Biotechnological production processes are usually caught between the required high complexity of the target proteins and the most cost-effective and simple handling possible. Pichia pastoris could now combine these properties.
Most medicinally active recombinant proteins and technical enzymes are produced using E. coli, filamentous fungi and cell cultures such as CHO (Chinese hamster ovary) cells. Well-known examples are erythropoietin, produced using CHO cells, for the treatment of anaemia or G-CSF (granulocyte colony stimulating factor), produced using E. coli or CHO cells, to reduce the risk of infection during chemotherapy. The production processes have been known and proven for decades. With all these host organisms, however, there is an area of tension, because the higher the required complexity of the target proteins, the more similar or even identical they have to be to the human protein, the more likely it is that expensive and complex cell lines will be used.
The yeast strain Komagataella phaffii (known as Pichia pastoris) is now considered the second choice in many laboratories. However, P. pastoris as a unicellular organism (eukaryote) has great potential, as this yeast could in principle combine the simplicity of E. coli, the cost-effective efficient production by filamentous fungi and the ability for typical complex post-translation processes of mammalian cell lines, such as CHO cells. Inspired by the research successes on the yeast model S. cerevisiae and by a combination with the specific advantageous properties of P. pastoris, this CD Laboratory explores basic biological mechanisms of highly efficient P. pastoris cell lines. In this way, the use of P. pastoris as a first-choice expression system will be achieved.
To this end, the mechanistic principles in existing and newly emerging P. pastoris expression strains must be elucidated. Furthermore, a new generation of simple and stable DNA vectors based on new DNA elements will be designed and constructed. This should allow cloning work, the production of gene libraries and reliable scaling without major method or system changes.
This research concept will bring previously unknown cellular mechanisms to light, which in the long term will make the production and application of molecular tools in research and in the manufacturing industry more efficient and enable the production of cost-effective therapeutics and enzymes for new environmentally friendly chemical processes.
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