Moss Bioreactor
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A moss bioreactor with '' Physcomitrella patens'' A moss bioreactor is a photobioreactor used for the cultivation and propagation of
moss Mosses are small, non-vascular plant, non-vascular flowerless plants in the taxonomic phylum, division Bryophyta (, ) ''sensu stricto''. Bryophyta (''sensu lato'', Wilhelm Philippe Schimper, Schimp. 1879) may also refer to the parent group bryo ...
es. It is usually used in molecular farming for the production of recombinant protein using
transgenic A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change the ...
moss. In environmental science moss bioreactors are used to multiply peat mosses e.g. by the Mossclone consortium to monitor
air pollution Air pollution is the presence of substances in the Atmosphere of Earth, air that are harmful to humans, other living beings or the environment. Pollutants can be Gas, gases like Ground-level ozone, ozone or nitrogen oxides or small particles li ...
. Moss is a very frugal
photoautotrophic Photoautotrophs are organisms that can utilize light energy from sunlight, and elements (such as carbon) from inorganic compounds, to produce organic materials needed to sustain their own metabolism (i.e. autotrophy). Such biological activities ...
organism that has been kept ''
in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...
'' for research purposes since the beginning of the 20th century. The first moss bioreactors for the
model organism A model organism is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workings of other organisms. Mo ...
''
Physcomitrella patens ''Physcomitrella patens'' is a synonym of ''Physcomitrium patens'', the spreading earthmoss. It is a moss, a bryophyte used as a model organism for studies on plant evolution, development, and physiology. Distribution and ecology ''Physcomitr ...
'' were developed in the 1990s to comply with the safety standards regarding the handling of genetically modified organisms and to gain sufficient
biomass Biomass is a term used in several contexts: in the context of ecology it means living organisms, and in the context of bioenergy it means matter from recently living (but now dead) organisms. In the latter context, there are variations in how ...
for experimental purposes.


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
nutrient A nutrient is a substance used by an organism to survive, grow and reproduce. The requirement for dietary nutrient intake applies to animals, plants, fungi and protists. Nutrients can be incorporated into cells for metabolic purposes or excret ...
s and
mineral In geology and mineralogy, a mineral or mineral species is, broadly speaking, a solid substance with a fairly well-defined chemical composition and a specific crystal structure that occurs naturally in pure form.John P. Rafferty, ed. (2011): Mi ...
s needed for growth of the moss. To ensure a maximum growth rate, the moss is kept at the protonema stage by continuous mechanical disruption, e.g. by using rotating blades. Once the density of the culture has reached a certain threshold, the lack of nutrients and the increasing concentration of
phytohormone Plant hormones (or phytohormones) are signal molecules, produced within plants, that occur in extremely low concentrations. Plant hormones control all aspects of plant growth and development, including embryogenesis, the regulation of organ si ...
s in the medium triggers the differentiation of the protonema to the adult
gametophyte A gametophyte () is one of the two alternating multicellular phases in the life cycles of plants and algae. It is a haploid multicellular organism that develops from a haploid spore that has one set of chromosomes. The gametophyte is the se ...
. 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.


Production of biopharmaceuticals

Various
biopharmaceutical A biopharmaceutical, also known as a biological medical product, or biologic, is any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. Different from totally synthesized pharmaceuticals, t ...
s have already been produced using moss bioreactors. Ideally, the recombinant protein can be directly purified from the culture medium. One example for this production method is
factor H Factor H (FH) is a member of the regulators of complement activation family and is a complement control protein. It is a large (155 kilodaltons), soluble glycoprotein that circulates in human plasma (at typical concentrations of 200–300 m ...
: this
molecule A molecule is a group of two or more atoms that are held together by Force, attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemi ...
is part of the human
complement system The complement system, also known as complement cascade, is a part of the humoral, innate immune system and enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inf ...
. Defects in the corresponding
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
are associated with human diseases such as severe
kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...
and retinal disorders. Biologically active recombinant factor H was produced in a moss bioreactor for the first time in 2011. The enzyme alpha-galactosidase now is allowed to be produced in moss bioreactors by the German
Federal Institute for Drugs and Medical Devices The Federal Institute for Drugs and Medical Devices (in German: Bundesinstitut für Arzneimittel und Medizinprodukte – ''BfArM'') is the medical regulatory body in Germany. It operates under the Federal Ministry of Health (BMG). It is headqua ...
. It will be tested as enzyme replacement therapy in the treatment of Fabry's disease. The
clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...
phase 1 was completed in 2017.Greenovation gelingt der Durchbruc
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See also

* Algae bioreactor *
Bioreactor A bioreactor is any manufactured device or system that supports a biologically active environment. In one case, a bioreactor is a vessel in which a chemical reaction, chemical process is carried out which involves organisms or biochemistry, biochem ...
* Molecular farming * Photobioreactor *'' Sphagnum palustre'' *''
Physcomitrella patens ''Physcomitrella patens'' is a synonym of ''Physcomitrium patens'', the spreading earthmoss. It is a moss, a bryophyte used as a model organism for studies on plant evolution, development, and physiology. Distribution and ecology ''Physcomitr ...
''


References

Biotechnology Bioreactors