- The 2018 Nobel Prize for Chemistry was conferred upon Frances Arnold, George Smith and Gregory Winter for harnessing the power of evolution to make proteins more useful for medicine and chemistry.
- While Frances Arnold won half of the prize for her work on ‘directed evolution of enzymes’, the other half was shared between George Smith and Sir Gregory Winter, “for the phage display of antibodies”.
- The directed evolution of enzymes and the phage display of antibodies are significant in greener chemicals industry, produce new materials, manufacture sustainable biofuels, mitigate disease and save lives.
- Besides, Francis Arnold became the fifth woman to win a chemistry Nobel.
- Directed Evolution of Enzymes
- Frances Arnold won half the prize for fundamentally changing chemistry by designing new enzymes using the process of directed evolution.
What are enzymes?
- Enzymes are complex protein molecules that catalyse chemical reactions occurring in living organisms.
- Enzymes are basically made up of 20 different kinds of amino acids.
- Further a single enzyme can consist of several thousand amino acids linked through long chains.
Evolution and enzymes
- Ever since life on earth appeared about 3.7 billion years ago, all organisms have adapted to the environment through bio-chemical reactions occurring within them.
- Living organisms extract materials and energy from the environmental and use them for their survival.
- The process of using this energy and other biological processes depend on the bio-chemical reactions that occur within the organisms.
- These chemical reactions are catalysed by various enzymes that speed up or slow down the chemical reactions depending on the requirement for organism’s survival.
- Further this chemistry of life is basically programmed into our genes, inherited and developed through the process of evolution.
- Evolution is a process through which small changes in genes change the chemistry gradually developing into new and complex forms of life.
- Thus by developing new enzymes we can catalyse chemistry that does not exist in nature, producing entirely new bio-chemical materials.
Directed evolution and development of new enzymes
- Earlier approaches to develop new enzymes were to remodel the enzymes.
- However given the complexity of enzymes, developing new properties was found to be difficult.
- Instead of remodeling the enzyme, Francis Arnold tweaked the natural process of evolution to produce new enzymes.
Principle of directed evolution
- Arnold tried to change an enzyme called subtilisin which breaks down milk protein, casein, through what is called directed evolution.
- The new enzyme she tried to create was to catalyse chemical reactions in an organic solvent called dimethylformamide instead of in water-based solution.
- Arnold introduced mutations in the subtilisin’s genetic code and introduced these mutated enzymes into bacteria that produced thousands of different variants of subtilisin.
- This process of producing new variant of the enzyme by introducing small changes and allowing to naturally go through the process of evolution is called directed evolution.
- She then selected the variant of subtilisin that was most effective in breaking down the milk protein, casein in a solution with 35 per cent DMF.
- She subsequently introduced a new round of random mutations in this subtilisin, which yielded a variant that worked even better in DMF.
- In the third generation of subtilisin she found a variant that worked 256 times better in DMF than the original enzyme.
- The new enzymes developed through directed evolution have become important tools in the manufacture of various substances, such as pharmaceuticals.
- New enzymes are synthesized to speed up chemical reactions, produce fewer by-products and in some cases, to exclude the heavy metals, thus reducing the environmental impact.
- Scientists have also used this process to develop enzymes that transform simple sugars to isobutanol, an energy-rich substance that can be used for the production of biofuels and greener plastics.
- Phage display of antibodies
- As mentioned above one half of the Nobel Prize in Chemistry was shared by George Smith and Sir Gregory Winter.
- George Smith developed a method known as phage display to evolve new proteins.
- Phage display is a method where a bacteriophage – a virus that infects bacteria – is used to evolve new proteins.
- Using phage display, Gregory Winter developed antibodies through directed evolution of antibodies, with the aim of producing new pharmaceuticals.
- Using the method of phage display, a pharmaceutical entirely based on a human antibody adalimumab was developed.
- This antibody basically neutralises a protein that drives inflammation in many autoimmune diseases.
- Further using this method various antibodies are developed to be used in the treatment of rheumatoid arthritis, psoriasis, inflammatory bowel diseases, cancer antibodies, antrax, autoimmune disease known as lupus etc.
- Besides, antibodies are being developed using this method to combat Alzheimer’s disease.