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Higher-order epistasis shapes the fitness landscape of a xenobiotic-degrading enzyme

Yang, Gloria; Anderson, Dave W.; Baier, Florian; Dohmen , Elias; Hong, Nansook; Carr, Paul D; Kamerlin, Shina CL; Jackson, Colin; Bornberg-Bauer, Erich; Tokuriki, Nobuhiko


Characterizing the adaptive landscapes that encompass the emergence of novel enzyme functions can provide molecular insights into both enzymatic and evolutionary mechanisms. Here, we combine ancestral protein reconstruction with biochemical, structural and mutational analyses to characterize the functional evolution of methyl-parathion hydrolase (MPH), an organophosphate-degrading enzyme. We identify five mutations that are necessary and sufficient for the evolution of MPH from an ancestral...[Show more]

CollectionsANU Research Publications
Date published: 2019
Type: Journal article
Source: Nature Chemical Biology
DOI: 10.1038/s41589-019-0386-3


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