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A bicyclic <i>S</i>-adenosylmethionine regeneration system applicable with different nucleosides or nucleotides as cofactor building blocks

Désirée Popadić, Dipali Mhaindarkar, Mike H. N. Dang Thai, Helen C. Hailes, Silja Mordhorst, Jennifer N. Andexer

2021RSC Chemical Biology56 citationsDOIOpen Access PDF

Abstract

-methylmethionine as methyl donor and a surplus of inorganic polyphosphate, along with catalytic amounts of l-methionine and cofactor building block reaching conversions of up to 99% (up to 200 turnovers). We also show that the cycle can be run with cofactor building blocks containing different purine and pyrimidine nucleobases, which can be fed in at the nucleoside or nucleotide stage. These alternative cofactors are in turn converted to the corresponding SAM analogues, which are considered to be a key for the development of bioorthogonal systems. In addition to purified enzymes, the bicyclic system can also be used with crude lysates highlighting its broad biocatalytic applicability.

Topics & Concepts

CofactorBioorthogonal chemistryBicyclic moleculeChemistryNucleosideBiocatalysisNucleotideNucleobaseBiochemistryCombinatorial chemistryEnzymeStereochemistryCatalysisDNAReaction mechanismGeneClick chemistryCancer-related gene regulationEpigenetics and DNA MethylationFolate and B Vitamins Research