Chemoenzymatic synthesis and utilization of a SAM analog with an isomorphic nucleobase.

SalL, an enzyme that catalyzes the synthesis of SAM from l-methionine and 5'-chloro-5'-deoxyoadenosine, is shown to accept 5'-chloro-5'-deoxythienoadenosine as a substrate and facilitate the synthesis of a synthetic SAM analog with an unnatural nucleobase. This synthetic cofactor is demonstrated to replace SAM in the DNA methylation reaction with M.TaqI.