期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 54, 期 11, 页码 3351-3367出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201409470
关键词
biocatalysis; enzymes; non-natural activity; promiscuity; protein engineering
资金
- Department of the Navy, Office of Naval Research [N00014-11-10205]
- Jacobs Institute for Molecular Engineering for Medicine at Caltech
- Gordon and Betty Moore Foundation [GBMF2809]
- National Science Foundation, Office of Chemical, Bioengineering, Environmental and Transport Systems SusChEM Initiative [CBET-1403077]
- Ruth L. Kirschstein Fellowship from the National Institutes of Health [F32EB015846]
- Div Of Chem, Bioeng, Env, & Transp Sys
- Directorate For Engineering [1403077] Funding Source: National Science Foundation
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.
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