Structural and Functional Basis of C-Methylation of Coumarin Scaffolds by NovO.

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.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Sadler JC,Chung CH,Mosley JE,Burley GA,Humphreys LD

doi

10.1021/acschembio.6b01053

subject

Has Abstract

pub_date

2017-02-17 00:00:00

pages

374-379

issue

2

eissn

1554-8929

issn

1554-8937

journal_volume

12

pub_type

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