101601-14-3Relevant academic research and scientific papers
A Tandem Enzymatic sp2-C-Methylation Process: Coupling in Situ S-Adenosyl-l-Methionine Formation with Methyl Transfer
Sadler, Joanna C.,Humphreys, Luke D.,Snajdrova, Radka,Burley, Glenn A.
, p. 992 - 995 (2017)
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 labelled 13CH3, 13CD3 and CD3 groups from their corresponding SAM analogues formed in situ.
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.
