Microorganisms and factories, how are they related?
It is well known that proteins of human origin have a high pharmaceutical value; they are very appreciated and cannot be obtained as other natural resources. Diabetics, for example, traditionally acquired their to doses of insulin (hormone responsible for the regulation of blood glucose) from pig or cow pancreas extractions. Currently we have microbe-based technologies that help us manufacture proteins of interest at a low cost.
So, proteins from microbes are compatible with humans?
Not exactly. The development of recombinant DNA technologies in the late 70’s and its approval by the FDA in the early 80’s allowed us today to have a wide range of pharmaceutical products adapted to our needs and without a moral dilemma regarding animal use or experimentation.
Let’s go by parts; what are recombinant DNA technologies?
As we already introduced in the article skiing among bacteria, we can slightly modify some microbes to produce proteins of interest. The expression of new proteins is called heterologous expression. In a simplified way, the process goes as follows:
- A microorganism (bacteria or yeast) of interest is selected. It should not cause infections, intoxications or other affectations to humans and/or animals. Microorganisms with a good history and without cases of pathogenesis are usually assigned the GRAS label (Generally Recognized As Safe). Comprehensive studies of the microorganism itself and its cellular machinery are necessary in order to continue.
- A sequence encoding the protein of interest is selected and, if necessary, adapted to the codon use of the chosen microorganism. To simplify, it is like translating the manufacturing instructions into the microbe’s language so that the final product is like the original.
- We introduce our gene through a vector and the microorganism expresses the protein as if it were its own. The only step left will be purification.
The use of mammalian, plant or insect cells can facilitate safety and compatibility studies to produce protein. The only weak point is that these cultures grow slowly and are not as profitable compared to mass production using bacteria or yeast. Currently, most therapeutic proteins are produced in bacteria or mammalian cell lines.
In addition to insulin, which is produced in Escherichia coli, heterologous expression is used to synthesize vaccine components. For example, antigens (remember our article on vaccines?) used in vaccines for hepatitis B, hantavirus or papilloma virus are produced with the yeast Saccharomyces cerevisiae, the same used to make bread and beer!
It does not end here… heterologous expression has much to offer!
The possibility of producing customized proteins in expression systems has opened the door to an infinity of studies in environmental, industrial or clinical research lines! For example…
- Imagine that we can add a piece of DNA to make a protein fluorescent. This allows the study of its exact location inside the cell or in a tissue, as well as to determine if under certain conditions our protein is produced or not. It can be used to study the behavior of proteins related to cancer or other diseases.
- We can also produce high amounts of enzymes such as cellulases, responsible for breaking down cellulose into smaller molecules. Cellulases are crucial components in industrial processes such as cotton processing, paper-making, juice extraction or the preparation of food additives for animals.
And these are just two examples, can you think of any interesting application? Let us know!
- Human insulin receives FDA approval. FDA Drug Bull. 1982 Dec; 12(3):18-9.
- Reena A, Munivenkatappa S, Muniveerappa B, Vinayagamurthy B. (2016). An Overview of Heterologous Expression Host Systems for the Production of Recombinant Proteins. Advances in Animal and Veterinary Sciences. 4. 346-356. 10.14737/journal.aavs/2016/4.7.346.356.
- Priti N Desai, Neeta Shrivastava, Harish Padh. (2010). Production of heterologous proteins in plants: Strategies for optimal expression. Biotechnology Advances. 28(4):427-435. https://doi.org/10.1016/j.biotechadv.2010.01.005
- Bhat MK. Cellulases and related enzymes in biotechnology. Biotechnol Adv. 2000;18:355–383. Link. doi: 10.1016/S0734-9750(00)00041-0