Asymmetric β-Methylation of l- and d-α-Amino Acids by a Self-Contained Enzyme Cascade

This report describes a modular enzyme-catalyzed cascade reaction that transforms l- or d-alpha-amino acids to beta-methyl-alpha-amino acids. In this process an alpha-amino acid transaminase, an alpha-keto acid methyltransferase, and a halide methyltransferase cooperate in two orthogonal reaction cycles that mediate product formation and regeneration of the cofactor pyridoxal-5 '-phosphate and the co-substrate S-adenosylmethionine. The only stoichiometric reagents consumed in this process are the unprotected l- or d-alpha-amino acid and methyl iodide.