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Tryptophan Synthase: Biocatalyst Extraordinaire

Watkins-Dulaney, Ella and Straathof, Sabine and Arnold, Frances (2021) Tryptophan Synthase: Biocatalyst Extraordinaire. ChemBioChem, 22 (1). pp. 5-16. ISSN 1439-4227. PMCID PMC7935429. doi:10.1002/cbic.202000379.

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Tryptophan synthase (TrpS) has emerged as a paragon of noncanonical amino acid (ncAA) synthesis and is an ideal biocatalyst for synthetic and biological applications. TrpS catalyzes an irreversible, C−C bond‐forming reaction between indole and serine to make l‐tryptophan; native TrpS complexes possess fairly broad specificity for indole analogues, but are difficult to engineer to extend substrate scope or to confer other useful properties due to allosteric constraints and their heterodimeric structure. Directed evolution freed the catalytically relevant TrpS β‐subunit (TrpB) from allosteric regulation by its TrpA partner and has enabled dramatic expansion of the enzyme's substrate scope. This review examines the long and storied career of TrpS from the perspective of its application in ncAA synthesis and biocatalytic cascades.

Item Type:Article
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URLURL TypeDescription CentralArticle
Watkins-Dulaney, Ella0000-0002-0585-1598
Arnold, Frances0000-0002-4027-364X
Additional Information:© 2020 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim. Issue Online: 07 January 2021; Version of Record online: 22 September 2020; Accepted manuscript online: 16 July 2020; Manuscript revised: 15 July 2020; Manuscript received: 12 June 2020. The authors thank Sabine Brinkmann‐Chen, Nicholas Porter, Patrick Almhjell, David Miller, David Romney, and Christina Boville for helpful discussions and comments on the manuscript. This work was supported by the Rothenberg Innovation Initiative (RI2) program 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. Conflict of interest: F.H.A. is a co‐founder of Aralez Bio (San Leandro, CA), which uses TrpB variants to produce ncAAs.
Funding AgencyGrant Number
Rothenberg Innovation Initiative (RI2)UNSPECIFIED
Subject Keywords:biocatalysis; amino acids; Enzyme; Biotransformation; Protein engineering
Issue or Number:1
PubMed Central ID:PMC7935429
Record Number:CaltechAUTHORS:20200717-104339058
Persistent URL:
Official Citation:Tryptophan Synthase: Biocatalyst Extraordinaire. E. Watkins-Dulaney, S. Straathof, F. Arnold, ChemBioChem 2021, 22, 5; DOI: 10.1002/cbic.202000379
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:104427
Deposited By: Tony Diaz
Deposited On:17 Jul 2020 18:01
Last Modified:10 Feb 2022 17:45

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