Plant bioreactors refer to the use of transgenic plants and cell cultures of plants to make unlimited quantities of commercially important substances like recombinant proteins including antibodies and vaccines using biotechnology oriented techniques.
Most of the research has been directed towards using plant bioreactors to make the following
• Therapeutic proteins
• Edible vaccines
• Antibodies for immunotherapy
Using genetic engineering, cereal plants, fruits plants, legumes and vegetable plants have the capacity to become low cost bioreactors to make molecules that in the normal scheme of things would not have been available from plants. Human growth hormone was the first drug that was produced using plant bioreactors, in this case from the transgenic tobacco.
We will now discuss the different plant bioreactor expression systems especially with reference to where the protein compartmentalizes in these bioreactors.
Seed-based plant bioreactors
Plant seeds accumulate large amount of proteins during their development stage and therefore plant bioreactors based on seed platforms are reckoned as suitable for storing recombinant proteins.
An example is the successful expression of the human lysosomal enzyme alpha-L-iduronidase in Arabidopsis thaliana seeds. In seed bioreactors the expression of recombinant proteins is controlled using seed specific promoters like for example in maize globulin-1, and in rice glutelin promoter Gt-1. The advantage of these systems is that, proteins do not degrade at ambient temperature and are stable for long term storage.
However factors such as specificity of expression and subcellular storage environment would decide how specifically seeds could be used for producing desired molecules.
Seed Protein Storage Vacuole Bioreactors
In seed bioreactors, protein storage vacuoles comprising the sub compartments namely, matrix, globoid and crystalloid are dominant compartments for storing recombinant proteins. The matrix is suitable for soluble storage proteins, globoid for hydrolytic enzyme, and crystalloid for BP-80 TMD and the CT of alpha-tonoplast intrinsic protein sequences.
Seed Oil Body Bioreactors
Seed oil body is encircled by the protein oleosin which are ideal carriers for heterologous protein production and also provide a recognition signal for lipase binding during oil mobilization in seedlings. Seed oil body is bioreactors that can store large amount of macromolecules.
An example is the expression of fusion protein containing oleosin and the β-glucuronidase in seed oil body. Another example is the manufacture of the anticoagulant hirudin in the oil body of seeds Brassica napus and Brassica carinata
Plant Suspension Cultures
They are used to express recombinant proteins, secondary metabolites and antibodies transported to subcellular organelles. For example, is the expression of 80-kDa human lysosomal protein (controlled by 3 5S CaMV and a signal peptide) in transgenic tobacco BY-2 cells culture media.
Hairy Root System Bioreactor
The Hairy Root System with its rhizosecretion is due to infection of the soil bacterium-Agrobaterium rhizogenes. It offers extreme biosynthetic stability and is suitable for making biopharmaceuticals as for example scopolamine in Hyoscyamus muticus L. hairy root culture
Insulin, interferons and other biopharmaceutical proteins can be made using Chloroplast bioreactor. One method is foreign genes are inserted into nuclear chromosomes and with peptides target expressed proteins into chloroplast. An example is the high yield in the expression of human serum albumin protein in chloroplast.
Comparitive study of plant bioreactor systems
Cost wise, seed, hairy root, cultured cell suspension, oil body and chloroplast bioreactor systems are on the cheaper side to set-up and in terms of product stability seed and oil body systems offer the best prospects. In terms of scale-up capacity seed, oil body and chloroplast bioreactor systems are most suitable.
Advantages and Disadvantages
Generally the practice has been to use cloned animal cells to make antibodies for use as drugs. But there is always the remote chance of unwanted allergic reactions due to antibodies of animal origin, and that apart, contamination of the antibody product due to proteins and viruses of animal origin is a distinct possibility. Such problems do not arise when plants are used to make antibodies because plants do not generally serve as hosts for human and animal pathogens
Making recombinant proteins in transgenic plants is relatively cheap as compared to the cost of running fermentors although extraction and purification processes have to be efficient. For example these proteins are expressed in the plant seeds which all look similar and the recombinant protein has to be cleaved enzymatically or by other means.
But these seeds can be stored and processed when required unlike animal cell production methods which require immediate purification.
More and more uses of plant bioreactors are coming up these days. For example, plant bioreactors are being investigated for making enzymes suitable for use in feed additives and in food. Another use of plants is to make genetically engineered plants that can produce seeds which can function as a delivery mechanism for various industrial enzymes
As you can see these processes go far beyond the application of biotechnology in traditional agriculture, and so today, transgenic plants can produce on a mass scale proteins for agricultural, veterinary and pharmaceutical use. These processes are mainly carried out by cost conscious biopharma and enzyme companies.
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