Systems biotechnology for protein production in Pichia pastoris
| Autor: | David A. Peña, Diethard Mattanovich, Richard J. Zahrl, Brigitte Gasser |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Proteomics
0301 basic medicine Systems biology 030106 microbiology Heterologous Computational biology Biology Applied Microbiology and Biotechnology Microbiology Pichia Pichia pastoris Transcriptome 03 medical and health sciences Synthetic biology Metabolomics Systems Biology Genomics General Medicine biology.organism_classification Recombinant Proteins Metabolic Engineering Fermentation Proteome Genome Fungal Genetic Engineering Flux (metabolism) Biotechnology |
| Zdroj: | FEMS Yeast Research. 17 |
| ISSN: | 1567-1364 |
| DOI: | 10.1093/femsyr/fox068 |
| Popis: | The methylotrophic yeast Pichia pastoris (syn. Komagataella spp.) is one of the most important production systems for heterologous proteins. After the first genome sequences were published in 2009, tremendous effort was made to establish systems-level analytical methods. Methylotrophic lifestyle was one of the most thoroughly investigated topics, studied at the levels of transcriptome, proteome and metabolic flux. Also the responses of P. pastoris to environmental stress conditions experienced during high cell density production processes were studied. Metabolomics and flux analysis revealed the plasticity of the cellular metabolism in its adaption to the production of foreign proteins and served as blueprints for subsequent cell engineering and/or process design. The transcriptional response elicited by overexpression of heterologous proteins seems to depend on the nature and complexity of the recombinant product. Based on these data, novel targets for strain engineering could be deduced from transcriptomics and proteomics data mining and effectively enhanced protein secretion. Transcriptional regulation data also served as a valuable resource to identify novel promoters with the desired regulatory characteristics. This review aims to provide a comprehensive overview of systems biology applications in P. pastoris ranging from increased understanding of cell physiology to improving recombinant protein production in this cell factory. |
| Databáze: | OpenAIRE |
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