title: A Tandem Enzymatic sp2-C-Methylation Process: Coupling in Situ S-Adenosyl-l-Methionine Formation with Methyl Transfer.
abstract: A one-pot, two-step biocatalytic platform for the regiospecfic C-methylation and C-ethylation of aromatic substrates is described. The tandem process utilises SalL (Salinospora tropica) for in situ synthesis of S-adenosyl-l-methionine (SAM), followed by alkylation of aromatic substrates by the C-methyltransferase NovO (Streptomyces spheroides). The application of this methodology is demonstrated for the regiospecific labelling of aromatic substrates by the transfer of methyl, ethyl and isotopically labelled13CH3,13CD3and CD3groups from their corresponding SAM analogues formed in situ.
authors.affiliation: GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, SG1 2NY, UK.|WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL, UK.
authors.forename: Joanna C
authors.identifier: 0000-0002-8442-0760
authors.initials: JC
authors.lastname: Sadler
authors.affiliation: GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, SG1 2NY, UK.|Present address: Gilead Alberta ULC, 1021 Hayter Road NW, Edmonton, AB, T6S 1A1, Canada.
authors.forename: Luke D
authors.initials: LD
authors.lastname: Humphreys
authors.affiliation: GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, SG1 2NY, UK.
authors.forename: Radka
authors.initials: R
authors.lastname: Snajdrova
authors.affiliation: WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL, UK.
authors.forename: Glenn A
authors.identifier: 0000-0002-4896-113X
authors.initials: GA
authors.lastname: Burley
mesh_terms: D000478:Alkylation; D059001:Aquatic Organisms; D001419:Bacteria / Q000201:enzymology / Q000378:metabolism; D055162:Biocatalysis; D000072471:Heterocyclic Compounds, Fused-Ring / Q000378:metabolism; D006841:Hydrocarbons, Aromatic / Q000378:metabolism; D007553:Isotope Labeling; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000378:metabolism*
chemical_list: D000072471:Heterocyclic Compounds, Fused-Ring; D006841:Hydrocarbons, Aromatic; D012436:S-Adenosylmethionine; D008780:Methyltransferases
keywords: S-adenosylmethionine; alkylation; biocatalysis; methyltransferase; multi-enzyme reaction