Grogan, Gideon James orcid.org/0000-0003-1383-7056, McKean, Iain, Sadler, Joanna et al. (5 more authors) (2019) S-Adenosyl Methionine Cofactor Modifications Enhance the Biocatalytic Repertoire of Small Molecule C-Alkylation. Angewandte Chemie International Edition. pp. 1-7. ISSN 1433-7851
Abstract
A tandem enzymatic strategy to enhance the scope of Calkylation of small molecules via the in situ formation of S-adenosyl methionine (SAM) cofactor analogues is described. A solventexposed channel present in the SAM-forming enzyme SalL tolerates 5'-chloro-5’-deoxyadenosine (ClDA) analogues modified at the 2position of the adenine nucleobase. Coupling SalL-catalyzed cofactor production with C-(m)ethyl transfer to coumarin substrates catalyzed by the methyltransferase (MTase) NovO forms C(m)ethylated coumarins in superior yield and greater substrate scope relative to that obtained using cofactors lacking nucleobase modifications. Establishing the molecular determinants which influence C-alkylation provides the basis to develop a late-stage enzymatic platform for the preparation of high value small molecules
Metadata
Item Type: | Article |
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Authors/Creators: |
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Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) |
Depositing User: | Pure (York) |
Date Deposited: | 04 Nov 2019 15:10 |
Last Modified: | 08 Feb 2025 00:35 |
Published Version: | https://doi.org/10.1002/anie.201908681 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1002/anie.201908681 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:153066 |