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

Joanna C. Sadler, Chun-wa H. Chung, Julie E. Mosley, Glenn A. Burley, Luke D. Humphreys

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)374-379
JournalAcs chemical biology
Issue number2
Early online date13 Jan 2017
Publication statusPublished - 17 Feb 2017


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