title: Unconventional microbial systems for the cost-efficient production of high-quality protein therapeutics.
abstract: 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.
authors.affiliation: CIBER en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Corchero
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gasser
authors.forename: David
authors.initials: D
authors.lastname: Resina
authors.forename: Wesley
authors.initials: W
authors.lastname: Smith
authors.forename: Ermenegilda
authors.initials: E
authors.lastname: Parrilli
authors.forename: Felícitas
authors.initials: F
authors.lastname: Vázquez
authors.forename: Ibane
authors.initials: I
authors.lastname: Abasolo
authors.forename: Maria
authors.initials: M
authors.lastname: Giuliani
authors.forename: Jussi
authors.initials: J
authors.lastname: Jäntti
authors.forename: Pau
authors.initials: P
authors.lastname: Ferrer
authors.forename: Markku
authors.initials: M
authors.lastname: Saloheimo
authors.forename: Diethard
authors.initials: D
authors.lastname: Mattanovich
authors.forename: Simó
authors.initials: S
authors.lastname: Schwartz
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Tutino
authors.forename: Antonio
authors.initials: A
authors.lastname: Villaverde
mesh_terms: D000818:Animals; D016825:Chlamydomonas reinhardtii / Q000235:genetics / Q000378:metabolism; D003362:Cost-Benefit Analysis; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D007218:Industrial Microbiology / Q000191:economics / Q000379:methods*; D008322:Mammals; D010843:Pichia / Q000235:genetics / Q000378:metabolism; D015202:Protein Engineering / Q000191:economics / Q000379:methods*; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D031161:Pseudoalteromonas / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000627:therapeutic use*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D014242:Trichoderma / Q000235:genetics / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins