ArticleMicrobial cell factories2017
Implications of evolutionary engineering for growth and recombinant protein production in methanol-based growth media in the yeast 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 21 papers.
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Who cites it
21 citing papers in PubMed, 54 citations in OpenAlex.
- Random mutagenesis platform for accelerated genome evolution (RAMPAGE) ofEngineering microbiology · 2026Article
- Living Microbial Drugs.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Review
- Methanol feeding strategies for high-yield production of a collagen-based protein in Komagataella phaffii.Applied microbiology and biotechnology · 2025Article
- Bulk and selective autophagy cooperate to remodel a fungal proteome in response to changing nutrient availability.Cell reports · 2025Article
- Enhanced methanol tolerance and utilization in Pichia pastoris revealed by adaptive laboratory evolution.Journal of biological engineering · 2025Article
- Adaptive laboratory evolution under acetic acid stress enhances the multistress tolerance and ethanol production efficiency of Pichia kudriavzevii from lignocellulosic biomass.Scientific reports · 2023Article
- Deciphering cell wall sensors enabling the construction of robust P. pastoris for single-cell protein production.Biotechnology for biofuels and bioproducts · 2023Article
- Advances in Metabolic Engineering ofJournal of fungi (Basel, Switzerland) · 2023Review
- Economical production of Pichia pastoris single cell protein from methanol at industrial pilot scale.Microbial cell factories · 2023Article
- Methanol-based biomanufacturing of fuels and chemicals using native and synthetic methylotrophs.Synthetic and systems biotechnology · 2023Article
- Improving Methanol Utilization by Reducing Alcohol Oxidase Activity and Adding Co-Substrate of Sodium Citrate inJournal of fungi (Basel, Switzerland) · 2023Article
- Adaptive Laboratory Evolution of Microorganisms: Methodology and Application for Bioproduction.Microorganisms · 2022Review
- Methanol biotransformation toward high-level production of fatty acid derivatives by engineering the industrial yeastProceedings of the National Academy of Sciences of the United States of America · 2022Article
- A streamlined strain engineering workflow with genome-wide screening detects enhanced protein secretion in Komagataella phaffii.Communications biology · 2022Article
- Modular development enables rapid design of media for alternative hosts.Biotechnology and bioengineering · 2022Article
- 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
- Production of bacteriophage-encoded endolysin, LysP11, in Nicotiana benthamiana and its activity as a potent antimicrobial agent against Erysipelothrix rhusiopathiae.Plant cell reports · 2019Article
- The emergence of adaptive laboratory evolution as an efficient tool for biological discovery and industrial biotechnology.Metabolic engineering · 2019Review
- A one-step procedure for immobilising the thermostable carbonic anhydrase (SspCA) on the surface membrane of Escherichia coli.Journal of enzyme inhibition and medicinal chemistry · 2017Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundPichia pastoris is a widely used eukaryotic expression host for recombinant protein production. Adaptive laboratory evolution (ALE) has been applied in a wide range of studies in order to improve strains for biotechnological purposes. In this context, the impact of long-term carbon source adaptation in P. pastoris has not been addressed so far. Thus, we performed a pilot experiment in order to analyze the applicability and potential benefits of ALE towards improved growth and recombinant protein production in P. pastoris.
resultsAdaptation towards growth on methanol was performed in replicate cultures in rich and minimal growth medium for 250 generations. Increased growth rates on these growth media were observed at the population and single clone level. Evolved populations showed various degrees of growth advantages and trade-offs in non-evolutionary growth conditions. Genome resequencing revealed a wide variety of potential genetic targets associated with improved growth performance on methanol-based growth media. Alcohol oxidase represented a mutational hotspot since four out of seven evolved P. pastoris clones harbored mutations in this gene, resulting in decreased Aox activity, despite increased growth rates. Selected clones displayed strain-dependent variations for AOX-promoter based recombinant protein expression yield. One particularly interesting clone showed increased product titers ranging from a 2.5-fold increase in shake flask batch culture to a 1.8-fold increase during fed batch cultivation.
conclusionsOur data indicate a complex correlation of carbon source, growth context and recombinant protein production. While similar experiments have already shown their potential in other biotechnological areas where microbes were evolutionary engineered for improved stress resistance and growth, the current dataset encourages the analysis of the potential of ALE for improved protein production in P. pastoris on a broader scale.
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