Moss bioreactor

Moss bioreactor with Physcomitrella patens

A moss bioreactor is a photobioreactor used for the cultivation and propagation of mosses. It is usually used in molecular farming for the production of recombinant protein using transgenic moss.

Mosses are very frugal photoautotrophic organisms that have been kept in vitro for research purposes since the beginning of the 20th century.^[1]

The first moss bioreactors for the model organism Physcomitrella patens were developed in the 1990s to comply with the safety standards regarding the handling of genetically modified organisms and to gain sufficient biomass for experimental purposes.^[2]

Functional Principle

The moss bioreactor is used to cultivate moss in a suspension culture in agitated, and aerated liquid medium. The culture is kept under lighting with temperature and pH value held constant. The culture medium – often a minimal medium – contains all nutrients and minerals needed for growth of the moss.^[3]

To ensure a maximum growth rate, the moss is kept at the protonema stage by continuous mechanical disruption, e.g. by using rotating blades. .^[4] Once the density of the culture has reached a certain threshold, the lack of nutrients and the increasing concentration of phytohormones in the medium triggers the differentiation of the protonema to the adult gametophyte. At this point the culture has to be diluted with fresh medium if it is intended for further use.

According to the intended yield, this basic principle can be adapted to various types and sizes of bioreactors. The cultivation chamber can, for example, consist of a column, a tube, or exchangeable plastic bags.^[5]

Production of Biopharmaceuticals

Various biopharmaceuticals have already been produced using moss bioreactors.^[6] Ideally, the recombinant protein can be directly purified from the culture medium .^[7] One example for this production method is factor H: this molecule is part of the human complement system. Defects in the corresponding gene are associated with human diseases such as severe kidney and retinal disorders. Biologically active recombinant factor H was produced in a moss bioreactor for the first time in 2011.^[8]

References

1. ^ Hohe, A., R. Reski (2005): From axenic spore germination to molecular farming: one century of bryophyte in vitro culture. Plant Cell Rep. 23, 513-521. doi:10.1007/s00299-004-0894-8
2. ^ Reutter K, Reski R (1996) Production of a heterologous protein in bioreactor cultures of fully differentiated moss plants. Plant Tissue Cult Biotechnol 2:142–147 [1]
3. ^ Hohe, A., R. Reski (2005): Control of growth and differentiation of bioreactor cultures of Physcomitrella by environmental parameters. Plant Cell, Tissue and Organ Culture 81, 307-311. doi:10.1007/s11240-004-6656-z
4. ^ Decker, E.L., R. Reski (2004): The moss bioreactor. Curr. Opinion Plant Biol. 7, 166-170 doi:10.1016/j.pbi.2004.01.002
5. ^ Homepage of greenovation GmbH, showing various types of moss bioreactors: [2]
6. ^ Eva L. Decker, Ralf Reski (2008): Current achievements in the production of complex biopharmaceuticals with moss bioreactors. Bioprocess and Biosystems Engineering 31(1), 3-9 PMID 17701058
7. ^ Baur, A., R. Reski, G. Gorr (2005): 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. Plant Biotech. J. 3, 331-340 doi:10.1111/j.1467-7652.2005.00127.x
8. ^ Büttner-Mainik, A., J. Parsons, H. Jérome, A. Hartmann, S. Lamer, A. Schaaf, A. Schlosser, P.F. Zipfel, R. Reski, E.L. Decker (2011): Production of biologically active recombinant human factor H in Physcomitrella. Plant Biotechnology Journal 9, 373-383. doi:10.1111/j.1467-7652.2010.00552.x

See also

• Bioreactor
• Photobioreactor
• Molecular farming
• Physcomitrella patens