A moss bioreactor with '' Physcomitrella patens'' A moss bioreactor is a photobioreactor used for the cultivation and

propagation Propagation can refer to: * Chain propagation in a chemical reaction mechanism *Crack propagation, the growth of a crack during the fracture of materials * Propaganda, non-objective information used to further an agenda * Reproduction, and other fo ...

moss Mosses are small, non-vascular flowerless plants in the taxonomic division Bryophyta (, ) '' sensu stricto''. Bryophyta (''sensu lato'', Schimp. 1879) may also refer to the parent group bryophytes, which comprise liverworts, mosses, and hor ...

es. It is usually used in molecular farming for the production of

recombinant protein Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be fou ...

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 Environmental science is an interdisciplinary academic field that integrates physics, biology, and geography (including ecology, chemistry, plant science, zoology, mineralogy, oceanography, limnology, soil science, geology and physical geograp ...

moss bioreactors are used to multiply

peat moss ''Sphagnum'' is a genus of approximately 380 accepted species of mosses, commonly known as sphagnum moss, peat moss, also bog moss and quacker moss (although that term is also sometimes used for peat). Accumulations of ''Sphagnum'' can store wa ...

es e.g. by the

Mossclone The Framework Programmes for Research and Technological Development, also called Framework Programmes or abbreviated FP1 to FP9, are funding programmes created by the European Union/European Commission to support and foster research in the Europea ...

consortium to monitor

air pollution Air pollution is the contamination of air due to the presence of substances in the atmosphere that are harmful to the health of humans and other living beings, or cause damage to the climate or to materials. There are many different types ...

. Moss is a very frugal

photoautotrophic Photoautotrophs are organisms that use light energy and inorganic carbon to produce organic materials. Eukaryotic photoautotrophs absorb energy through the chlorophyll molecules in their chloroplasts while prokaryotic photoautotrophs use chlorophyll ...

organism that has been kept ''

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...

'' for research purposes since the beginning of the 20th century. The first moss

bioreactors A bioreactor refers to 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, ...

for the

model organism A model organism (often shortened to model) 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 workin ...

Physcomitrella patens ''Physcomitrium patens'', (synonym: ''Physcomitrella patens'' ) the spreading earthmoss, is a moss (bryophyte) used as a model organism for studies on plant evolution, development, and physiology. Distribution and ecology ''Physcomitrella pat ...

'' 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 plant-based material used as a fuel for heat or electricity production. It can be in the form of wood, wood residues, energy crops, agricultural residues, and waste from industry, farms, and households. Some people use the terms bi ...

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 A growth medium or culture medium is a solid, liquid, or semi-solid designed to support the growth of a population of microorganisms or cells via the process of cell proliferation or small plants like the moss ''Physcomitrella patens''. Different ...

—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 chemical compound with a fairly well-defined chemical composition and a specific crystal structure that occurs naturally in pure form.John P. Rafferty, ed. ( ...

s needed for growth of the moss. To ensure a maximum growth rate, the moss is kept at the

protonema A protonema (plural: protonemata) is a thread-like chain of cells that forms the earliest stage of development of the gametophyte (the haploid phase) in the life cycle of mosses. When a moss first grows from a spore, it starts as a ''germ tube'', ...

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 hormone (or phytohormones) are signal molecules, produced within plants, that occur in extremely low concentrations. Plant hormones control all aspects of plant growth and development, from embryogenesis, the regulation of organ size, pat ...

s in the medium triggers the differentiation of the protonema to the adult

gametophyte A gametophyte () is one of the two alternation of generations, alternating multicellular organism, multicellular phases in the life cycles of plants and algae. It is a haploid multicellular organism that develops from a haploid spore that has on ...

. 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. Sphagnum palustre in Bioreactor

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 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 micrograms ...

: this

molecule A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...

is part of the human

complement system The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and at ...

. Defects in the corresponding

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

are associated with human diseases such as severe

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

and retinal disorders. Biologically active recombinant factor H was produced in a moss bioreactor for the first time in 2011. The enzyme

alpha-galactosidase α-Galactosidase ( EC 3.2.1.22, α-GAL, α-GAL A; systematic name α-D-galactoside galactohydrolase) is a glycoside hydrolase enzyme that catalyses the following reaction: : Hydrolysis of terminal, non-reducing α-D-galactose residues in α-D- ...

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 headquarte ...

. It will be tested as enzyme replacement therapy in the treatment of

Fabry's disease Fabry disease, also known as Anderson–Fabry disease, is a rare genetic disease that can affect many parts of the body, including the kidneys, heart, and skin. Fabry disease is one of a group of conditions known as lysosomal storage diseases. T ...

. The

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

phase 1 was completed in 2017.Greenovation gelingt der Durchbruc
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References

Biotechnology Bioreactors

Functional principle

Production of biopharmaceuticals

See also

References