARS-based episomal vector in the methylotrophic yeast Pichia pastoris for recombinant protein production and synthetic biology applications.Microbial cell factories · 2016Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Biopharmaceuticals represent the fastest growing sector of the global pharmaceutical industry. Cost-efficient production of these biologic drugs requires a robust host organism for generating high titers of protein during fermentation. Understanding key cellular processes that limit protein production and secretion is, therefore, essential for rational strain engineering. Here, with single-cell resolution, we systematically analysed the productivity of a series of Pichia pastoris strains that produce different proteins both constitutively and inducibly. We characterized each strain by qPCR, RT-qPCR, microengraving, and imaging cytometry. We then developed a simple mathematical model describing the flux of folded protein through the ER. This combination of single-cell measurements and computational modelling shows that protein trafficking through the secretory machinery is often the rate-limiting step in single-cell production, and strategies to enhance the overall capacity of protein secretion within hosts for the production of heterologous proteins may improve productivity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.