ArticleProceedings of the National Academy of Sciences of the United States of America2015
Microfluidic screening and whole-genome sequencing identifies mutations associated with improved protein secretion by yeast.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 196 citations in OpenAlex.
- Iterative evolution ofSynthetic and systems biotechnology · 2026Article
- Engineering Saccharomyces cerevisiae secretory system for recombinant protein production: strategies from signal peptides to protease control.Archives of microbiology · 2026Review
- Droplet microfluidics for biomedical applications: emerging trends and future developments.Microsystems & nanoengineering · 2026Review
- The Power of Yeast.Yeast (Chichester, England) · 2025Review
- YTK Display-and-Secrete: Screening for Optimal Protein Secretion Elements inACS synthetic biology · 2025Article
- Microscopy with microfluidics in microgravity using FlightScope.NPJ microgravity · 2025Article
- Multi-Omics Analysis Reveals Impacts of LincRNA Deletion on Yeast Protein Synthesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Engineering Saccharomyces boulardii for enhanced surface display capacity.Microbial cell factories · 2025Article
- Mining yeast diversity unveils novel targets for improved heterologous laccase production in Saccharomyces cerevisiae.Microbial cell factories · 2025Article
- Modeling for understanding and engineering metabolism.QRB discovery · 2025Article
- Screening microorganisms with robust and stable protein expression and secretion capacity.Protein science : a publication of the Protein Society · 2025Article
- Genome-Wide CRISPRi Screening of Key Genes for Recombinant Protein Expression in Bacillus Subtilis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Directed evolution of material-producing microorganisms.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Coupling thermotolerance and high production of recombinant protein by CYR1Communications biology · 2024Article
- Article
- EngineeringEngineering microbiology · 2024Review
- Genome-wide screen identifies new set of genes for improved heterologous laccase expression in Saccharomyces cerevisiae.Microbial cell factories · 2024Article
- Ultrahigh-throughput screening-assisted in vivo directed evolution for enzyme engineering.Biotechnology for biofuels and bioproducts · 2024Article
- Engineering strategies for enhanced heterologous protein production by Saccharomyces cerevisiae.Microbial cell factories · 2024Review
- Evolution and screening of Trichoderma reesei mutants for secreted protein production at elevated temperature.Journal of industrial microbiology & biotechnology · 2024Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
There is an increasing demand for biotech-based production of recombinant proteins for use as pharmaceuticals in the food and feed industry and in industrial applications. Yeast Saccharomyces cerevisiae is among preferred cell factories for recombinant protein production, and there is increasing interest in improving its protein secretion capacity. Due to the complexity of the secretory machinery in eukaryotic cells, it is difficult to apply rational engineering for construction of improved strains. Here we used high-throughput microfluidics for the screening of yeast libraries, generated by UV mutagenesis. Several screening and sorting rounds resulted in the selection of eight yeast clones with significantly improved secretion of recombinant α-amylase. Efficient secretion was genetically stable in the selected clones. We performed whole-genome sequencing of the eight clones and identified 330 mutations in total. Gene ontology analysis of mutated genes revealed many biological processes, including some that have not been identified before in the context of protein secretion. Mutated genes identified in this study can be potentially used for reverse metabolic engineering, with the objective to construct efficient cell factories for protein secretion. The combined use of microfluidics screening and whole-genome sequencing to map the mutations associated with the improved phenotype can easily be adapted for other products and cell types to identify novel engineering targets, and this approach could broadly facilitate design of novel cell factories.
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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.