S-Adenosyl Methionine Cofactor Modifications Enhance the Biocatalytic Repertoire of Small Molecule C-Alkylation
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.
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)
Biocatalytic Friedel-Crafts alkylation using non-natural cofactors
A novel biocatalytic protocol for C -C bond formation is described and is an equivalent to Friedel-Crafts alkylation. S-Adenosyl-L-methionine (SAM), the major Chemical Equation Presentation methyl donor for biological methylation catalyzed by methyltransferases (Mtases), can perform alkylations (see scheme). These enzymes can accept non-natural cofactors and transfer functionalities other than methyl onto aromatic substrates
Stecher, Harald,Tengg, Martin,Ueberbacher, Bernhard J.,Remler, Peter,Schwab, Helmut,Griengl, Herfried,Gruber-Khadjawi, Mandona
supporting information; experimental part
p. 9546 - 9548
(2010/03/25)
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