1374669-68-7Relevant articles and documents
S-Adenosyl Methionine Cofactor Modifications Enhance the Biocatalytic Repertoire of Small Molecule C-Alkylation
McKean, Iain J. W.,Sadler, Joanna C.,Cuetos, Anibal,Frese, Amina,Humphreys, Luke D.,Grogan, Gideon,Hoskisson, Paul A.,Burley, Glenn A.
supporting information, p. 17583 - 17588 (2019/11/11)
A tandem enzymatic strategy to enhance the scope of C-alkylation of small molecules via the in situ formation of S-adenosyl methionine (SAM) cofactor analogues is described. A solvent-exposed channel present in the SAM-forming enzyme SalL tolerates 5′-chloro-5′-deoxyadenosine (ClDA) analogues modified at the 2-position of the adenine nucleobase. Coupling SalL-catalyzed cofactor production with C-(m)ethyl transfer to coumarin substrates catalyzed by the methyltransferase (MTase) NovO forms C-(m)ethylated coumarins in superior yield and greater substrate scope relative to that obtained using cofactors lacking nucleobase modifications. Establishing the molecular determinants that influence C-alkylation provides the basis to develop a late-stage enzymatic platform for the preparation of high value small molecules.
