Moss bioreactor

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Moss bioreactor with Physcomitrella patens

A moss bioreactor is a special form of the photobioreactor , propagation and serves cultivation of moss . As a rule, transgenic moss is cultivated in a moss bioreactor for the production of recombinant protein . This biotechnological process is also known as molecular pharming . In environmental science , bioreactors are used, for example, to multiply peat moss , as in the Mossclone research group , to monitor air pollution, particularly due to heavy metals .

Since mosses are relatively frugal, photoautotrophic organisms, various types of mosses were already cultivated in vitro at the beginning of the 20th century . In order to meet the safety guidelines for handling genetically modified organisms and to be able to obtain sufficient biomass for experimental investigations, Ralf Reski developed the first bioreactors for the model organism Physcomitrella patens in the 1990s .

functionality

A moss bioreactor is based on the principle of a suspension culture: The moss is cultivated in a fluid, agitated nutrient medium under lighting and ventilation at a constant temperature. The culture medium - often a minimal medium - contains the nutrients and trace elements required for growth ; the pH value is kept constant by adding acid or alkali to the medium.

In order to achieve the greatest possible increase in biomass , the moss is kept in the protonema stage. This is done by continuously, mechanically shredding the growing Protonema threads, for example using rotating blades. When the density of the biomass reaches a critical point, as a result of the decreasing supply of nutrients and the increasing content of plant signal substances ( phytohormones ) in the medium, the protonema increasingly differentiates from the actual "moss plant". If the culture is to be continued, part of the culture is heavily diluted with fresh nutrient medium and reapplied.

Depending on the desired yield, this functional principle can be implemented using different shapes and sizes of bioreactors. In addition to column reactors of various volumes, there are also tubular reactors and reactors with exchangeable plastic culture bags for protein production on an industrial scale.

The swamp peat moss Sphagnum palustre is cultivated in this moss bioreactor

Manufacture of biopharmaceuticals

Various biopharmaceuticals have already been produced in moss bioreactors with Physcomitrella patens . Here, the recombinant protein can ideally be purified from the culture medium. Factor H is an example: This molecule is part of the human complement system , a defect in the corresponding gene leads to various kidney and eye diseases. Biologically active, recombinant factor H was first produced in moss bioreactors at the beginning of 2011. The enzyme α-galactosidase A may carry the following approval Federal Institute for Drugs and Medical Devices are manufactured in moss bioreactors, for a clinical study that analyzes whether the disease Fabry disease can be alleviated more efficiently with this enzyme replacement therapy. The clinical phase 1 study was completed in 2017.

See also

Individual evidence

  1. Walter Schmidt, Michael Brendler: Second career nose. In: Badische Zeitung. April 14, 2012.
  2. Video Mosses are supposed to control air pollution. In: Euronews . June 3, 2013, accessed June 10, 2013.
  3. A. Hohe, R. Reski: From axenic spore germination to molecular farming: one century of bryophyte in vitro culture. In: Plant Cell Rep. 23, 2005, pp. 513-521. doi: 10.1007 / s00299-004-0894-8
  4. K. Reutter, R. Reski: Production of a heterologous protein in bioreactor cultures of fully differentiated moss plants. In: Plant Tissue Cult Biotechnol. 2, 1996, pp. 142-147. (PDF) ( Memento of the original from October 4, 2011 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. @1@ 2Template: Webachiv / IABot / www.plant-biotech.net
  5. ^ A. Hohe, R. Reski: Control of growth and differentiation of bioreactor cultures of Physcomitrella by environmental parameters. In: Plant Cell, Tissue and Organ Culture. 81, 2005, pp. 307-311. doi: 10.1007 / s11240-004-6656-z
  6. ^ EL Decker, R. Reski: The moss bioreactor. Curr. In: Opinion Plant Biol. 7, 2004, pp. 166-170 doi: 10.1016 / j.pbi.2004.01.002
  7. ^ Eva L. Decker, Ralf Reski : Current achievements in the production of complex biopharmaceuticals with moss bioreactors. In: Bioprocess and Biosystems Engineering. 31 (1), 2008, pp. 3-9. PMID 17701058 .
  8. A. Baur, R. Reski, G. Gorr: Enhanced recovery of a secreted recombinant human growth factor using stabilizing additives and by co-expression of human serum albumin in the moss Physcomitrella patens. In: Plant Biotech. J. 3, 2005, pp. 331-340. doi: 10.1111 / j.1467-7652.2005.00127.x
  9. Jump up A. Büttner-Mainik, J. Parsons, H. Jérome, A. Hartmann, S. Lamer, A. Schaaf, A. Schlosser, PF Zipfel, R. Reski, EL Decker: Production of biologically active recombinant human factor H in Physcomitrella. In: Plant Biotechnology Journal. 9, 2011, pp. 373-383. doi: 10.1111 / j.1467-7652.2010.00552.x
  10. Homepage of Greenovation: Approval to begin a Phase I clinical trial in Europe for moss-aGal (agalsidase) produced in Mossbioreactors. Retrieved October 18, 2015 .
  11. Ralf Reski, Juliana Parsons, Eva L. Decker: Moss-made pharmaceuticals: from bench to bedside. In: Plant Biotechnology Journal. 2015. doi: 10.1111 / pbi.12401
  12. Greenovation achieves the breakthrough portal goingpublic ( memento of the original from January 11, 2018 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. @1@ 2Template: Webachiv / IABot / www.goingpublic.de

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