Structural highlights
Function[COUO_STRRH] Mediates C-methylation at the 8-position of the aminocoumarin moieties in coumermycin A1 in the biosynthetic pathway of coumermycin antibiotic. Active on both mono- and bis-amides for mono- and di-C-methylation adjacent to the phenolic hydroxyl before it is glycosylated by CouM.[1] Publication Abstract from PubMedFriedel-Crafts alkylation of aromatic systems is a classic reaction in organic chemistry, for which regiospecific mono-alkylation, however, is generally difficult to achieve. In nature, methyltransferases catalyze the addition of methyl groups to a wide range of biomolecules thereby modulating the physico-chemical properties of these compounds. Specifically, S-adenosyl-L-methionine dependent C-methyltransferases possess a high potential to serve as biocatalysts in environmentally benign organic syntheses. Here, we report on the high resolution crystal structure of CouO, a C-methyltransferase from Streptomyces rishiriensis involved in the biosynthesis of the antibiotic coumermycin A1. Through molecular docking calculations, site-directed mutagenesis and the comparison with homologous enzymes we identified His120 and Arg121 as key functional residues for the enzymatic activity of this group of C-methyltransferases. The elucidation of the atomic structure and the insight into the catalytic mechanism provide the basis for the (semi)-rational engineering of the enzyme in order to increase the substrate scope as well as to facilitate the acceptance of SAM-analogues as alternative cofactors. Crystal Structure and Catalytic Mechanism of CouO, a Versatile C-Methyltransferase from Streptomyces rishiriensis.,Pavkov-Keller T, Steiner K, Faber M, Tengg M, Schwab H, Gruber-Khadjawi M, Gruber K PLoS One. 2017 Feb 2;12(2):e0171056. doi: 10.1371/journal.pone.0171056., eCollection 2017. PMID:28152088[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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