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Expanding the Enzyme Universe: Accessing Non‐Natural Reactions by Mechanism‐Guided Directed Evolution
Author(s) -
Renata Hans,
Wang Z. Jane,
Arnold Frances H.
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201409470
Subject(s) - extant taxon , directed evolution , natural (archaeology) , mechanism (biology) , protein engineering , chemistry , enzyme , biochemical engineering , combinatorial chemistry , computational biology , biology , evolutionary biology , biochemistry , epistemology , philosophy , gene , engineering , paleontology , mutant
High selectivity and exquisite control over the outcome of reactions entice chemists to use biocatalysts in organic synthesis. However, many useful reactions are not accessible because they are not in nature’s known repertoire. In this Review, we outline an evolutionary approach to engineering enzymes to catalyze reactions not found in nature. We begin with examples of how nature has discovered new catalytic functions and how such evolutionary progression has been recapitulated in the laboratory starting from extant enzymes. We then examine non‐native enzyme activities that have been exploited for chemical synthesis, with an emphasis on reactions that do not have natural counterparts. Non‐natural activities can be improved by directed evolution, thus mimicking the process used by nature to create new catalysts. Finally, we describe the discovery of non‐native catalytic functions that may provide future opportunities for the expansion of the enzyme universe.