CaltechAUTHORS
  A Caltech Library Service

Tryptophan Synthase: Biocatalyst Extraordinaire

Watkins-Dulaney, Ella and Straathof, Sabine and Arnold, Frances (2020) Tryptophan Synthase: Biocatalyst Extraordinaire. ChemBioChem . ISSN 1439-4227. (In Press) https://resolver.caltech.edu/CaltechAUTHORS:20200717-104339058

[img] PDF - Accepted Version
See Usage Policy.

5Mb

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20200717-104339058

Abstract

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 (Ser) to make l ‐tryptophan (Trp); native TrpS complexes possess fairly broad specificity for indole analogs, 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
Related URLs:
URLURL TypeDescription
https://doi.org/10.1002/cbic.202000379DOIArticle
ORCID:
AuthorORCID
Watkins-Dulaney, Ella0000-0002-0585-1598
Arnold, Frances0000-0002-4027-364X
Additional Information:© 2020 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim. Accepted manuscript online: 16 July 2020; Manuscript accepted: 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: FHA is a co-founder of Aralez Bio (San Leandro, CA), which uses TrpB variants to produce ncAAs.
Funders:
Funding AgencyGrant Number
Rothenberg Innovation Initiative (RI2)UNSPECIFIED
NIHR01GM125887
Subject Keywords:biocatalysis; amino acids; Enzyme; Biotransformation; Protein engineering
Record Number:CaltechAUTHORS:20200717-104339058
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200717-104339058
Official Citation:Watkins-Dulaney, E..J., Straathof, S. and Arnold, F..H. (2020), Tryptophan Synthase: Biocatalyst Extraordinaire. ChemBioChem. Accepted Author Manuscript. doi:10.1002/cbic.202000379
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:104427
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:17 Jul 2020 18:01
Last Modified:17 Jul 2020 18:01

Repository Staff Only: item control page