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 Bioljournal_title
ACS chemical biologyauthors
Sadler JC,Chung CH,Mosley JE,Burley GA,Humphreys LDdoi
10.1021/acschembio.6b01053subject
Has Abstractpub_date
2017-02-17 00:00:00pages
374-379issue
2eissn
1554-8929issn
1554-8937journal_volume
12pub_type
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