That in the lab happens in hours, what nature needs millennia, is worth the Nobel Prize! This results in tailor-made enzymes for medicines and biofuels.
Evolution is a magic bag. It has produced primal bacteria that feel at home in a hundred degrees of warm water, jellyfish that light their way through the ocean - and, of course, extremely complex creatures like humans. Hundreds of thousands of chemical reactions occur every millisecond in our bodies. And only because certain proteins, enzymes, catalyze them. It is these protein molecules that, if you like, are at the bottom of all life, and yet they are just as they are by chance, through evolution. The problem is that they often take thousands of years to improve in what they do.
Not fast enough for what this year's Nobel laureates had in mind with such enzymes. They saw that nothing changes the biological building blocks so precisely and makes them as powerful as evolution itself. At the same time, they had no desire to wait until nature alone produced variants that would be optimally used in medicine or industry. The biochemist Frances Arnold on the one hand and the biologist George Smith and the molecular biologist Sir Gregory Winter on the other are honored with the highest honors in science because they deliberately exploited the power of evolutionary chance. They laid the foundation for a greener chemistry, biofuels and brand new powerful drugs: highly effective antibodies. They let the evolution in test tubes in time lapse run. What takes millennia in nature happens in hours in the lab.
The basis for medicines with antibodies
Enzymes are highly complex protein molecules that initiate chemical reactions - with a multitude of tasks: they break down toxins so that the cells of the human body do not suffer, they stick sugar molecules together to create energy stores, or produce toxic substances to decompose pathogens , Enzymes consist of chains of mostly several hundred amino acids. Their blueprints are recorded in genes. When produced by bacteria or human cells, they wrap and twist many times before they really take effect. Over millions of years, the genes and thus the function of such enzymes changed. No matter if in humans, porcupines or the malaria parasites, it was always best to survive those whose enzymes worked particularly well or at least were not harmful. Evolution, if you like, is always busy producing better enzymes.
This was also stated by the American Frances Arnold. She did her award-winning research at the renowned California Institute for Technology (Caltech), where she still works today. When she started this work in the 1980s, she was already aware of the power of enzymes in chemistry. With much headache they tried to penetrate the structure of the enzymes and to change them specifically to make them more effective. Something that Arnold later called "a rather arrogant approach." She took a different path and used the power of evolutionary chance to find better enzymes. Something later called "directed evolution".
The power of chance tamed
Arnold's research began with the enzyme subtilisin, which cuts other protein chains like scissors and is contained in detergents, for example (FASEB Journal: Arnold, 1993). She tried to change the enzyme so that it unfolds its full potential in a certain solvent, in which it functioned only moderately until then. To achieve this, the biochemist isolated the gene of subtilisin and made sure that its genetic material mutated randomly - as usual in the course of evolution. Then she examined the resulting new proteins to see how well they worked and selected the best ones. Apart from chance, selection is the second driver of evolution. The researcher repeated this step-by-step process four times, creating a library of mutant enzymes. At the end there was a protein complex that was 256 times as active as the starting enzyme (see picture). Arnold had rebuilt the evolution.
The principle of directed evolution works as follows: (1) Random mutations are induced in the gene for the enzyme to be altered. (2) The genes are inserted into bacteria that use them as a template and randomly produce mutant enzymes. (3) It is necessary to test the modified enzymes. Researchers select those that most efficiently drive the desired chemical reaction. What is not good, is disposed of. (4) Then add new random mutations into the genes of the chosen enzymes. The cycle starts again. © ohan Jarnestad / The Royal Swedish Academy of Sciences
The procedure she proposed is the one that is still valid today. Arnold's life's work is to have perfected her with other researchers. One of them is William Stemmer, who died in 2013 and probably was not honored today. Nobel prizes are not awarded posthumously, according to the statutes. Stemmer introduced DNA shuffling. In this method, the DNA, so the genetic material, similar enzymes, but from different organisms used for directed evolution.
Enzymes that have evolved through directed evolution are already used in many areas of industry and medicine: biofuel production, environmentally friendly chemical development, industrial waste detoxification, or drug manufacturing. And that's exactly where the other two this year's Nobel Laureates come into play: the American George P. Smith and the British Sir Gregory P. Winter.
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