Structural and functional basis of C-methylation of coumarin scaffolds by NovO

Sadler, Joanna C. and Chung, Chun-wa H. and Mosley, Julie E. and Burley, Glenn A. and Humphreys, Luke D. (2017) Structural and functional basis of C-methylation of coumarin scaffolds by NovO. ACS Chemical Biology, 12 (2). pp. 374-379. ISSN 1554-8937 (https://doi.org/10.1021/acschembio.6b01053)

[thumbnail of Sadler-etal-ACSCB-2017-C-methylation-of-coumarin-scaffolds-by-NovO]
Preview
 Text. Filename: Sadler_etal_ACSCB_2017_C_methylation_of_coumarin_scaffolds_by_NovO.pdf
Accepted Author Manuscript
Download (4MB)| Preview

Abstract

C-methylation of aromatic small molecules by C-methyltransferases (C-MTs) is an important biological transformation that involves C–C bond formation using S-adenosyl-l-methionine (SAM) as the methyl donor. Here, two advances in the mechanistic understanding of C-methylation of the 8-position of coumarin substrates catalyzed by the C-MT NovO from Streptomyces spheroides are described. First, a crystal structure of NovO reveals the Arg116-Asn117 and His120-Arg121 motifs are essential for coumarin substrate binding. Second, the active-site His120 is responsible for deprotonation of the phenolic 7-hydroxyl group on the coumarin substrate, activating the rate-determining methyl transfer step from SAM. This work expands our mechanistic knowledge of C-MTs, which could be used in the downstream development of engineered biocatalysts for small molecule C-alkylations.

ORCID iDs

Sadler, Joanna C. ORCID logoORCID: https://orcid.org/0000-0002-8442-0760, Chung, Chun-wa H., Mosley, Julie E., Burley, Glenn A. and Humphreys, Luke D.;
  • Item type:Article
    ID code:60153
    Dates:
    Date
    Event
    17 February 2017
    Published
    9 January 2017
    Published Online
    9 January 2017
    Accepted
    Notes:This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Chemical Biology, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acschembio.6b01053.
    Subjects:Science > Chemistry
    Department:Faculty of Science > Pure and Applied Chemistry
    Technology and Innovation Centre > Bionanotechnology
    Depositing user: Pure Administrator
    Date deposited:13 Mar 2017 12:53
    Last modified:11 Nov 2024 11:39
    URI:https://strathprints.strath.ac.uk/id/eprint/60153
CORE (COnnecting REpositories)