Microbial factories for recombinant pharmaceuticals

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.

Production of functional inclusion bodies in endotoxin-free Escherichia coli

“…coli is the most common cell factory for the production of recombinant proteins (Ferrer-Miralles and Villaverde 2013), including biopharmaceuticals for use in humans (Ferrer-Miralles et al 2009). Like in other Gram-negative bacteria, the outer membrane of E. coli contains LPS as a main constituent that is released upon cell disruption to obtain intracellular products of biotechnological interest.…”

Heterologous laccase production and its role in industrial applications

“…The versatility and scaling-up possibilities of the recombinant protein production opened up new commercial opportunities for their industrial uses. 23 Enzyme productivity can be increased by the use of multiple gene copies, strong promoters and efficient signal sequences, properly designed to address proteins to the extracellular medium, thus simplifying downstream processing. Moreover, protein production from pathogenic or toxin-producing species can take advantage of safer or even GRAS (generally recognized as safe) microbial hosts.…”

Respuesta de IFN-ɤ e IL-4 en ratones inoculados con una proteína G recombinante del virus de la rabia

“…La producción de proteínas recombinantes en líneas celulares de mamíferos, insectos y plantas y animales transgénicas se están incorporando progresivamente en las actividades de producción (18) . El objetivo de este estudio fue analizar la respuesta de IFN- e IL4 en ratones inoculados con la proteína G del virus de la rabia (GpRV) expresada en baculovirus y maíz.…”

“…Recombinant protein production in mammalian and insect cell lines and transgenic plants and animals are being progressively incorporated into production activities (18) . The aim of this study was to analyse the response of IFN- and IL4 in inoculated mice with rabies virus G protein (GpRV) expressed in baculovirus and maize.…”