Directed Enzyme Evolution: A novel technique to speed up evolution and create specialized proteins

What would you think if I told you that it is possible to speed up millions of years of evolution in a test tube on the lab?

Well, this is exactly what three scientists independently achieved. The 2018 chemistry Nobel Prizes developed a crazy and revolutionary process called direct evolution. This process uses evolutionary concepts to produce novel proteins with the desired characteristics to be used in distinct fields such as the pharmaceutical industry, the production of renewable energy among others. The revolutionary idea of directed evolution was developed by Prof. Frances H. Arnold, Prof. George P. Smith, and the emeritus research leader Gregory P. Winter. 

Nobel Prize in Chemistry,2018 Nobel Prizes,Chemistry Nobel prize

                                                    Source: Hindustan Times.                                                            Frances H. Arnold, a professor of chemical engineering, was awarded half the Nobel prize for being the first person to use evolutionary techniques since 1996 to accelerate the production and modification of enzymes. Meanwhile, Prof. George P. Smith and Gregory P. Winter worked on using direct enzyme evolution to improve the synthesis of more efficient enzymes used in the pharmaceutical field.

But what is exactly is Directed Evolution?

                             “Life Evolution”                                Credit: GIPHY

Nature over the years has used evolution to create the diverse environment around us. Over the generations, nature has made sure that only the desired and competent genes pass the filter of natural selection. The individuals with the “strongest” characteristics thrive in the environment, leaving better fit  populations. Similarly, these principles were used by the pioneer scientists to accelerate evolutionary processes and replicate pathways in which enzymes are naturally selected.

“Humans have exploited the concept of Darwinian evolution for thousands of years with selective breeding,” said Stefan Lutz, the chairman of the chemistry department at Emory University. “Directed evolution takes this same principle and applies it to the lab.”

Directed evolution works by inducing repeated mutations on bacteria or viruses, creating mutated populations that give rise to the desired enzymes. In each turn of bred the chosen enzyme is artificially selected allowing it to be more specialized over time. Different methods are used to induce random mutations; methods such as  chemical mutagenesis, UV radiation, and DNA recombination. The novel part is the use of the called error-prone PCR, which induces random mutagenesis in the bacterial strains. This technique is well suited for this job because it allows the scientists to keep track of the number of genetic doubling events occurring. This unique process optimizes the use of mutations for evolving enzymes to an improved version of themselves with a more stable folding, solubility, and binding affinity. With this technique, the scientists have rendered enzymes 256 times more effective than before.

Graphic illustrating the work flow for the directed evolution of enzymes

                                     “Directed Enzyme Evolution Technique”                                       Source: Quanta Magazine

The magic of this technique is that directed evolution can be used  as an alternative pathway to solve questions related to life evolution, as well as to study different research areas related to industrial and pharmaceutical processes. The improvement of proteins is used in industrial processes to manufacture biocatalysts that are resistant to extreme temperatures and very harsh environments. Evolved enzymes can be also used as a sustainable way to accelerate chemical reactions for the production of drugs in a very cost-efficient way, and to maximize the production of  certain drugs. Surprisingly, scientists also hope this new technique will help generate new sources of renewable energy, by using the catalytic power of enzymes.

                              ” 3D Enzyme Structure”                                   Source: GIPHY

The discoveries from three inspiring scientists models paved the way for future scientists to use this technique to solve urgent global problems  such as the development of renewable energy sources.

Daniela Yanez

 

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