ArticleMicrobial cell factories2017
The effect of hypoxia on the lipidome of recombinant Pichia pastoris.
Article in Microbial cell factories, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 46 citations in OpenAlex.
- Impact of Oxygen Availability on the Organelle-Specific Redox Potentials and Stress in Recombinant Protein Producing Komagataella phaffii.Microbial biotechnology · 2025Article
- Impact of cell wall polysaccharide modifications on the performance of Pichia pastoris: novel mutants with enhanced fitness and functionality for bioproduction applications.Microbial cell factories · 2024Article
- Protein production dynamics and physiological adaptation of recombinant Komagataella phaffii at near-zero growth rates.Microbial cell factories · 2024Article
- Synergic kinetic and physiological control to improve the efficiency of Komagataella phaffii recombinant protein production bioprocesses.Microbial biotechnology · 2024Article
- Human Sterols Are Overproduced, Stored and Excreted in Yeasts.International journal of molecular sciences · 2024Article
- Alternative PCR-Based Approaches for Generation ofMicroorganisms · 2023Article
- Production, purification, and characterization of recombinant rabies virus glycoprotein expressed in PichiaPink™ yeast.Biotechnology reports (Amsterdam, Netherlands) · 2022Article
- Innovative Bioprocess Strategies Combining Physiological Control and Strain Engineering ofFrontiers in bioengineering and biotechnology · 2022Article
- Engineering of the unfolded protein response pathway in Pichia pastoris: enhancing production of secreted recombinant proteins.Applied microbiology and biotechnology · 2021Review
- Enhanced Recombinant Protein Production Under Special Environmental Stress.Frontiers in microbiology · 2021Review
- Redox Engineering by Ectopic Overexpression of NADH Kinase in Recombinant Pichia pastoris (Applied and environmental microbiology · 2020Article
- Rationale-based selection of optimal operating strategies and gene dosage impact on recombinant protein production in Komagataella phaffii (Pichia pastoris).Microbial biotechnology · 2020Article
- Continuous Cultivation as a Tool Toward the Rational Bioprocess Development WithFrontiers in bioengineering and biotechnology · 2020Review
- Contextualized genome-scale model unveils high-order metabolic effects of the specific growth rate and oxygenation level in recombinantMetabolic engineering communications · 2019Article
- Whole-cell (+)-ambrein production in the yeastMetabolic engineering communications · 2018Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCultivation of recombinant Pichia pastoris (Komagataella sp.) under hypoxic conditions has a strong positive effect on specific productivity when the glycolytic GAP promoter is used for recombinant protein expression, mainly due to upregulation of glycolytic conditions. In addition, transcriptomic analyses of hypoxic P. pastoris pointed out important regulation of lipid metabolism and unfolded protein response (UPR). Notably, UPR that plays a role in the regulation of lipid metabolism, amino acid metabolism and protein secretion, was found to be upregulated under hypoxia.
resultsTo improve our understanding of the interplay between lipid metabolism, UPR and protein secretion, the lipidome of a P. pastoris strain producing an antibody fragment was studied under hypoxic conditions. Furthermore, lipid composition analyses were combined with previously available transcriptomic datasets to further understand the impact of hypoxia on lipid metabolism. Chemostat cultures operated under glucose-limiting conditions under normoxic and hypoxic conditions were analyzed in terms of intra/extracellular product distribution and lipid composition. Integrated analysis of lipidome and transcriptome datasets allowed us to demonstrate an important remodeling of the lipid metabolism under limited oxygen availability. Additionally, cells with reduced amounts of ergosterol through fluconazole treatment were also included in the study to observe the impact on protein secretion and its lipid composition.
conclusionsOur results show that cells adjust their membrane composition in response to oxygen limitation mainly by changing their sterol and sphingolipid composition. Although fluconazole treatment results a different lipidome profile than hypoxia, both conditions result in higher recombinant protein secretion levels.
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