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Issue 24, 2018
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Engineering enzymes for noncanonical amino acid synthesis

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The standard proteinogenic amino acids grant access to a myriad of chemistries that harmonize to create life. Outside of these twenty canonical protein building blocks are countless noncanonical amino acids (ncAAs), either found in nature or created by man. Interest in ncAAs has grown as research has unveiled their importance as precursors to natural products and pharmaceuticals, biological probes, and more. Despite their broad applications, synthesis of ncAAs remains a challenge, as poor stereoselectivity and low functional-group compatibility stymie effective preparative routes. The use of enzymes has emerged as a versatile approach to prepare ncAAs, and nature's enzymes can be engineered to synthesize ncAAs more efficiently and expand the amino acid alphabet. In this tutorial review, we briefly outline different enzyme engineering strategies and then discuss examples where engineering has generated new ‘ncAA synthases’ for efficient, environmentally benign production of a wide and growing collection of valuable ncAAs.

Graphical abstract: Engineering enzymes for noncanonical amino acid synthesis

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Publication details

The article was received on 12 Aug 2018 and first published on 03 Oct 2018

Article type: Tutorial Review
DOI: 10.1039/C8CS00665B
Chem. Soc. Rev., 2018,47, 8980-8997

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    Engineering enzymes for noncanonical amino acid synthesis

    P. J. Almhjell, C. E. Boville and F. H. Arnold, Chem. Soc. Rev., 2018, 47, 8980
    DOI: 10.1039/C8CS00665B

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