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Updated: Jun 24, 2026

Generic Protocol for Optimization of Heterologous Protein Production Using Automated Microbioreactor Technology
Published on: December 15, 2017
Microbial factories for recombinant pharmaceuticals
Neus Ferrer-Miralles1, Joan Domingo-Espín, José Luis Corchero
1Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain. antoni.villaverde@uab.cat.
Abstract:
Most of the hosts used to produce the 151 recombinant pharmaceuticals so far approved for human use by the Food and Drug Administration (FDA) and/or by the European Medicines Agency (EMEA) are microbial cells, either bacteria or yeast. This fact indicates that despite the diverse bottlenecks and obstacles that microbial systems pose to the efficient production of functional mammalian proteins, namely lack or unconventional post-translational modifications, proteolytic instability, poor solubility and activation of cell stress responses, among others, they represent convenient and powerful tools for recombinant protein production. The entering into the market of a progressively increasing number of protein drugs produced in non-microbial systems has not impaired the development of products obtained in microbial cells, proving the robustness of the microbial set of cellular systems (so far Escherichia coli and Saccharomyces cerevisae) developed for protein drug production. We summarize here the nature, properties and applications of all those pharmaceuticals and the relevant features of the current and potential producing hosts, in a comparative way.
Insights
Microbial systems like bacteria and yeast are robust hosts for producing approved recombinant protein drugs, despite challenges in mammalian protein production. Their continued use highlights their effectiveness in biopharmaceutical manufacturing.
Area of Science:
- Biotechnology and Biopharmaceutical Manufacturing
- Recombinant Protein Production
- Microbial Host Systems
Background:
- 151 recombinant pharmaceuticals approved by FDA/EMEA primarily use microbial hosts (bacteria, yeast).
- Microbial systems present challenges: unconventional post-translational modifications, proteolytic instability, poor solubility, and cell stress responses.
- Despite challenges, microbial systems remain powerful tools for recombinant protein production.
Purpose of the Study:
- To summarize the nature, properties, and applications of approved recombinant pharmaceuticals.
- To comparatively analyze features of current and potential microbial host systems for protein drug production.
Main Methods:
- Review and comparative analysis of existing literature on recombinant pharmaceuticals.
- Evaluation of microbial production systems (Escherichia coli, Saccharomyces cerevisiae) and their performance.
- Assessment of challenges and advantages associated with microbial protein production.
Main Results:
- Microbial systems, particularly E. coli and S. cerevisiae, are extensively used and proven robust for producing approved recombinant drugs.
- The market entry of protein drugs from non-microbial systems has not diminished the development of microbially produced biologics.
- Despite inherent production bottlenecks, microbial systems offer a reliable platform for biopharmaceutical development.
Conclusions:
- Microbial cellular systems are indispensable and robust platforms for the production of a significant number of biopharmaceuticals.
- Continued innovation in microbial strain development and process optimization is crucial for future recombinant protein drug manufacturing.
- Comparative analysis of host systems underscores the enduring value and potential of microbial production platforms.
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