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      Putting the Spotlight Back on Plant Suspension Cultures

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          Abstract

          Plant cell suspension cultures have several advantages that make them suitable for the production of recombinant proteins. They can be cultivated under aseptic conditions using classical fermentation technology, they are easy to scale-up for manufacturing, and the regulatory requirements are similar to those established for well-characterized production systems based on microbial and mammalian cells. It is therefore no surprise that taliglucerase alfa (Elelyso®)—the first licensed recombinant pharmaceutical protein derived from plants—is produced in plant cell suspension cultures. But despite this breakthrough, plant cells are still largely neglected compared to transgenic plants and the more recent plant-based transient expression systems. Here, we revisit plant cell suspension cultures and highlight recent developments in the field that show how the rise of plant cells parallels that of Chinese hamster ovary cells, currently the most widespread and successful manufacturing platform for biologics. These developments include medium optimization, process engineering, statistical experimental designs, scale-up/scale-down models, and process analytical technologies. Significant yield increases for diverse target proteins will encourage a gold rush to adopt plant cells as a platform technology, and the first indications of this breakthrough are already on the horizon.

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          A Revised Medium for Rapid Growth and Bio Assays with Tobacco Tissue Cultures

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            Recombinant protein folding and misfolding in Escherichia coli.

            The past 20 years have seen enormous progress in the understanding of the mechanisms used by the enteric bacterium Escherichia coli to promote protein folding, support protein translocation and handle protein misfolding. Insights from these studies have been exploited to tackle the problems of inclusion body formation, proteolytic degradation and disulfide bond generation that have long impeded the production of complex heterologous proteins in a properly folded and biologically active form. The application of this information to industrial processes, together with emerging strategies for creating designer folding modulators and performing glycosylation all but guarantee that E. coli will remain an important host for the production of both commodity and high value added proteins.
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              Biopharmaceutical benchmarks 2014.

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                Author and article information

                Contributors
                Journal
                Front Plant Sci
                Front Plant Sci
                Front. Plant Sci.
                Frontiers in Plant Science
                Frontiers Media S.A.
                1664-462X
                11 March 2016
                2016
                : 7
                : 297
                Affiliations
                [1] 1Plant Cell Biology Laboratory, Universidade Nova de Lisboa, Instituto de Tecnologia Química e Biológica António Xavier Oeiras, Portugal
                [2] 2Fraunhofer-Institut für Molekularbiologie und Angewandte Oekologie (IME), Integrated Production Platforms Aachen, Germany
                [3] 3Biology VII, Institute for Molecular Biotechnology, RWTH Aachen University Aachen, Germany
                Author notes

                Edited by: Domenico De Martinis, ENEA Italian National Agency for New Technologies, Energy and Sustainable Economic Development, Italy

                Reviewed by: Heiko Rischer, VTT Technical Research Centre of Finland Ltd., Finland; Karen Ann McDonald, University of California, Davis, USA

                *Correspondence: Tanja Holland tanja.holland@ 123456ime.fraunhofer.de

                This article was submitted to Plant Biotechnology, a section of the journal Frontiers in Plant Science

                Article
                10.3389/fpls.2016.00297
                4786539
                27014320
                5eb8cf72-c7e5-4c1c-8ceb-b7c4cf43b7f2
                Copyright © 2016 Santos, Abranches, Fischer, Sack and Holland.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 December 2015
                : 25 February 2016
                Page count
                Figures: 1, Tables: 2, Equations: 0, References: 137, Pages: 12, Words: 11304
                Funding
                Funded by: Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa 10.13039/501100005856
                Award ID: IB/0001/2012
                Award ID: PTDC/BIA-PLA/2411/2012
                Award ID: UID/Multi/04551/2013
                Funded by: Fundação para a Ciência e a Tecnologia 10.13039/501100001871
                Funded by: Fraunhofer-Gesellschaft 10.13039/501100003185
                Categories
                Plant Science
                Review

                Plant science & Botany
                plant suspension cultures,biopharmaceuticals,by-2,protein production,plant cell cultures

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