Advancing protein production with Pichia pastoris

Recombinant DNA technology was initially applied in microbial hosts. The first commercial biopharmaceutical products, such as insulins, growth hormones, and interferons, were produced in bacteria or yeasts. Since then, the market demand has instigated the development of a number of different expression hosts including bacteria, yeasts, fungi, insect cells, mammalian cells and transgenic plants or animals.
Mainly driven by the commercial success of monoclonal antibodies (mAbs), mammalian cells have become the dominant recombinant protein production system for biotherapeutics. However, biologics pipelines are moving from standard mAbs to novel biotherapeutic formats such as small antibody derived formats, non-Ab scaffolds and bioconjugates with less complexity in terms of size and post-translational modification. The changing nature of biotherapeutic pipelines and the increased use of recombinant proteins in non-pharma applications strongly foster the development and optimisation of more cost-efficient microbial expression hosts.
Among these, the approved (FDA, EMA) and safe (GRAS, QPS list) expression host Pichia pastoris (Komagataella phaffii) features cost-efficiency, simple genetic modification and cultivation procedures as well as a powerful secretion capability and subcellular protein processing system that is required for post-translational modifications, which is an advantage over bacterial systems. To address today’s bioprocessing needs and to allow for the exploitation of the growing market potential, access to high-productivity technologies ensuring competitive bioprocess development timelines is necessary.

With manufacturability in mind

VALIDOGEN is addressing these needs by early consideration of production strain and process requirements. The versatility of its UNLOCK PICHIA protein production platform provides the tools and genetic diversity necessary for fine-tuning protein expres­sion.

Key to productivity and development speed is the targeted application of the full toolbox by high-throughput generation and comparison of thousands of combinations of different promoter variants, strain background, helper factors, secretion signals or production regimes.

All aspects of manufacturability from targeted debottlenecking for yield maximisation, to product quality (including glycosylation issues) and regulatory requirements (antibiotic-free strain selection) as well as process safety (methanol-free production) and process economy are considered and inte­grated at the earliest possible stage during strain development. Hence, high-speed indu­strial protein production strain generation is assured paving the way for economically viable processes.

This text was originally published in the European Biotechnology Magazine Spring 2021.