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Nitroalkanes as Versatile Nucleophiles for Enzymatic Synthesis of Noncanonical Amino Acids

Romney, David K. and Sarai, Nicholas S. and Arnold, Frances H. (2019) Nitroalkanes as Versatile Nucleophiles for Enzymatic Synthesis of Noncanonical Amino Acids. ACS Catalysis, 9 (9). pp. 8726-8730. ISSN 2155-5435. PMCID PMC7709965. doi:10.1021/acscatal.9b02089. https://resolver.caltech.edu/CaltechAUTHORS:20190903-130240854

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Abstract

C–C bond-forming reactions often require nucleophilic carbon species rarely compatible with aqueous reaction media, thus restricting their appearance in biocatalysis. Here we report the use of nitroalkanes as a structurally versatile class of nucleophilic substrates for C–C bond formation catalyzed by variants of the β-subunit of tryptophan synthase (TrpB). The enzymes accept a wide range of nitroalkanes to form noncanonical amino acids, where the nitro group can serve as a handle for further modification. Using nitroalkane nucleophiles greatly expands the scope of compounds made by TrpB variants and establishes nitroalkanes as a valuable substrate class for biocatalytic C–C bond formation.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1021/acscatal.9b02089DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709965/PubMed CentralArticle
ORCID:
AuthorORCID
Romney, David K.0000-0003-0498-7597
Sarai, Nicholas S.0000-0002-4655-0038
Arnold, Frances H.0000-0002-4027-364X
Additional Information:© 2019 American Chemical Society. Received: May 20, 2019; Revised: August 14, 2019; Published: August 20, 2019. This work was funded by the Rothenberg Innovation Initiative at Caltech and by a NIH R01 grant (GM125887-01A1). The authors thank Kai Chen for assistance with experiments and Ella Watkins-Dulaney and Kelly Zhang for helpful discussions regarding the manuscript. The authors declare the following competing financial interest(s): The contents of this paper are the subject of a patent application submitted by Caltech, and some authors are entitled to a royalty on revenues arising from that patent.
Funders:
Funding AgencyGrant Number
Rothenberg Innovation Initiative (RI2)UNSPECIFIED
NIHGM125887-01A1
Subject Keywords:biocatalysis C−C bond formation tryptophan synthase noncanonical amino acid nitroalkane
Issue or Number:9
PubMed Central ID:PMC7709965
DOI:10.1021/acscatal.9b02089
Record Number:CaltechAUTHORS:20190903-130240854
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190903-130240854
Official Citation:Nitroalkanes as Versatile Nucleophiles for Enzymatic Synthesis of Noncanonical Amino Acids. David K. Romney, Nicholas S. Sarai, and Frances H. Arnold. ACS Catalysis 2019 9 (9), 8726-8730. DOI: 10.1021/acscatal.9b02089
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:98395
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:03 Sep 2019 22:58
Last Modified:10 Feb 2022 00:39

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