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Engineering enzymes for noncanonical amino acid synthesis

Almhjell, Patrick J. and Boville, Christina E. and Arnold, Frances H. (2018) Engineering enzymes for noncanonical amino acid synthesis. Chemical Society Reviews, 47 (24). pp. 8980-8997. ISSN 0306-0012. http://resolver.caltech.edu/CaltechAUTHORS:20181008-141850453

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Abstract

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1039/c8cs00665bDOIArticle
ORCID:
AuthorORCID
Almhjell, Patrick J.0000-0003-0977-841X
Boville, Christina E.0000-0002-2577-9343
Arnold, Frances H.0000-0002-4027-364X
Additional Information:© 2018 The Royal Society of Chemistry. The article was received on 12 Aug 2018 and first published on 03 Oct 2018. The authors would like to thank Dr Sabine Brinkmann-Chen, Dr David Romney, Prof. Andrew Buller, and Bradley Boville for helpful discussion and comments on the manuscript. C. E. B. was supported by a postdoctoral fellowship from the Resnick Sustainability Institute. This work was funded by the Jacobs Institute for Molecular Engineering for Medicine (Caltech) and the Rothenberg Innovation Initiative (formerly CI2), and by the National Institute Of General Medical Sciences of the National Institutes of Health under Award Number R01GM125887. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. There are no conflicts to declare.
Group:Resnick Sustainability Institute
Funders:
Funding AgencyGrant Number
Resnick Sustainability InstituteUNSPECIFIED
Jacobs Institute for Molecular Engineering for MedicineUNSPECIFIED
Rothenberg Innovation Initiative (RI2)UNSPECIFIED
NIHR01GM125887
Record Number:CaltechAUTHORS:20181008-141850453
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20181008-141850453
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:90158
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:08 Oct 2018 21:39
Last Modified:10 Dec 2018 18:52

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