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The quest for molecular quasi‐species in ligand‐activity space and its application to directed enzyme evolution
Author(s) -
Mannervik Bengt,
Runarsdottir Arna
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.04.024
Subject(s) - molecular evolution , ligand (biochemistry) , directed evolution , biology , identification (biology) , evolutionary biology , enzyme , computational biology , genetics , biochemistry , ecology , phylogenetics , gene , receptor , mutant
We propose that the proper evolving unit in enzyme evolution is not a single “fittest molecule”, but a cluster of related variants denoted a “quasi‐species”. A distribution of variants provides genetic variability and thereby reduces the risk of inbreeding and evolutionary dead‐ends. Different matrices of substrates or activity modulators will lead to different selection criteria and divergent evolutionary trajectories. We provide examples from our directed evolution of glutathione transferases illustrating the interplay between libraries of enzyme variants and ligand matrices in the identification of quasi‐species. The ligand matrix is shown to be crucial to the outcome of the search for novel activities. In this sense the experimental system resembles the biological environment in governing the evolution of enzymes.