High-value products from plants: The challenges of process optimization

Current Opinion in Biotechnology

Volumn 32, Issue , 2015, Pages 156-162

  Fischer, Rainer ^a,b   Vasilev, Nikolay ^a   Twyman, Richard M ^c   Schillberg, Stefan ^a  

^a FRAUNHOFER INSTITUTE FOR MOLECULAR BIOLOGY AND APPLIED ECOLOGY IME   (Germany)

^b RWTH AACHEN UNIVERSITY   (Germany)

^c TRM Ltd   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

OPTIMIZATION; RECOMBINANT PROTEINS;

COMMERCIAL PRODUCTIONS; INTEGRATED PRODUCTION; PHARMACEUTICAL PRODUCTS; PROOF-OF-PRINCIPLE EXPERIMENTS; SMALL MOLECULES; TARGET MOLECULE;

MOLECULES;

BENZYLISOQUINOLINE DERIVATIVE; INDOLE ALKALOID; SESQUITERPENOID; TAXOID; TROPANE ALKALOID; VEGETABLE PROTEIN; RECOMBINANT PROTEIN;

BIOMASS PRODUCTION; CELL SUSPENSION; CROP PRODUCTION; CULTURE MEDIUM; DOWNSTREAM PROCESSING; GENETIC ENGINEERING; METABOLIC ENGINEERING; MOLECULAR FARMING; NONHUMAN; PHYTOCHEMISTRY; PLANT CELL; PLANT GENE; PLANT PRODUCT; PROCESS OPTIMIZATION; REVIEW; ADAPTATION; GENETICS; METABOLISM; PLANT; TRANSGENIC PLANT;

ADAPTATION, PHYSIOLOGICAL; PLANTS; PLANTS, GENETICALLY MODIFIED; RECOMBINANT PROTEINS;

EID: 84920283009     PISSN: 09581669     EISSN: 18790429     Source Type: Journal    
DOI: 10.1016/j.copbio.2014.12.018     Document Type: Review

References (55)

1. Farré G., Blancquaert D., Capell T., Van Der Straeten D., Christou P., Zhu C. Engineering complex metabolic pathways in plants. Ann Rev Plant Biol 2014, 65:187-223.
2. Stoger E., Fischer R., Moloney M., Ma J.K. Plant molecular pharming for the treatment of chronic and infectious diseases. Annu Rev Plant Biol 2014, 65:743-768.
3. Fischer R., Schillberg S., Hellwig S., Twyman R.M., Drossard J. GMP issues for recombinant plant-derived pharmaceutical proteins. Biotechnol Adv 2012, 30:434-439.
4. Fischer R., Schillberg S., Buyel J.F., Twyman R.M. Commercial aspects of pharmaceutical protein production in plants. Curr Pharm Des 2013, 19:5471-5477.
5. Paul M.J., Teh A.Y., Twyman R.M., Ma J.K. Target product selection-where can molecular pharming make the difference?. Curr Pharm Des 2013, 19:5478-5485.
6. Gottschalk U. Bioseparation in antibody manufacturing: the good, the bad and the ugly. Biotechnol Prog 2008, 24:496-503.
7. Rischer H., Häkkinen S.T., Ritala A., Seppänen-Laakso T., Miralpeix B., Capell T., Christou P., Oksman-Caldentey K.M. Plant cells as pharmaceutical factories. Curr Pharm Des 2013, 19:5640-5660.
8. Chandra S., Chandra R. Engineering secondary metabolite production in hairy roots. Phytochemistry Rev 2011, 10:371-395.
9. Bai C., Rivera S.M., Medina V., Alves R., Vilaprinyo E., Sorribas A., Canela R., Capell T., Sandmann G., Christou P., Zhu C. An in vitro system for the rapid functional characterization of genes involved in carotenoid biosynthesis and accumulation. Plant J 2014, 77:464-475.
10. Zhu C., Naqvi S., Breitenbach J., Sandmann G., Christou P., Capell T. Combinatorial genetic transformation generates a library of metabolic phenotypes for the carotenoid pathway in maize. Proc Natl Acad Sci USA 2008, 105:18232-18237.
11. Loos A., Steinkellner H. Plant glyco-biotechnology on the way to synthetic biology. Front Plant Sci 2014, 5:523.
12. Mandal M.K., Fischer R., Schillberg S., Schiermeyer A. Inhibition of protease activity by antisense RNA improves recombinant protein production in Nicotiana tabacum cv Bright Yellow 2 (BY-2) suspension cells. Biotechnol J 2014, 9:1065-1073.
13. Várallyay É., Oláh E., Havelda Z. Independent parallel functions of p19 plant viral suppressor of RNA silencing required for effective suppressor activity. Nucleic Acids Res 2014, 42:599-608.
14. Hood E.E., Devaiah S.P., Fake G., Egelkrout E., Teoh K.T., Requesens D.V., Hayden C., Hood K.R., Pappu K.M., Carroll J., Howard J.A. Manipulating corn germplasm to increase recombinant protein accumulation. Plant Biotechnol J 2012, 10:20-30.
15. Kirchhoff J., Raven N., Boes A., Roberts J.L., Russell S., Treffenfeldt W., Fischer R., Schinkel H., Schiermeyer A., Schillberg S. Monoclonal tobacco cell lines with enhanced recombinant protein yields can be generated from heterogeneous cell suspension cultures by flow sorting. Plant Biotechnol J 2012, 10:936-944.
16. Raven N., Rasche S., Kuehn C., Anderlei T., Klöckner W., Schuster F., Henquet M., Bosch D., Büchs J., Fischer R., Schillberg S. Scaled-up manufacturing of recombinant antibodies produced by plant cells in a 200-L orbitally-shaken disposable bioreactor. Biotechnol Bioeng 2015, 112:308-321.
17. Vasilev N., Schmitz C., Dong L., Ritala A., Imseng N., Häkkinen S.T., van der Krol S., Eibl R., Oksman-Caldentey K.M., Bouwmeester H., Fischer R., Schillberg S. Comparison of plant-based expression platforms for the heterologous production of geraniol. Plant Cell Tiss Organ Cult 2014, 117:373-380.
18. Buyel J.F., Fischer R. Predictive models for transient protein expression in tobacco (Nicotiana tabacum L.) can optimize process time, yield, and downstream costs. Biotechnol Bioeng 2012, 109:2575-2588.
19. Dodd A.N., Salanthia N., Hall A., Kévei E., Tóth R., Nagy F., Hibberd J.M., Millar A.J., Webb A.A. Plant circadian clocks increase photosynthesis, growth, survival and competitive advantage. Science 2005, 309:630-633.
20. Stevens L.H., Stoopen G.M., Elbers I.J.W., Molthoff J.W., Bakker H.A., Lommen A., Bosch D., Jordi W. Effect of climate conditions and plant developmental stage on the stability of antibodies expressed in transgenic tobacco. Plant Physiol 2000, 124:173-182.
21. Schillberg S., Raven N., Fischer R., Twyman R.M., Schiermeyer A. Molecular farming of pharmaceutical proteins using plant suspension cell and tissue cultures. Curr Pharm Des 2013, 19:5531-5542.
22. Holland T., Blessing D., Hellwig S., Sack M. The in-line measurement of plant cell biomass using radio frequency impedance spectroscopy as a component of process analytical technology. Biotechnol J 2013, 8:1231-1240.
23. Murashige T., Skoog F. A revised medium for rapid growth and bioassay with tobacco tissue cultures. Physiol Planta 1962, 15:473-497.
24. + ratio influences plant regeneration and auxin sensitivity in primary callus derived from immature embryos of indica rice (Oryza sativa L.). J Plant Physiol 1990, 136:362-367.
25. Niedz R.P. Growth of embryogenic sweet orange callus on media varying in the ratio of nitrate to ammonium nitrogen. Plant Cell Tiss Organ Cult 1994, 39:1-5.
26. Holland T., Sack M., Rademacher T., Schmale K., Altmann F., Stadlmann J., Fischer R., Hellwig S. Optimal nitrogen supply as a key to increased and sustained production of a monoclonal full-size antibody in BY-2 suspension culture. Biotechnol Bioeng 2010, 107:278-289.
27. Ullisch D.A., Müller C.A., Maibaum S., Kirchhoff J., Schiermeyer A., Schillberg S., Roberts J.L., Treffenfeldt W., Büchs J. Comprehensive characterization of Nicotiana tabacum BY-2 cell growth leads to doubled GFP concentration by media optimization. J Biosci Bioeng 2012, 113:242-248.
28. Buyel J.F., Fischer R. Characterization of complex systems using the design of experiments approach: transient protein expression in tobacco as a case study. J Vis Exp 2014, 83:e51216.
29. Vasilev N., Schmitz C., Grömping U., Fischer R., Schillberg S. Assessment of cultivation factors that affect biomass and geraniol production in transgenic tobacco cell suspension cultures. PLoS One 2014, 9:e104620.
30. Vasilev N., Grömping U., Lipperts A., Raven N., Fischer R., Schillberg S. Optimization of BY-2 cell suspension culture medium for the production of a human antibody using a combination of fractional factorial designs and the response surface method. Plant Biotechnol J 2013, 11:867-874.
31. Häkkinen S.T., Raven N., Henquet M., Laukkanen M.L., Anderlei T., Pitkänen J.P., Twyman R.M., Bosch D., Oksman-Caldentey K.M., Schillberg S., Ritala A. Molecular farming in tobacco hairy roots by triggering the secretion of a pharmaceutical antibody. Biotechnol Bioeng 2014, 111:336-346.
32. Wilson S.A., Roberts S.C. Recent advances towards development and commercialization of plant cell culture processes for the synthesis of biomolecules. Plant Biotechnol J 2012, 10:249-268.
33. Twyman R.M., Schillberg S., Fischer R. Optimizing the yield of recombinant pharmaceutical proteins in plants. Curr Pharm Des 2013, 19:5486-5494.
34. Menkhaus T.J., Bai Y., Zhang C., Nikolov Z.L., Glatz C.E. Considerations for the recovery of recombinant proteins from plants. Biotechnol Prog 2004, 20:1001-1014.
35. Arakawa T., Tsumoto K., Ejima D. Alternative downstream processes for production of antibodies and antibody fragments. Biochim Biophys Acta 2014, 1844:2032-2040.
36. Buyel J.F., Gruchow H.M., Boes A., Fischer R. Rational design of a host cell protein heat precipitation step can simplify the subsequent purification of recombinant proteins from tobacco. Biochem Eng J 2014, 88:162-170.
37. Buyel J.F., Fischer R. Downstream processing of biopharmaceutical proteins produced in plants: the pros and cons of flocculants. Bioengineered 2014, 5:138-142.
38. Buyel J.F., Fischer R. Flocculation increases the efficacy of depth filtration during the downstream processing of recombinant pharmaceutical proteins produced in tobacco. Plant Biotechnol J 2014, 12:240-252.
39. Buyel JF, Opdensteinen P, Fischer R: Cellulose-based filter aids increase the capacity of depth filters during the downstream processing of plant-derived biopharmaceutical proteins. Biotechnol J (in press).
40. Buyel J.F., Fischer R. Generic chromatography-based purification strategies accelerate the development of downstream processes for biopharmaceutical proteins produced in plants. Biotechnol J 2014, 9:566-577.
41. Buyel J.F., Woo J.A., Cramer S.M., Fischer R. The use of quantitative structure-activity relationship models to develop optimized processes for the removal of tobacco host cell proteins during biopharmaceutical production. J Chromatogr A 2013, 1322:18-28.
42. Buyel J.F., Fischer R. Scale-down models to optimize a filter train for the downstream purification of recombinant pharmaceutical proteins produced in tobacco leaves. Biotechnol J 2014, 9:415-425.
43. Buyel JF, Fischer R: A juice extractor can simplify the downstream processing of plant-derived biopharmaceutical proteins compared to blade-based homogenizers. Process Biochem (in review).
44. FDA/USDA Draft Guidance. Drugs, Biologics and Medical Devices Derived from Bioengineered Plants for Use in Humans and Animals 2002, FDA, Rockville MD.
45. EMEA Committee for Proprietary Medicinal Products (CPMP) Points to Consider on Quality Aspects of Medicinal Products Containing Active Substances Produced by Stable Transgene Expression in Higher Plants 2002, EMA, London UK, (EMEA/CPMP/BWP/764/02).
46. Spok A., Twyman R.M., Fischer R., Ma J.K.C., Sparrow P.A.C. Evolution of a regulatory framework for plant-made pharmaceuticals. Trends Biotechnol 2008, 26:506-517.
47. Aviezer D., Almon-Brill E., Shaaltiel Y., Hashmueli S., Bartfeld D., Mizrachi S., Liberman Y., Freeman A., Zimran A., Galun E. Novel enzyme replacement therapy for Gaucher disease: ongoing Phase III clinical trial with recombinant human glucocerebrosidase expressed in plant cells. Mol Genet Metab 2009, 96:S13-S14.
48. Aviezer D., Brill-Almon E., Shaaltiel Y., Hashmueli S., Bartfeld D., Mizrachi S., Liberman Y., Freeman A., Zimran A., Galun E. A plant-derived recombinant human glucocerebrosidase enzyme-a preclinical and phase I investigation. PLoS One 2009, 4:e4792.
49. EMEA Committee for Proprietary Medicinal Products (CPMP) Guideline on the Quality of Biological Active Substances Produced by Stable Transgene Expression in Higher Plants 2008, EMA, London, UK, (EMEA/CHMP/BWP/48316/2006).
50. Wirz H., Sauer-Budge A.F., Briggs J., Sharpe A., Sudong S., Sharon A. Automated production of plant-based vaccines and pharmaceuticals. J Lab Automat 2012, 17:449-457.
51. Huang T., McDonald K.A. Bioreactor systems for in vitro production of foreign proteins using plant cell cultures. Biotechnol Adv 2012, 30:398-409.
52. Raven N., Schillberg S., Kirchhoff J., Brändli J., Imseng N., Eibl R. Growth of BY-2 suspension cells and plantibody production in single-use bioreactors. Single-use Technology in Biopharmaceutical Manufacture 2011, 251-261. John Wiley & Sons, Hoboken, NJ. R. Eibl, D. Eibl (Eds.).
53. Farré G., Twyman R.M., Zhu C., Capell T., Christou P. Knowledge-driven approaches for engineering complex metabolic pathways in plants. Curr Opin Biotechnol 2015, 32:54-60.
54. Bortesi L., Fischer R. The CRISPR/Cas9 system for plant genome editing and beyond. Biotechnol Adv. 2015, 10.1016/j.biotechadv.2014.12.006.
55. Miralpeix B., Rischer H., Häkkinen S.T., Ritala A., Seppänen-Laakso T., Oksman-Caldentey K.M., Capell T., Christou P. Metabolic engineering of plant secondary products: which way forward?. Curr Pharm Des 2013, 19:5622-5639.