Structural highlights
Function
[NOVO_STRNV] C-methyltransferase that methylates 8-demethylnovobiocic acid to produce novobiocic acid in the novobiocin biosynthesis pathway. Novobiocin is an aminocoumarin family antibiotic that targets bacterial DNA gyrases.[1]
Publication Abstract from PubMed
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.
Structural and Functional Basis of C-Methylation of Coumarin Scaffolds by NovO.,Sadler JC, Chung CH, Mosley JE, Burley GA, Humphreys LD ACS Chem Biol. 2017 Jan 13. doi: 10.1021/acschembio.6b01053. PMID:28068060[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Pacholec M, Tao J, Walsh CT. CouO and NovO: C-methyltransferases for tailoring the aminocoumarin scaffold in coumermycin and novobiocin antibiotic biosynthesis. Biochemistry. 2005 Nov 15;44(45):14969-76. PMID:16274243 doi:http://dx.doi.org/10.1021/bi051599o
- ↑ Sadler JC, Chung CH, Mosley JE, Burley GA, Humphreys LD. Structural and Functional Basis of C-Methylation of Coumarin Scaffolds by NovO. ACS Chem Biol. 2017 Jan 13. doi: 10.1021/acschembio.6b01053. PMID:28068060 doi:http://dx.doi.org/10.1021/acschembio.6b01053
