Unconventional microbial systems for the cost-efficient production of high-quality protein therapeutics

José Luis Corchero, Brigitte Gasser, David Resina, Wesley Smith, Ermenegilda Parrilli, Felícitaz Vázquez, Ibane Abasolo, Maria Giuliani, Jussi Jäntti, Pau Ferrer, Markku Saloheimo, Diethard Mattanovich, Simó Schwartz Jr., Maria Luisa Tutino, Antonio Villaverde (Corresponding Author)

    Research output: Contribution to journalReview Articlepeer-review

    107 Citations (Scopus)


    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.
    Original languageEnglish
    Pages (from-to)140-153
    JournalBiotechnology Advances
    Issue number2
    Publication statusPublished - 2013
    MoE publication typeA2 Review article in a scientific journal


    • Aggregation
    • biotherapeutics
    • microbial cells
    • protein folding
    • protein production
    • recombinant protein


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