Journal
BIOTECHNOLOGY ADVANCES
Volume 31, Issue 2, Pages 140-153Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biotechadv.2012.09.001
Keywords
Recombinant protein; Biotherapeutics; Microbial cells; Protein folding; Aggregation; Protein production
Categories
Funding
- Federal Ministry of Economy, Family and Youth (BMWFJ)
- Federal Ministry of Traffic, Innovation and Technology (bmvit)
- Styrian Business Promotion Agency SFG
- Standortagentur Tirol and ZIT-Technology Agency of the City of Vienna
- Austrian Research Promotion Agency FFG
- MINECO [IT2009-0021]
- AGAUR [2009SGR-108, 2009SGR-281]
- Xarxa de Referencia en Biotecnologia, XRB
- Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN, Spain)
- VI National RDi Plan
- Instituto de Salud Carlos III
- European Regional Development Fund
- ICREA ACADEMIA award (from ICREA, Catalonia, Spain)
- [ERANET-1B08-007]
- [EUI2008-03610]
- [TEKES 40333/08]
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Both conventional and innovative biomedical approaches require cost-effective protein drugs with high therapeutic potency, improved bioavailability, biocompatibility, stability and pharmacokinetics. The growing longevity of the human population, the increasing incidence and prevalence of age-related diseases and the better comprehension of genetic-linked disorders prompt to develop natural and engineered drugs addressed to fulfill emerging therapeutic demands. Conventional microbial systems have been for long time exploited to produce biotherapeutics, competing with animal cells due to easier operation and lower process costs. However, both biological platforms exhibit important drawbacks (mainly associated to intracellular retention of the product, lack of post-translational modifications and conformational stresses), that cannot be overcome through further strain optimization merely due to physiological constraints. The metabolic diversity among microorganisms offers a spectrum of unconventional hosts, that, being able to bypass some of these weaknesses, are under progressive incorporation into production pipelines. In this review we describe the main biological traits and potentials of emerging bacterial, yeast, fungal and microalgae systems, by comparing selected leading species with well established conventional organisms with a long run in protein drug production. (C) 2012 Elsevier Inc. All rights reserved.
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