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La evolución dirigida y la coevolución tecnologías de frontera para mejorar las funciones en las proteínas

Journal: Alianzas y Tendencias BUAP (Vol.7, No. 25)

Publication Date:

Authors : ; ; ; ; ;

Page : 52-65

Keywords : coevolution; directed evolution; phage display; proteins;

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Abstract

In the last 10 years, scientists have been able to simulate natural evolution in laboratories through the process of directed evolution, which begins with a target gene or sequence for which a mutant gene library is generated using random mutagenesis. After producing such libraries through the technique of error-prone PCR (epPCR), they are subjected to selection or screening for the identification of improved proteins towards a particular function or functions when compared to the protein that originated them. Another methodology to harness the products of the long evolutionary history is the coevolution analysis, which is very helpful when no selection strategy is feasible and the screening method available to sift mutants is very slow, limiting the number of mutants that can be sampled to find an improved variant. In the coevolution analysis, the variation patterns of residues in contact are analyzed, because mutations in these residues change the residue packing in the protein, thus, producing modifications in function, stability, selectivity, even when residue substitution is far from the active site. The selection acting on proteins force two residues in contact to vary in a correlated way when they are important for function. Therefore, directed evolution coupled with coevolution are some of the most successful techniques in molecular and frontier biology that allow us to explore and improve the functions of a large number of proteins of medical, biotechnological, industrial interest, etc., in a very short time.

Last modified: 2022-03-31 15:24:01